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Test Lp(a) levels to inform ASCVD management: NLA statement
Lipoprotein(a) (Lp[a]) levels should be measured in clinical practice to refine risk prediction for atherosclerotic cardiovascular disease (ASCVD) and inform treatment decisions, even if they cannot yet be lowered directly, recommends the National Lipid Association (NLA) in a scientific statement.
The statement was published in the Journal of Clinical Lipidology.
Don P. Wilson, MD, department of pediatric endocrinology and diabetes, Cook Children’s Medical Center, Fort Worth, Tex., told this news organization that lipoprotein(a) is a “very timely subject.”
“The question in the scientific community is: What role does that particular biomarker play in terms of causing serious heart disease, stroke, and calcification of the aortic valve?”
“It’s pretty clear that, in and of itself, it actually can contribute and or cause any of those conditions,” he added. “The thing that’s then sort of problematic is that we don’t have a specific treatment to lower” Lp(a).
However, Dr. Wilson said that the statement underlines it is “still worth knowing” an individual’s Lp(a) concentrations because the risk with increased levels is “even higher for those people who have other conditions, such as metabolic disease or diabetes or high cholesterol.”
There are nevertheless several drugs in phase 2 and 3 clinical trials that appear to have the potential to significantly lower Lp(a) levels.
“I’m very excited,” said Dr. Wilson, noting that, so far, the drugs seem to be “quite safe,” and the currently available data suggest that they can “reduce Lp(a) levels by about 90%, which is huge.”
“That’s better than any drug we’ve got on the market.”
He cautioned, however, that it is going to take time after the drugs are approved to see the real benefits and risks once they start being used in very large populations, given that raised Lp(a) concentrations are present in about 20% of the world population.
The publication of the NLA statement coincides with a similar one from the European Atherosclerosis Society presented at the European Society of Cardiology Congress 2022 on Aug. 29, and published simultaneously in the European Heart Journal.
Coauthor of the EAS statement, Alberico L. Catapano, MD, PhD, professor of pharmacology at the University of Milan, and past president of the EAS, said that there are many areas in which the two statements are “in complete agreement.”
“However, the spirit of the documents is different,” he continued, chief among them being that the EAS statement focuses on the “global risk” of ASCVD and provides a risk calculator to help balance the risk increase with Lp(a) with that from other factors.
Another is that increased Lp(a) levels are recognized as being on a continuum in terms of their risk, such that there is no level at which raised concentrations can be deemed safe.
Dr. Wilson agreed with Dr. Capatano’s assessment, saying that the EAS statement takes current scientific observations “a step further,” in part by emphasizing that Lp(a) is “only one piece of the puzzle” for determining an individuals’ cardiovascular risk.
This will have huge implications for the conversations clinicians have with patients over shared decision-making, Dr. Wilson added.
Nevertheless, Dr. Catapano underlined to this news organization that “both documents are very important” in terms of the need to “raise awareness about a causal risk factor” for cardiovascular disease as well as that modifying Lp(a) concentrations “will probably reduce the risk.”
The statement from the NLA builds on the association’s prior Recommendations for the Patient-Centered Management of Dyslipidemia, published in two parts in 2014 and 2015, and comes to many of the same conclusions as the EAS statement.
It explains that apolipoprotein A, a component of Lp(a) attached to apolipoprotein B, has “unique” properties that promote the “initiation and progression of atherosclerosis and calcific valvular aortic stenosis, through endothelial dysfunction and proinflammatory responses, and pro-osteogenic effects promoting calcification.”
This, in turn, has the potential to cause myocardial infarction and ischemic stroke, the authors note.
This has been confirmed in meta-analyses of prospective, population-based studies showing a high risk for MI, coronary heart disease, and ischemic stroke with high Lp(a) levels, the statement adds.
Moreover, large genetic studies have confirmed that Lp(a) is a causal factor, independent of low-density lipoprotein cholesterol levels, for MI, ischemic stroke, valvular aortic stenosis, coronary artery stenosis, carotid stenosis, femoral artery stenosis, heart failure, cardiovascular mortality, and all-cause mortality.
Like the authors of the EAS statement, the NLA statement authors underline that the measurement of Lp(a) is “currently not standardized or harmonized,” and there is insufficient evidence on the utility of different cut-offs for risk based on age, gender, ethnicity, or the presence of comorbid conditions.
However, they do suggest that Lp(a) levels greater than 50 mg/dL (> 100 nmol/L) may be considered as a risk-enhancing factor favoring the initiation of statin therapy, although they note that the threshold could be threefold higher in African American individuals.
Despite these reservations, the authors say that Lp(a) testing “is reasonable” for refining the risk assessment of ASCVD in the first-degree relatives of people with premature ASCVD and those with a personal history of premature disease as well as in individuals with primary severe hypercholesterolemia.
Testing also “may be reasonable” to “aid in the clinician-patient discussion about whether to prescribe a statin” in people aged 40-75 years with borderline 10-year ASCVD risk, defined as 5%-7.4%, as well as in other equivocal clinical situations.
In terms of what to do in an individual with raised Lp(a) levels, the statement notes that lifestyle therapy and statins do not decrease Lp(a).
Although lomitapide (Juxtapid) and proprotein convertase subtilisin–kexin type 9 (PCSK9) inhibitors both lower levels of the lipoprotein, the former is “not recommended for ASCVD risk reduction,” whereas the impact of the latter on ASCVD risk reduction via Lp(a) reduction “remains undetermined.”
Several experimental agents are currently under investigation to reduce Lp(a) levels, including SLN360 (Silence Therapeutics), and AKCEA-APO(a)-LRX (Akcea Therapeutics/Ionis Pharmaceuticals).
In the meantime, the authors say it is reasonable to use Lp(a) as a “risk-enhancing factor” for the initiation of moderate- or high-intensity statins in the primary prevention of ASCVD and to consider the addition of ezetimibe and/or PCSK9 inhibitors in high- and very high–risk patients already on maximally tolerated statin therapy.
Finally, the authors recognize the need for “additional evidence” to support clinical practice. In the absence of a randomized clinical trial of Lp(a) lowering in those who are at risk for ASCVD, they note that “several important unanswered questions remain.”
These include: “Is it reasonable to recommend universal testing of Lp(a) in everyone regardless of family history or health status at least once to help encourage healthy habits and inform clinical decision-making?” “Will earlier testing and effective interventions help to improve outcomes?”
Alongside more evidence in children, the authors also emphasize that “additional data are urgently needed in Blacks, South Asians, and those of Hispanic descent.”
No funding declared. Dr. Wilson declares relationships with Osler Institute, Merck Sharp & Dohm, Novo Nordisk, and Alexion Pharmaceuticals. Other authors also declare numerous relationships. Dr. Catapano declares a relationship with Novartis.
A version of this article first appeared on Medscape.com.
Lipoprotein(a) (Lp[a]) levels should be measured in clinical practice to refine risk prediction for atherosclerotic cardiovascular disease (ASCVD) and inform treatment decisions, even if they cannot yet be lowered directly, recommends the National Lipid Association (NLA) in a scientific statement.
The statement was published in the Journal of Clinical Lipidology.
Don P. Wilson, MD, department of pediatric endocrinology and diabetes, Cook Children’s Medical Center, Fort Worth, Tex., told this news organization that lipoprotein(a) is a “very timely subject.”
“The question in the scientific community is: What role does that particular biomarker play in terms of causing serious heart disease, stroke, and calcification of the aortic valve?”
“It’s pretty clear that, in and of itself, it actually can contribute and or cause any of those conditions,” he added. “The thing that’s then sort of problematic is that we don’t have a specific treatment to lower” Lp(a).
However, Dr. Wilson said that the statement underlines it is “still worth knowing” an individual’s Lp(a) concentrations because the risk with increased levels is “even higher for those people who have other conditions, such as metabolic disease or diabetes or high cholesterol.”
There are nevertheless several drugs in phase 2 and 3 clinical trials that appear to have the potential to significantly lower Lp(a) levels.
“I’m very excited,” said Dr. Wilson, noting that, so far, the drugs seem to be “quite safe,” and the currently available data suggest that they can “reduce Lp(a) levels by about 90%, which is huge.”
“That’s better than any drug we’ve got on the market.”
He cautioned, however, that it is going to take time after the drugs are approved to see the real benefits and risks once they start being used in very large populations, given that raised Lp(a) concentrations are present in about 20% of the world population.
The publication of the NLA statement coincides with a similar one from the European Atherosclerosis Society presented at the European Society of Cardiology Congress 2022 on Aug. 29, and published simultaneously in the European Heart Journal.
Coauthor of the EAS statement, Alberico L. Catapano, MD, PhD, professor of pharmacology at the University of Milan, and past president of the EAS, said that there are many areas in which the two statements are “in complete agreement.”
“However, the spirit of the documents is different,” he continued, chief among them being that the EAS statement focuses on the “global risk” of ASCVD and provides a risk calculator to help balance the risk increase with Lp(a) with that from other factors.
Another is that increased Lp(a) levels are recognized as being on a continuum in terms of their risk, such that there is no level at which raised concentrations can be deemed safe.
Dr. Wilson agreed with Dr. Capatano’s assessment, saying that the EAS statement takes current scientific observations “a step further,” in part by emphasizing that Lp(a) is “only one piece of the puzzle” for determining an individuals’ cardiovascular risk.
This will have huge implications for the conversations clinicians have with patients over shared decision-making, Dr. Wilson added.
Nevertheless, Dr. Catapano underlined to this news organization that “both documents are very important” in terms of the need to “raise awareness about a causal risk factor” for cardiovascular disease as well as that modifying Lp(a) concentrations “will probably reduce the risk.”
The statement from the NLA builds on the association’s prior Recommendations for the Patient-Centered Management of Dyslipidemia, published in two parts in 2014 and 2015, and comes to many of the same conclusions as the EAS statement.
It explains that apolipoprotein A, a component of Lp(a) attached to apolipoprotein B, has “unique” properties that promote the “initiation and progression of atherosclerosis and calcific valvular aortic stenosis, through endothelial dysfunction and proinflammatory responses, and pro-osteogenic effects promoting calcification.”
This, in turn, has the potential to cause myocardial infarction and ischemic stroke, the authors note.
This has been confirmed in meta-analyses of prospective, population-based studies showing a high risk for MI, coronary heart disease, and ischemic stroke with high Lp(a) levels, the statement adds.
Moreover, large genetic studies have confirmed that Lp(a) is a causal factor, independent of low-density lipoprotein cholesterol levels, for MI, ischemic stroke, valvular aortic stenosis, coronary artery stenosis, carotid stenosis, femoral artery stenosis, heart failure, cardiovascular mortality, and all-cause mortality.
Like the authors of the EAS statement, the NLA statement authors underline that the measurement of Lp(a) is “currently not standardized or harmonized,” and there is insufficient evidence on the utility of different cut-offs for risk based on age, gender, ethnicity, or the presence of comorbid conditions.
However, they do suggest that Lp(a) levels greater than 50 mg/dL (> 100 nmol/L) may be considered as a risk-enhancing factor favoring the initiation of statin therapy, although they note that the threshold could be threefold higher in African American individuals.
Despite these reservations, the authors say that Lp(a) testing “is reasonable” for refining the risk assessment of ASCVD in the first-degree relatives of people with premature ASCVD and those with a personal history of premature disease as well as in individuals with primary severe hypercholesterolemia.
Testing also “may be reasonable” to “aid in the clinician-patient discussion about whether to prescribe a statin” in people aged 40-75 years with borderline 10-year ASCVD risk, defined as 5%-7.4%, as well as in other equivocal clinical situations.
In terms of what to do in an individual with raised Lp(a) levels, the statement notes that lifestyle therapy and statins do not decrease Lp(a).
Although lomitapide (Juxtapid) and proprotein convertase subtilisin–kexin type 9 (PCSK9) inhibitors both lower levels of the lipoprotein, the former is “not recommended for ASCVD risk reduction,” whereas the impact of the latter on ASCVD risk reduction via Lp(a) reduction “remains undetermined.”
Several experimental agents are currently under investigation to reduce Lp(a) levels, including SLN360 (Silence Therapeutics), and AKCEA-APO(a)-LRX (Akcea Therapeutics/Ionis Pharmaceuticals).
In the meantime, the authors say it is reasonable to use Lp(a) as a “risk-enhancing factor” for the initiation of moderate- or high-intensity statins in the primary prevention of ASCVD and to consider the addition of ezetimibe and/or PCSK9 inhibitors in high- and very high–risk patients already on maximally tolerated statin therapy.
Finally, the authors recognize the need for “additional evidence” to support clinical practice. In the absence of a randomized clinical trial of Lp(a) lowering in those who are at risk for ASCVD, they note that “several important unanswered questions remain.”
These include: “Is it reasonable to recommend universal testing of Lp(a) in everyone regardless of family history or health status at least once to help encourage healthy habits and inform clinical decision-making?” “Will earlier testing and effective interventions help to improve outcomes?”
Alongside more evidence in children, the authors also emphasize that “additional data are urgently needed in Blacks, South Asians, and those of Hispanic descent.”
No funding declared. Dr. Wilson declares relationships with Osler Institute, Merck Sharp & Dohm, Novo Nordisk, and Alexion Pharmaceuticals. Other authors also declare numerous relationships. Dr. Catapano declares a relationship with Novartis.
A version of this article first appeared on Medscape.com.
Lipoprotein(a) (Lp[a]) levels should be measured in clinical practice to refine risk prediction for atherosclerotic cardiovascular disease (ASCVD) and inform treatment decisions, even if they cannot yet be lowered directly, recommends the National Lipid Association (NLA) in a scientific statement.
The statement was published in the Journal of Clinical Lipidology.
Don P. Wilson, MD, department of pediatric endocrinology and diabetes, Cook Children’s Medical Center, Fort Worth, Tex., told this news organization that lipoprotein(a) is a “very timely subject.”
“The question in the scientific community is: What role does that particular biomarker play in terms of causing serious heart disease, stroke, and calcification of the aortic valve?”
“It’s pretty clear that, in and of itself, it actually can contribute and or cause any of those conditions,” he added. “The thing that’s then sort of problematic is that we don’t have a specific treatment to lower” Lp(a).
However, Dr. Wilson said that the statement underlines it is “still worth knowing” an individual’s Lp(a) concentrations because the risk with increased levels is “even higher for those people who have other conditions, such as metabolic disease or diabetes or high cholesterol.”
There are nevertheless several drugs in phase 2 and 3 clinical trials that appear to have the potential to significantly lower Lp(a) levels.
“I’m very excited,” said Dr. Wilson, noting that, so far, the drugs seem to be “quite safe,” and the currently available data suggest that they can “reduce Lp(a) levels by about 90%, which is huge.”
“That’s better than any drug we’ve got on the market.”
He cautioned, however, that it is going to take time after the drugs are approved to see the real benefits and risks once they start being used in very large populations, given that raised Lp(a) concentrations are present in about 20% of the world population.
The publication of the NLA statement coincides with a similar one from the European Atherosclerosis Society presented at the European Society of Cardiology Congress 2022 on Aug. 29, and published simultaneously in the European Heart Journal.
Coauthor of the EAS statement, Alberico L. Catapano, MD, PhD, professor of pharmacology at the University of Milan, and past president of the EAS, said that there are many areas in which the two statements are “in complete agreement.”
“However, the spirit of the documents is different,” he continued, chief among them being that the EAS statement focuses on the “global risk” of ASCVD and provides a risk calculator to help balance the risk increase with Lp(a) with that from other factors.
Another is that increased Lp(a) levels are recognized as being on a continuum in terms of their risk, such that there is no level at which raised concentrations can be deemed safe.
Dr. Wilson agreed with Dr. Capatano’s assessment, saying that the EAS statement takes current scientific observations “a step further,” in part by emphasizing that Lp(a) is “only one piece of the puzzle” for determining an individuals’ cardiovascular risk.
This will have huge implications for the conversations clinicians have with patients over shared decision-making, Dr. Wilson added.
Nevertheless, Dr. Catapano underlined to this news organization that “both documents are very important” in terms of the need to “raise awareness about a causal risk factor” for cardiovascular disease as well as that modifying Lp(a) concentrations “will probably reduce the risk.”
The statement from the NLA builds on the association’s prior Recommendations for the Patient-Centered Management of Dyslipidemia, published in two parts in 2014 and 2015, and comes to many of the same conclusions as the EAS statement.
It explains that apolipoprotein A, a component of Lp(a) attached to apolipoprotein B, has “unique” properties that promote the “initiation and progression of atherosclerosis and calcific valvular aortic stenosis, through endothelial dysfunction and proinflammatory responses, and pro-osteogenic effects promoting calcification.”
This, in turn, has the potential to cause myocardial infarction and ischemic stroke, the authors note.
This has been confirmed in meta-analyses of prospective, population-based studies showing a high risk for MI, coronary heart disease, and ischemic stroke with high Lp(a) levels, the statement adds.
Moreover, large genetic studies have confirmed that Lp(a) is a causal factor, independent of low-density lipoprotein cholesterol levels, for MI, ischemic stroke, valvular aortic stenosis, coronary artery stenosis, carotid stenosis, femoral artery stenosis, heart failure, cardiovascular mortality, and all-cause mortality.
Like the authors of the EAS statement, the NLA statement authors underline that the measurement of Lp(a) is “currently not standardized or harmonized,” and there is insufficient evidence on the utility of different cut-offs for risk based on age, gender, ethnicity, or the presence of comorbid conditions.
However, they do suggest that Lp(a) levels greater than 50 mg/dL (> 100 nmol/L) may be considered as a risk-enhancing factor favoring the initiation of statin therapy, although they note that the threshold could be threefold higher in African American individuals.
Despite these reservations, the authors say that Lp(a) testing “is reasonable” for refining the risk assessment of ASCVD in the first-degree relatives of people with premature ASCVD and those with a personal history of premature disease as well as in individuals with primary severe hypercholesterolemia.
Testing also “may be reasonable” to “aid in the clinician-patient discussion about whether to prescribe a statin” in people aged 40-75 years with borderline 10-year ASCVD risk, defined as 5%-7.4%, as well as in other equivocal clinical situations.
In terms of what to do in an individual with raised Lp(a) levels, the statement notes that lifestyle therapy and statins do not decrease Lp(a).
Although lomitapide (Juxtapid) and proprotein convertase subtilisin–kexin type 9 (PCSK9) inhibitors both lower levels of the lipoprotein, the former is “not recommended for ASCVD risk reduction,” whereas the impact of the latter on ASCVD risk reduction via Lp(a) reduction “remains undetermined.”
Several experimental agents are currently under investigation to reduce Lp(a) levels, including SLN360 (Silence Therapeutics), and AKCEA-APO(a)-LRX (Akcea Therapeutics/Ionis Pharmaceuticals).
In the meantime, the authors say it is reasonable to use Lp(a) as a “risk-enhancing factor” for the initiation of moderate- or high-intensity statins in the primary prevention of ASCVD and to consider the addition of ezetimibe and/or PCSK9 inhibitors in high- and very high–risk patients already on maximally tolerated statin therapy.
Finally, the authors recognize the need for “additional evidence” to support clinical practice. In the absence of a randomized clinical trial of Lp(a) lowering in those who are at risk for ASCVD, they note that “several important unanswered questions remain.”
These include: “Is it reasonable to recommend universal testing of Lp(a) in everyone regardless of family history or health status at least once to help encourage healthy habits and inform clinical decision-making?” “Will earlier testing and effective interventions help to improve outcomes?”
Alongside more evidence in children, the authors also emphasize that “additional data are urgently needed in Blacks, South Asians, and those of Hispanic descent.”
No funding declared. Dr. Wilson declares relationships with Osler Institute, Merck Sharp & Dohm, Novo Nordisk, and Alexion Pharmaceuticals. Other authors also declare numerous relationships. Dr. Catapano declares a relationship with Novartis.
A version of this article first appeared on Medscape.com.
New ESC cardio-oncology guideline aims to reduce cardiotoxicity
BARCELONA – Cardiovascular disease risk factors, as well as established disease, in patients undergoing cancer therapy can be safely managed to minimize cancer therapy–related cardiovascular toxicity (CVR-CVT), conclude the first cardio-oncology guidelines from the European Society of Cardiology.
The guidelines were presented at the annual congress of the European Society of Cardiology and published simultaneously in the European Heart Journal.
Guideline cochair Alexander R. Lyon, MD, PhD, told this news organization that the aim of the guideline was to “personalize the decision-making of a patient with cancer who has cardiovascular disease or is at risk of developing it from their treatment ... because it’s not one size fits all.”
because how you manage someone who’s at high risk is going to be different” than managing someone who is at moderate or low risk, he said.
“We’re doing a lot of surveillance because one of the big advantages of cardio-oncology is we know when someone is about to get treated,” Dr. Lyon, from the National Heart and Lung Institute, Imperial College London, and Cardio-Oncology Service, Royal Brompton Hospital, London, said.
“You don’t know in nature when someone’s going to have an acute myocardial infarction or acute viral myocarditis, but we do know when they’re coming into an oncology clinic to get an infusion of chemotherapy or tablets,” he noted.
The guidelines offer recommendations so that patients can “have their treatment safely and minimize interruptions.”
“We know these cancer therapies work; we’re here to get the best of both worlds” by minimizing cardiotoxicity, Dr. Lyon said.
Steady decline in cancer-related mortality
The guidelines note that since the 1990s there has been a “steady decline in cancer-related mortality, mirrored by a steady increase in cancer survival,” and the result is that “treatment-related side effects have gained more significance.”
Dr. Lyon said that between 2011 and 2021, there was a fivefold increase in the number of new referrals of cancer patients with cardiological consequences to his institution.
He said that one of main drivers is modifiable factors, such as smoking, obesity, and inactivity, which increase the risk for both cancer and cardiovascular disease.
“Allied to that, there’s been an improvement in treating cardiovascular diseases in people in their 40s, 50s, and 60s, so they’re surviving their heart failure, myocardial infarction, atrial fibrillation to develop cancers in later life.”
Combined with the aging population, the result is that “not only are many more people being diagnosed with cancer, because they’re living longer, but they have all these pre-existing heart risk factors, whether as confirmed disease or just the risk factors associated with that,” he said.
Another aspect is that many of the newer, targeted cancer therapies confer a cardiovascular risk.
Dr. Lyon said that the “most famous one” is trastuzumab, a monoclonal antibody that is used to treat HER2-positive breast cancer but that also causes left ventricular impairment “in about 15%-20% of the women taking it and can cause severe heart failure if it is missed.”
That, he continued, was the “forerunner of designer, targeted therapies,” and the subsequent “explosion” in the availability of modern cancer therapies has included many that confer cardiac issues.
The final reason for the greater interest in cardio-oncology, Dr. Lyon added, is the increasing awareness in oncology and hematology teams of the potential for cardiac problems among their patients.
“We have been reaching out to our oncology and hematology colleagues over the last 5-10 years to explain we’re here to help. We’re not here to stop their treatments, we’re here to support them.”
Presenting the guidelines, cochair Teresa López-Fernández, MD, cardiology department, La Paz University Hospital, IdiPAZ Research Institute, Madrid, said that the “spectrum of CVR-CVT presentations” includes arterial hypertension, cardiac arrhythmias, coronary artery disease, heart failure, and myocarditis.
She explained that cytotoxic cancer therapies are associated with an increased risk for cardiac toxicity that is most acute during the treatment phase but is not entirely diminished once it is over, then typically accumulates during long-term follow-up.
Crucially, the impact of cancer therapy on cardiovascular risk is dependent on several factors, such as patient age, cancer history, pre-existing cardiovascular risk factors or cardiovascular disease, and previous cardiotoxic cancer therapy.
There are nevertheless a number of potential strategies to reduce the risk for cardiac toxicity, including primary and secondary prevention prior to the start of cancer therapy and early CVR-CVT management during treatment, as well as cardiovascular risk assessment in the first year after treatment completion and cancer-survivorship programs.
To those ends, Dr. López-Fernández said the guidelines incorporate 272 new recommendations that cover the entire cardio-oncology care pathway, beginning with cardiovascular risk stratification before anticancer therapy.
They offer a risk-assessment checklist and make a series of recommendations for patients to be treated with potentially cardiotoxic drugs, such as anthracyclines, as well as recommendations on cardiac imaging.
The guidelines provide a range of recommendations for primary and secondary cancer therapy–related cardiovascular toxicity prevention, including minimization of the use of cardiotoxic drugs and the use of angiotensin-converting-enzyme inhibitors, angiotensin-receptor blockers, beta blockers, and statins for primary prevention.
They establish CVR-CVT monitoring protocols across the gamut of cancer therapies, from HER-targeted therapies, through immune checkpoint inhibitors, Bruton tyrosine kinase, CDK4/6, EGFR, VEGF, and ALK inhibitors, and androgen-deprivation and endocrine therapies, to the more novel CAR-T-cell therapies.
A section on radiotherapy-induced cardiovascular toxicity has its own protocol for the establishment of an individual’s mean heart dose of radiation or the amount of radiation exposure to the heart during treatment.
Next, Dr. Lyon looked at recommendations for the management of cardiovascular disease and cancer therapy–related cardiovascular toxicity in patients receiving anticancer treatment.
He underlined that treatment decisions should consider the cancer and cardiovascular symptom burden, the cancer prognosis, the requirements for cancer treatment, including alternative options, drug-drug interactions, and patient preferences.
Dr. Lyon highlighted the algorithms designed to aid the management of cardiac dysfunction related to anthracycline chemotherapy, HER2-targeted therapy, and immune checkpoint inhibitors, as well as QTc-prolonging anticancer drugs.
In the first 12 months after the completions of therapy, there are a number of risk factors for future cardiovascular disease, he continued.
These include high and very high baseline cardiovascular toxicity risk, anticancer treatments known to have a high risk for long-term cardiovascular complications, such as doxorubicin and radiotherapy, and moderate or severe CTR-CVT during anticancer treatment.
Over the long term, the guidelines recommend that surveillance in asymptomatic cancer survivors range from an annual cardiovascular risk assessment in low-risk patients to patient education and cardiovascular risk factor optimization, alongside regular transthoracic echocardiography in high-risk groups.
Finally, Dr. Lyon said the guidelines turn their attention to special populations, such as patients with cardiac masses and tumors, those with carcinoid heart disease, pregnant women receiving cancer therapy, as well as those with cardiac implantable electronic devices undergoing radiotherapy.
The guidelines were developed by the task force on cardio-oncology of the ESC, in collaboration with the European Hematology Association, the European Society for Therapeutic Radiology and Oncology, and the International Cardio-Oncology Society. Dr. Lyon declares relationships with Akcea, Takeda Pharmaceuticals, Pfizer, GlaxoSmithKline, AstraZeneca, Novartis, Ferring Pharmaceuticals, Heartfelt Technologies, Brainstorm, and Myocardial Solutions. Dr. López-Fernández declares relationships with Daiichi Sankyo, Almirall Spain, Janssen-Cilag, Bayer, Roche, Philips, and Incyte.
A version of this article first appeared on Medscape.com.
BARCELONA – Cardiovascular disease risk factors, as well as established disease, in patients undergoing cancer therapy can be safely managed to minimize cancer therapy–related cardiovascular toxicity (CVR-CVT), conclude the first cardio-oncology guidelines from the European Society of Cardiology.
The guidelines were presented at the annual congress of the European Society of Cardiology and published simultaneously in the European Heart Journal.
Guideline cochair Alexander R. Lyon, MD, PhD, told this news organization that the aim of the guideline was to “personalize the decision-making of a patient with cancer who has cardiovascular disease or is at risk of developing it from their treatment ... because it’s not one size fits all.”
because how you manage someone who’s at high risk is going to be different” than managing someone who is at moderate or low risk, he said.
“We’re doing a lot of surveillance because one of the big advantages of cardio-oncology is we know when someone is about to get treated,” Dr. Lyon, from the National Heart and Lung Institute, Imperial College London, and Cardio-Oncology Service, Royal Brompton Hospital, London, said.
“You don’t know in nature when someone’s going to have an acute myocardial infarction or acute viral myocarditis, but we do know when they’re coming into an oncology clinic to get an infusion of chemotherapy or tablets,” he noted.
The guidelines offer recommendations so that patients can “have their treatment safely and minimize interruptions.”
“We know these cancer therapies work; we’re here to get the best of both worlds” by minimizing cardiotoxicity, Dr. Lyon said.
Steady decline in cancer-related mortality
The guidelines note that since the 1990s there has been a “steady decline in cancer-related mortality, mirrored by a steady increase in cancer survival,” and the result is that “treatment-related side effects have gained more significance.”
Dr. Lyon said that between 2011 and 2021, there was a fivefold increase in the number of new referrals of cancer patients with cardiological consequences to his institution.
He said that one of main drivers is modifiable factors, such as smoking, obesity, and inactivity, which increase the risk for both cancer and cardiovascular disease.
“Allied to that, there’s been an improvement in treating cardiovascular diseases in people in their 40s, 50s, and 60s, so they’re surviving their heart failure, myocardial infarction, atrial fibrillation to develop cancers in later life.”
Combined with the aging population, the result is that “not only are many more people being diagnosed with cancer, because they’re living longer, but they have all these pre-existing heart risk factors, whether as confirmed disease or just the risk factors associated with that,” he said.
Another aspect is that many of the newer, targeted cancer therapies confer a cardiovascular risk.
Dr. Lyon said that the “most famous one” is trastuzumab, a monoclonal antibody that is used to treat HER2-positive breast cancer but that also causes left ventricular impairment “in about 15%-20% of the women taking it and can cause severe heart failure if it is missed.”
That, he continued, was the “forerunner of designer, targeted therapies,” and the subsequent “explosion” in the availability of modern cancer therapies has included many that confer cardiac issues.
The final reason for the greater interest in cardio-oncology, Dr. Lyon added, is the increasing awareness in oncology and hematology teams of the potential for cardiac problems among their patients.
“We have been reaching out to our oncology and hematology colleagues over the last 5-10 years to explain we’re here to help. We’re not here to stop their treatments, we’re here to support them.”
Presenting the guidelines, cochair Teresa López-Fernández, MD, cardiology department, La Paz University Hospital, IdiPAZ Research Institute, Madrid, said that the “spectrum of CVR-CVT presentations” includes arterial hypertension, cardiac arrhythmias, coronary artery disease, heart failure, and myocarditis.
She explained that cytotoxic cancer therapies are associated with an increased risk for cardiac toxicity that is most acute during the treatment phase but is not entirely diminished once it is over, then typically accumulates during long-term follow-up.
Crucially, the impact of cancer therapy on cardiovascular risk is dependent on several factors, such as patient age, cancer history, pre-existing cardiovascular risk factors or cardiovascular disease, and previous cardiotoxic cancer therapy.
There are nevertheless a number of potential strategies to reduce the risk for cardiac toxicity, including primary and secondary prevention prior to the start of cancer therapy and early CVR-CVT management during treatment, as well as cardiovascular risk assessment in the first year after treatment completion and cancer-survivorship programs.
To those ends, Dr. López-Fernández said the guidelines incorporate 272 new recommendations that cover the entire cardio-oncology care pathway, beginning with cardiovascular risk stratification before anticancer therapy.
They offer a risk-assessment checklist and make a series of recommendations for patients to be treated with potentially cardiotoxic drugs, such as anthracyclines, as well as recommendations on cardiac imaging.
The guidelines provide a range of recommendations for primary and secondary cancer therapy–related cardiovascular toxicity prevention, including minimization of the use of cardiotoxic drugs and the use of angiotensin-converting-enzyme inhibitors, angiotensin-receptor blockers, beta blockers, and statins for primary prevention.
They establish CVR-CVT monitoring protocols across the gamut of cancer therapies, from HER-targeted therapies, through immune checkpoint inhibitors, Bruton tyrosine kinase, CDK4/6, EGFR, VEGF, and ALK inhibitors, and androgen-deprivation and endocrine therapies, to the more novel CAR-T-cell therapies.
A section on radiotherapy-induced cardiovascular toxicity has its own protocol for the establishment of an individual’s mean heart dose of radiation or the amount of radiation exposure to the heart during treatment.
Next, Dr. Lyon looked at recommendations for the management of cardiovascular disease and cancer therapy–related cardiovascular toxicity in patients receiving anticancer treatment.
He underlined that treatment decisions should consider the cancer and cardiovascular symptom burden, the cancer prognosis, the requirements for cancer treatment, including alternative options, drug-drug interactions, and patient preferences.
Dr. Lyon highlighted the algorithms designed to aid the management of cardiac dysfunction related to anthracycline chemotherapy, HER2-targeted therapy, and immune checkpoint inhibitors, as well as QTc-prolonging anticancer drugs.
In the first 12 months after the completions of therapy, there are a number of risk factors for future cardiovascular disease, he continued.
These include high and very high baseline cardiovascular toxicity risk, anticancer treatments known to have a high risk for long-term cardiovascular complications, such as doxorubicin and radiotherapy, and moderate or severe CTR-CVT during anticancer treatment.
Over the long term, the guidelines recommend that surveillance in asymptomatic cancer survivors range from an annual cardiovascular risk assessment in low-risk patients to patient education and cardiovascular risk factor optimization, alongside regular transthoracic echocardiography in high-risk groups.
Finally, Dr. Lyon said the guidelines turn their attention to special populations, such as patients with cardiac masses and tumors, those with carcinoid heart disease, pregnant women receiving cancer therapy, as well as those with cardiac implantable electronic devices undergoing radiotherapy.
The guidelines were developed by the task force on cardio-oncology of the ESC, in collaboration with the European Hematology Association, the European Society for Therapeutic Radiology and Oncology, and the International Cardio-Oncology Society. Dr. Lyon declares relationships with Akcea, Takeda Pharmaceuticals, Pfizer, GlaxoSmithKline, AstraZeneca, Novartis, Ferring Pharmaceuticals, Heartfelt Technologies, Brainstorm, and Myocardial Solutions. Dr. López-Fernández declares relationships with Daiichi Sankyo, Almirall Spain, Janssen-Cilag, Bayer, Roche, Philips, and Incyte.
A version of this article first appeared on Medscape.com.
BARCELONA – Cardiovascular disease risk factors, as well as established disease, in patients undergoing cancer therapy can be safely managed to minimize cancer therapy–related cardiovascular toxicity (CVR-CVT), conclude the first cardio-oncology guidelines from the European Society of Cardiology.
The guidelines were presented at the annual congress of the European Society of Cardiology and published simultaneously in the European Heart Journal.
Guideline cochair Alexander R. Lyon, MD, PhD, told this news organization that the aim of the guideline was to “personalize the decision-making of a patient with cancer who has cardiovascular disease or is at risk of developing it from their treatment ... because it’s not one size fits all.”
because how you manage someone who’s at high risk is going to be different” than managing someone who is at moderate or low risk, he said.
“We’re doing a lot of surveillance because one of the big advantages of cardio-oncology is we know when someone is about to get treated,” Dr. Lyon, from the National Heart and Lung Institute, Imperial College London, and Cardio-Oncology Service, Royal Brompton Hospital, London, said.
“You don’t know in nature when someone’s going to have an acute myocardial infarction or acute viral myocarditis, but we do know when they’re coming into an oncology clinic to get an infusion of chemotherapy or tablets,” he noted.
The guidelines offer recommendations so that patients can “have their treatment safely and minimize interruptions.”
“We know these cancer therapies work; we’re here to get the best of both worlds” by minimizing cardiotoxicity, Dr. Lyon said.
Steady decline in cancer-related mortality
The guidelines note that since the 1990s there has been a “steady decline in cancer-related mortality, mirrored by a steady increase in cancer survival,” and the result is that “treatment-related side effects have gained more significance.”
Dr. Lyon said that between 2011 and 2021, there was a fivefold increase in the number of new referrals of cancer patients with cardiological consequences to his institution.
He said that one of main drivers is modifiable factors, such as smoking, obesity, and inactivity, which increase the risk for both cancer and cardiovascular disease.
“Allied to that, there’s been an improvement in treating cardiovascular diseases in people in their 40s, 50s, and 60s, so they’re surviving their heart failure, myocardial infarction, atrial fibrillation to develop cancers in later life.”
Combined with the aging population, the result is that “not only are many more people being diagnosed with cancer, because they’re living longer, but they have all these pre-existing heart risk factors, whether as confirmed disease or just the risk factors associated with that,” he said.
Another aspect is that many of the newer, targeted cancer therapies confer a cardiovascular risk.
Dr. Lyon said that the “most famous one” is trastuzumab, a monoclonal antibody that is used to treat HER2-positive breast cancer but that also causes left ventricular impairment “in about 15%-20% of the women taking it and can cause severe heart failure if it is missed.”
That, he continued, was the “forerunner of designer, targeted therapies,” and the subsequent “explosion” in the availability of modern cancer therapies has included many that confer cardiac issues.
The final reason for the greater interest in cardio-oncology, Dr. Lyon added, is the increasing awareness in oncology and hematology teams of the potential for cardiac problems among their patients.
“We have been reaching out to our oncology and hematology colleagues over the last 5-10 years to explain we’re here to help. We’re not here to stop their treatments, we’re here to support them.”
Presenting the guidelines, cochair Teresa López-Fernández, MD, cardiology department, La Paz University Hospital, IdiPAZ Research Institute, Madrid, said that the “spectrum of CVR-CVT presentations” includes arterial hypertension, cardiac arrhythmias, coronary artery disease, heart failure, and myocarditis.
She explained that cytotoxic cancer therapies are associated with an increased risk for cardiac toxicity that is most acute during the treatment phase but is not entirely diminished once it is over, then typically accumulates during long-term follow-up.
Crucially, the impact of cancer therapy on cardiovascular risk is dependent on several factors, such as patient age, cancer history, pre-existing cardiovascular risk factors or cardiovascular disease, and previous cardiotoxic cancer therapy.
There are nevertheless a number of potential strategies to reduce the risk for cardiac toxicity, including primary and secondary prevention prior to the start of cancer therapy and early CVR-CVT management during treatment, as well as cardiovascular risk assessment in the first year after treatment completion and cancer-survivorship programs.
To those ends, Dr. López-Fernández said the guidelines incorporate 272 new recommendations that cover the entire cardio-oncology care pathway, beginning with cardiovascular risk stratification before anticancer therapy.
They offer a risk-assessment checklist and make a series of recommendations for patients to be treated with potentially cardiotoxic drugs, such as anthracyclines, as well as recommendations on cardiac imaging.
The guidelines provide a range of recommendations for primary and secondary cancer therapy–related cardiovascular toxicity prevention, including minimization of the use of cardiotoxic drugs and the use of angiotensin-converting-enzyme inhibitors, angiotensin-receptor blockers, beta blockers, and statins for primary prevention.
They establish CVR-CVT monitoring protocols across the gamut of cancer therapies, from HER-targeted therapies, through immune checkpoint inhibitors, Bruton tyrosine kinase, CDK4/6, EGFR, VEGF, and ALK inhibitors, and androgen-deprivation and endocrine therapies, to the more novel CAR-T-cell therapies.
A section on radiotherapy-induced cardiovascular toxicity has its own protocol for the establishment of an individual’s mean heart dose of radiation or the amount of radiation exposure to the heart during treatment.
Next, Dr. Lyon looked at recommendations for the management of cardiovascular disease and cancer therapy–related cardiovascular toxicity in patients receiving anticancer treatment.
He underlined that treatment decisions should consider the cancer and cardiovascular symptom burden, the cancer prognosis, the requirements for cancer treatment, including alternative options, drug-drug interactions, and patient preferences.
Dr. Lyon highlighted the algorithms designed to aid the management of cardiac dysfunction related to anthracycline chemotherapy, HER2-targeted therapy, and immune checkpoint inhibitors, as well as QTc-prolonging anticancer drugs.
In the first 12 months after the completions of therapy, there are a number of risk factors for future cardiovascular disease, he continued.
These include high and very high baseline cardiovascular toxicity risk, anticancer treatments known to have a high risk for long-term cardiovascular complications, such as doxorubicin and radiotherapy, and moderate or severe CTR-CVT during anticancer treatment.
Over the long term, the guidelines recommend that surveillance in asymptomatic cancer survivors range from an annual cardiovascular risk assessment in low-risk patients to patient education and cardiovascular risk factor optimization, alongside regular transthoracic echocardiography in high-risk groups.
Finally, Dr. Lyon said the guidelines turn their attention to special populations, such as patients with cardiac masses and tumors, those with carcinoid heart disease, pregnant women receiving cancer therapy, as well as those with cardiac implantable electronic devices undergoing radiotherapy.
The guidelines were developed by the task force on cardio-oncology of the ESC, in collaboration with the European Hematology Association, the European Society for Therapeutic Radiology and Oncology, and the International Cardio-Oncology Society. Dr. Lyon declares relationships with Akcea, Takeda Pharmaceuticals, Pfizer, GlaxoSmithKline, AstraZeneca, Novartis, Ferring Pharmaceuticals, Heartfelt Technologies, Brainstorm, and Myocardial Solutions. Dr. López-Fernández declares relationships with Daiichi Sankyo, Almirall Spain, Janssen-Cilag, Bayer, Roche, Philips, and Incyte.
A version of this article first appeared on Medscape.com.
Men at higher risk than are women for many cancers: Why?
Men have a significantly increased risk of developing 11 different cancers, and the risk is three times greater for men for certain cancers, including those of the esophagus, larynx, gastric cardia, and bladder.
But why?
“There are differences in cancer incidence that are not explained by environmental exposures alone,” said lead author Sarah S. Jackson, PhD, of the division of cancer epidemiology and genetics at the National Cancer Institute in Bethesda, Md.
“This suggests that there are intrinsic biological differences between men and women that affect susceptibility to cancer,” she added in a statement.
The study was published online in the journal Cancer.
“Understanding the sex-related biologic mechanisms that lead to the male predominance of cancer at shared anatomic sites could have important implications for etiology and prevention,” the researchers suggested.
In an interview, Dr. Jackson said that the results “do not support changes to existing cancer prevention protocol” to address the disparities in cancer rates between men and women.
“More research is needed before any recommendations can be made,” she told this news organization. “For example, we need more research on the female immune response. If we can discover the mechanisms by which females have an immune advantage, we may be able to develop therapeutics to bolster the immune system to prevent and treat cancer.
“We also should start reporting our findings on cancer incidence, screening, and survival by sex to ensure that we are not missing important sex-specific associations.”
Comprehensive analyses
The researchers “should be applauded” for their “thorough and comprehensive analyses,” said the authors of an accompanying editorial, Jingqin R. Luo, PhD, and Graham A. Colditz, MD, DrPH, both from Washington University in St. Louis.
This study “has furthered our understanding on sex disparities in cancer, particularly in terms of the contributions of risk factors.”
However, as it included a largely elderly population and omitted comorbidities such as hypertension, hypercholesterolemia, and cardiovascular disease, the study has some “pertinent” limitations, they said.
The contribution of risk factors to sex disparities is “likely by means of complex interactions,” and the editorialists wondered if the statistical modeling used in the study was “over-stringent.” Other aspects that need to be considered include race as well as socioeconomic determinants of health, they suggested.
Nevertheless, they pointed out that sex disparities have been “observed in nearly every aspect of the cancer continuum,” and a “multifaceted approach” is needed to address them.
“Strategically including sex as a biologic variable should be enforced along the whole cancer continuum, from risk prediction and cancer primary prevention, cancer screening, and secondary prevention to cancer treatment and patient management,” Dr. Luo and Dr. Colditz concluded.
Details of the analysis
In their paper, Dr. Jackson and colleagues pointed out that the lifetime probability of developing cancer is “approximately equal” in men and women, at 40% vs. 39%.
However, the burden of cancer at shared anatomic sites is “significantly higher” in men, with the relative risk more than twofold higher than in women.
Some previous studies have pointed to differences in smoking, alcohol use, diet, access to and use of health care, and cancer screening between men and women, to explain the sex disparity, the researchers noted, but few have used individual-level data.
They therefore examined records from the prospective National Institutes of Health–AARP Diet and Health Study. This was launched in 1995 with a baseline questionnaire sent to 3.5 million members of AARP aged 50-71 years and living in six U.S. states. At the time, 617,119 returned the baseline questionnaire (a 17.6% response rate).
The current study focused on 334,905 participants who also completed a follow-up questionnaire between 1996 and 1997, which included more detailed information on diet and other lifestyle factors.
After excluding those who had already had a cancer diagnosis, self-reported poor health, extremely high or low caloric intake, or conflicting gender information, the researchers focused on 294,100 individuals (58% men, 42% women, median age 63.5 years).
After more than a decade of follow-up (mean of 11.5 person-years for men and 12.4 person-years for women), the team found 26,693 incident cancers at 21 shared anatomical cancer sites. Of those, 17,951 were in men and 8,742 in women.
The five most common cancers were nearly the same: the top three were lung, colon, and skin cancer in both men and women, and the fifth most common was kidney cancer in both. No. 4 for men was bladder cancer and for women it was pancreatic cancer.
After adjusting for demographic, lifestyle, and dietary covariates, the researchers found that the cancers with the highest male-to-female hazard ratios were esophageal adenocarcinoma, at 10.80, larynx cancer, at 3.53, gastric cardia cancer, at 3.49, and bladder cancer, at 3.33.
In contrast, men had a reduced risk of thyroid cancer, at a hazard ratio versus women of 0.55, and gallbladder cancer, at a hazard ratio of 0.33.
The team said that, overall, the increased relative risk among men was retained after adjustment for covariates for 11 cancers, but the relationship was no longer significant for many others, including lung, pancreas, small intestine, colon, oral cavity, esophagus-squamous cell carcinoma, and other head and neck cancers.
Cox proportional hazards regression modeling using the Peters-Belson method indicated that sex differences in risk factors explained at least some of the observed differences between men and women for seven cancer sites.
These were lung, colon, rectum, other biliary tract, skin, bladder, and esophageal adenocarcinoma, with 11.2% of the variance explained by risk factor differences for esophageal adenocarcinoma, rising to 49.4% for lung cancer.
There were no significant interactions between cancer rates at any of the anatomic sites and alcohol use, smoking status, body mass index, and age group.
Dr. Jackson told this news organization that sex differences in cancer outcomes “represents a very promising area of research” and the researchers “absolutely want to examine these associations further.”
“The dataset we used consists largely of non-Hispanic White adults. We’d like to see if the same sex bias is present in other ethnic groups, which would provide more evidence for a biological basis for these differences.
“We’d also like to explore the contribution of sex hormones and genetics to cancer incidence in future research,” Dr. Jackson added.
The study was funded by the Intramural Research Program of the National Institutes of Health, National Cancer Institute. Morgan A. Marks, PhD, performed this work as a postdoctoral fellow at the division of cancer epidemiology and genetics, National Cancer Institute. Dr. Marks reports relationships with Merck outside the submitted work.
The editorial was supported in part by a National Cancer Institute Cancer Center Support Grant. Dr. Luo reports grants from the National Institutes of Health outside the submitted work. Dr. Colditz reports grants from the Breast Cancer Research Foundation and the National Cancer Institute outside the submitted work.
No other relevant financial relationships were declared.
A version of this article first appeared on Medscape.com.
Men have a significantly increased risk of developing 11 different cancers, and the risk is three times greater for men for certain cancers, including those of the esophagus, larynx, gastric cardia, and bladder.
But why?
“There are differences in cancer incidence that are not explained by environmental exposures alone,” said lead author Sarah S. Jackson, PhD, of the division of cancer epidemiology and genetics at the National Cancer Institute in Bethesda, Md.
“This suggests that there are intrinsic biological differences between men and women that affect susceptibility to cancer,” she added in a statement.
The study was published online in the journal Cancer.
“Understanding the sex-related biologic mechanisms that lead to the male predominance of cancer at shared anatomic sites could have important implications for etiology and prevention,” the researchers suggested.
In an interview, Dr. Jackson said that the results “do not support changes to existing cancer prevention protocol” to address the disparities in cancer rates between men and women.
“More research is needed before any recommendations can be made,” she told this news organization. “For example, we need more research on the female immune response. If we can discover the mechanisms by which females have an immune advantage, we may be able to develop therapeutics to bolster the immune system to prevent and treat cancer.
“We also should start reporting our findings on cancer incidence, screening, and survival by sex to ensure that we are not missing important sex-specific associations.”
Comprehensive analyses
The researchers “should be applauded” for their “thorough and comprehensive analyses,” said the authors of an accompanying editorial, Jingqin R. Luo, PhD, and Graham A. Colditz, MD, DrPH, both from Washington University in St. Louis.
This study “has furthered our understanding on sex disparities in cancer, particularly in terms of the contributions of risk factors.”
However, as it included a largely elderly population and omitted comorbidities such as hypertension, hypercholesterolemia, and cardiovascular disease, the study has some “pertinent” limitations, they said.
The contribution of risk factors to sex disparities is “likely by means of complex interactions,” and the editorialists wondered if the statistical modeling used in the study was “over-stringent.” Other aspects that need to be considered include race as well as socioeconomic determinants of health, they suggested.
Nevertheless, they pointed out that sex disparities have been “observed in nearly every aspect of the cancer continuum,” and a “multifaceted approach” is needed to address them.
“Strategically including sex as a biologic variable should be enforced along the whole cancer continuum, from risk prediction and cancer primary prevention, cancer screening, and secondary prevention to cancer treatment and patient management,” Dr. Luo and Dr. Colditz concluded.
Details of the analysis
In their paper, Dr. Jackson and colleagues pointed out that the lifetime probability of developing cancer is “approximately equal” in men and women, at 40% vs. 39%.
However, the burden of cancer at shared anatomic sites is “significantly higher” in men, with the relative risk more than twofold higher than in women.
Some previous studies have pointed to differences in smoking, alcohol use, diet, access to and use of health care, and cancer screening between men and women, to explain the sex disparity, the researchers noted, but few have used individual-level data.
They therefore examined records from the prospective National Institutes of Health–AARP Diet and Health Study. This was launched in 1995 with a baseline questionnaire sent to 3.5 million members of AARP aged 50-71 years and living in six U.S. states. At the time, 617,119 returned the baseline questionnaire (a 17.6% response rate).
The current study focused on 334,905 participants who also completed a follow-up questionnaire between 1996 and 1997, which included more detailed information on diet and other lifestyle factors.
After excluding those who had already had a cancer diagnosis, self-reported poor health, extremely high or low caloric intake, or conflicting gender information, the researchers focused on 294,100 individuals (58% men, 42% women, median age 63.5 years).
After more than a decade of follow-up (mean of 11.5 person-years for men and 12.4 person-years for women), the team found 26,693 incident cancers at 21 shared anatomical cancer sites. Of those, 17,951 were in men and 8,742 in women.
The five most common cancers were nearly the same: the top three were lung, colon, and skin cancer in both men and women, and the fifth most common was kidney cancer in both. No. 4 for men was bladder cancer and for women it was pancreatic cancer.
After adjusting for demographic, lifestyle, and dietary covariates, the researchers found that the cancers with the highest male-to-female hazard ratios were esophageal adenocarcinoma, at 10.80, larynx cancer, at 3.53, gastric cardia cancer, at 3.49, and bladder cancer, at 3.33.
In contrast, men had a reduced risk of thyroid cancer, at a hazard ratio versus women of 0.55, and gallbladder cancer, at a hazard ratio of 0.33.
The team said that, overall, the increased relative risk among men was retained after adjustment for covariates for 11 cancers, but the relationship was no longer significant for many others, including lung, pancreas, small intestine, colon, oral cavity, esophagus-squamous cell carcinoma, and other head and neck cancers.
Cox proportional hazards regression modeling using the Peters-Belson method indicated that sex differences in risk factors explained at least some of the observed differences between men and women for seven cancer sites.
These were lung, colon, rectum, other biliary tract, skin, bladder, and esophageal adenocarcinoma, with 11.2% of the variance explained by risk factor differences for esophageal adenocarcinoma, rising to 49.4% for lung cancer.
There were no significant interactions between cancer rates at any of the anatomic sites and alcohol use, smoking status, body mass index, and age group.
Dr. Jackson told this news organization that sex differences in cancer outcomes “represents a very promising area of research” and the researchers “absolutely want to examine these associations further.”
“The dataset we used consists largely of non-Hispanic White adults. We’d like to see if the same sex bias is present in other ethnic groups, which would provide more evidence for a biological basis for these differences.
“We’d also like to explore the contribution of sex hormones and genetics to cancer incidence in future research,” Dr. Jackson added.
The study was funded by the Intramural Research Program of the National Institutes of Health, National Cancer Institute. Morgan A. Marks, PhD, performed this work as a postdoctoral fellow at the division of cancer epidemiology and genetics, National Cancer Institute. Dr. Marks reports relationships with Merck outside the submitted work.
The editorial was supported in part by a National Cancer Institute Cancer Center Support Grant. Dr. Luo reports grants from the National Institutes of Health outside the submitted work. Dr. Colditz reports grants from the Breast Cancer Research Foundation and the National Cancer Institute outside the submitted work.
No other relevant financial relationships were declared.
A version of this article first appeared on Medscape.com.
Men have a significantly increased risk of developing 11 different cancers, and the risk is three times greater for men for certain cancers, including those of the esophagus, larynx, gastric cardia, and bladder.
But why?
“There are differences in cancer incidence that are not explained by environmental exposures alone,” said lead author Sarah S. Jackson, PhD, of the division of cancer epidemiology and genetics at the National Cancer Institute in Bethesda, Md.
“This suggests that there are intrinsic biological differences between men and women that affect susceptibility to cancer,” she added in a statement.
The study was published online in the journal Cancer.
“Understanding the sex-related biologic mechanisms that lead to the male predominance of cancer at shared anatomic sites could have important implications for etiology and prevention,” the researchers suggested.
In an interview, Dr. Jackson said that the results “do not support changes to existing cancer prevention protocol” to address the disparities in cancer rates between men and women.
“More research is needed before any recommendations can be made,” she told this news organization. “For example, we need more research on the female immune response. If we can discover the mechanisms by which females have an immune advantage, we may be able to develop therapeutics to bolster the immune system to prevent and treat cancer.
“We also should start reporting our findings on cancer incidence, screening, and survival by sex to ensure that we are not missing important sex-specific associations.”
Comprehensive analyses
The researchers “should be applauded” for their “thorough and comprehensive analyses,” said the authors of an accompanying editorial, Jingqin R. Luo, PhD, and Graham A. Colditz, MD, DrPH, both from Washington University in St. Louis.
This study “has furthered our understanding on sex disparities in cancer, particularly in terms of the contributions of risk factors.”
However, as it included a largely elderly population and omitted comorbidities such as hypertension, hypercholesterolemia, and cardiovascular disease, the study has some “pertinent” limitations, they said.
The contribution of risk factors to sex disparities is “likely by means of complex interactions,” and the editorialists wondered if the statistical modeling used in the study was “over-stringent.” Other aspects that need to be considered include race as well as socioeconomic determinants of health, they suggested.
Nevertheless, they pointed out that sex disparities have been “observed in nearly every aspect of the cancer continuum,” and a “multifaceted approach” is needed to address them.
“Strategically including sex as a biologic variable should be enforced along the whole cancer continuum, from risk prediction and cancer primary prevention, cancer screening, and secondary prevention to cancer treatment and patient management,” Dr. Luo and Dr. Colditz concluded.
Details of the analysis
In their paper, Dr. Jackson and colleagues pointed out that the lifetime probability of developing cancer is “approximately equal” in men and women, at 40% vs. 39%.
However, the burden of cancer at shared anatomic sites is “significantly higher” in men, with the relative risk more than twofold higher than in women.
Some previous studies have pointed to differences in smoking, alcohol use, diet, access to and use of health care, and cancer screening between men and women, to explain the sex disparity, the researchers noted, but few have used individual-level data.
They therefore examined records from the prospective National Institutes of Health–AARP Diet and Health Study. This was launched in 1995 with a baseline questionnaire sent to 3.5 million members of AARP aged 50-71 years and living in six U.S. states. At the time, 617,119 returned the baseline questionnaire (a 17.6% response rate).
The current study focused on 334,905 participants who also completed a follow-up questionnaire between 1996 and 1997, which included more detailed information on diet and other lifestyle factors.
After excluding those who had already had a cancer diagnosis, self-reported poor health, extremely high or low caloric intake, or conflicting gender information, the researchers focused on 294,100 individuals (58% men, 42% women, median age 63.5 years).
After more than a decade of follow-up (mean of 11.5 person-years for men and 12.4 person-years for women), the team found 26,693 incident cancers at 21 shared anatomical cancer sites. Of those, 17,951 were in men and 8,742 in women.
The five most common cancers were nearly the same: the top three were lung, colon, and skin cancer in both men and women, and the fifth most common was kidney cancer in both. No. 4 for men was bladder cancer and for women it was pancreatic cancer.
After adjusting for demographic, lifestyle, and dietary covariates, the researchers found that the cancers with the highest male-to-female hazard ratios were esophageal adenocarcinoma, at 10.80, larynx cancer, at 3.53, gastric cardia cancer, at 3.49, and bladder cancer, at 3.33.
In contrast, men had a reduced risk of thyroid cancer, at a hazard ratio versus women of 0.55, and gallbladder cancer, at a hazard ratio of 0.33.
The team said that, overall, the increased relative risk among men was retained after adjustment for covariates for 11 cancers, but the relationship was no longer significant for many others, including lung, pancreas, small intestine, colon, oral cavity, esophagus-squamous cell carcinoma, and other head and neck cancers.
Cox proportional hazards regression modeling using the Peters-Belson method indicated that sex differences in risk factors explained at least some of the observed differences between men and women for seven cancer sites.
These were lung, colon, rectum, other biliary tract, skin, bladder, and esophageal adenocarcinoma, with 11.2% of the variance explained by risk factor differences for esophageal adenocarcinoma, rising to 49.4% for lung cancer.
There were no significant interactions between cancer rates at any of the anatomic sites and alcohol use, smoking status, body mass index, and age group.
Dr. Jackson told this news organization that sex differences in cancer outcomes “represents a very promising area of research” and the researchers “absolutely want to examine these associations further.”
“The dataset we used consists largely of non-Hispanic White adults. We’d like to see if the same sex bias is present in other ethnic groups, which would provide more evidence for a biological basis for these differences.
“We’d also like to explore the contribution of sex hormones and genetics to cancer incidence in future research,” Dr. Jackson added.
The study was funded by the Intramural Research Program of the National Institutes of Health, National Cancer Institute. Morgan A. Marks, PhD, performed this work as a postdoctoral fellow at the division of cancer epidemiology and genetics, National Cancer Institute. Dr. Marks reports relationships with Merck outside the submitted work.
The editorial was supported in part by a National Cancer Institute Cancer Center Support Grant. Dr. Luo reports grants from the National Institutes of Health outside the submitted work. Dr. Colditz reports grants from the Breast Cancer Research Foundation and the National Cancer Institute outside the submitted work.
No other relevant financial relationships were declared.
A version of this article first appeared on Medscape.com.
Mindfulness ‘changes the biology’ of pain
In a randomized trial, more than 100 healthy individuals were assigned to an 8-week mindfulness-based stress reduction (MBSR) program, a health improvement program (HEP) of the same length, or a waiting list.
Scanning participants’ brains during a heat-based stimulus pain task showed those who completed the MBSR had a reduction in a brain signature linked to the sensory intensity of pain.
“Our finding supports the idea that for new practitioners, mindfulness training directly affects how sensory signals from the body are converted into a brain response,” lead investigator Joseph Wielgosz, PhD, of the Center for Healthy Minds, University of Wisconsin–Madison, said in a release.
Further analysis in long-term meditation practitioners showed the total time spent on intensive retreats was associated with neural changes associated with the perceived stress of pain.
“Just like an experienced athlete plays a sport differently than a first-timer, experienced mindfulness practitioners seem to use their mental ‘muscles’ differently in response to pain than first-time meditators,” Dr. Wielgosz noted.
The findings were published online in the American Journal of Psychiatry.
A complex condition
Dr. Wielgosz told this news organization that pain is “complex,” with multiple stages and several phases between the time signals are sent from pain receptors and the experience of pain.
“The way that mindfulness affects pain processing has more to do with the way the brain interprets pain signals.”
The investigators note that understanding the neurocognitive mechanisms underlying the efficacy of nonpharmacologic pain interventions is a “high-priority objective for improving pain treatment.”
Evidence from brief laboratory interventions and cross-sectional studies suggests that mindfulness training is associated with alterations in both sensory processing and cognitive-emotional regulatory networks, the investigators note.
“However, no such study has yet been conducted on a standardized, full-length, and widely used clinical intervention, such as MBSR,” they add.
Thermal pain task
The randomized, active-control trial included 115 healthy, meditation-naive individuals (61.7% women; average age, 48.3 years). Just over half (58%) had a graduate degree and their mean score on the Hollingshead index was 58.3, indicting a higher socioeconomic status.
All were randomly assigned to an 8-week MBSR course, an 8-week HEP course as an active control group, or a waiting-list control group with no intervention.
The MBSR involved instruction and practice in continuous focused attention on the breath, bodily sensations, and mental content while in seated postures, walking, and doing yoga.
The HEP matched the MBSR in terms of its length, structure, and nonspecific therapeutic elements, which included a supportive group atmosphere, expert instruction, and positive expectancy for benefit.
To examine the interventions’ effect on the pain experience, participants underwent a pain task in which they had 20 thermal stimuli applied to the inside of the left wrist for 12 seconds, including 8 seconds at peak temperature.
The stimuli were separated by a distractor task and intervals for cued anticipation, recovery, and subjective ratings of intensity and unpleasantness on a scale of 0-20.
During the task, participants underwent MRI to assess the neurologic pain signature (NPS) and the stimulus intensity independent pain signature-1 (SIIPS-1) within the brain.
The NPS is activated by various types of pain stimuli, while responding minimally or not at all to “emotionally evocative stimuli” relating to pain or to placebo treatment, the researchers note.
In contrast, the SIIPS-1 is activated in response to aspects of pain unrelated to the stimulus itself. It incorporates a “broader range of cognitive and emotional modulatory circuits,” including those related to expectancy and cognitive processes to modulate the pain experience.
Neural signatures
Results showed that in all groups, age was significantly negatively associated with both NPS (P = .001) and SIIPS-1 response (P < .001), although not subjective pain reports, and was subsequently included in all analyses of neural signatures.
Persons in the MBSR group had a significant decrease in the NPS, compared with those in the HEP group (P = .05), and from pre- to postintervention assessments (P = .023).
Those in the MBSR group also had “marginal” decreases in the NPS vs. the waiting list group (P = .096), and in the SIIPS-1 relative to both the HEP (P = .089) and waiting list groups (P = .087).
In subjective pain ratings, the MBSR group showed a marginal decrease, compared with the waiting list group (P = .078), and from the pre- to postintervention assessments (P = .028).
The HEP group also had marginal decreases in pain unpleasantness vs. the waiting list group (P = .043), and from the pre- to postintervention assessments for pain intensity (P = .046) and unpleasantness (P = .007).
The researchers also assessed 30 long-term meditators who had undertaken at least 3 years of formal experience with meditation, including participating in multiple intensive retreats and ongoing daily practice, and compared them with meditation-naive individuals.
Long-term meditators reported significantly less pain intensity and unpleasantness than those who had not undergone the training (P < .001).
In addition, a higher number of practice hours during a retreat was linked to a greater reduction in pain ratings. This association remained even after adjustment for gender and respiration rate.
However, the number of daily practice hours was not significantly associated with pain ratings among long-term meditators.
Although there were no average differences in neural signature responses between long-term meditators and individuals who were naive to the technique, there was an inverse relationship between hours on retreat and SIIPS-1 response (P = .027).
‘We’re seeing the biology change’
Commenting for this news organization, Fadel Zeidan, PhD, associate professor of anesthesiology, University of California, San Diego, said that in attenuating the experience of pain, mindfulness engages “very novel” mechanisms.
However, the “most remarkable thing about this study” is that the pain effect occurred when the participants were not meditating, “which gives rise to the notion that mental training is just like physical training,” said Dr. Zeidan, who was not involved with the research.
He noted that the notion was not appreciated previously, “because we weren’t able to see the changes,” as they were based on self-report alone.
However, combining those reports with brain imaging and other objective methods means that “we’re actually seeing the biology change,” Dr. Zeidan said.
He added that mindfulness is different from other techniques for modulating the pain experience, because it is self-facilitated.
“People can learn this technique, ideally, for free online. They can learn the recipe, and it’s one of the only techniques out there that can be used immediately to assuage one’s own pain,” he said.
“There’s nothing else out there on this planet that could immediately reduce one’s own pain. You have to wait 45 minutes for Tylenol, distraction can only work for so long, and you can’t really placebo yourself,” Dr. Zeidan added.
The study was funded by a National Center for Complementary and Alternative Medicine grant, National Institute of Mental Health grants, a Fetzer Institute grant, and a John Templeton Foundation grant, as well as a core grant to the Waisman Center from the National Institute of Child Health and Human Development to Albee Messing. Dr. Wielgosz and Dr. Zeidan have reported no relevant financial relationships. Disclosures for the coinvestigators are listed in the original article.
A version of this article first appeared on Medscape.com.
In a randomized trial, more than 100 healthy individuals were assigned to an 8-week mindfulness-based stress reduction (MBSR) program, a health improvement program (HEP) of the same length, or a waiting list.
Scanning participants’ brains during a heat-based stimulus pain task showed those who completed the MBSR had a reduction in a brain signature linked to the sensory intensity of pain.
“Our finding supports the idea that for new practitioners, mindfulness training directly affects how sensory signals from the body are converted into a brain response,” lead investigator Joseph Wielgosz, PhD, of the Center for Healthy Minds, University of Wisconsin–Madison, said in a release.
Further analysis in long-term meditation practitioners showed the total time spent on intensive retreats was associated with neural changes associated with the perceived stress of pain.
“Just like an experienced athlete plays a sport differently than a first-timer, experienced mindfulness practitioners seem to use their mental ‘muscles’ differently in response to pain than first-time meditators,” Dr. Wielgosz noted.
The findings were published online in the American Journal of Psychiatry.
A complex condition
Dr. Wielgosz told this news organization that pain is “complex,” with multiple stages and several phases between the time signals are sent from pain receptors and the experience of pain.
“The way that mindfulness affects pain processing has more to do with the way the brain interprets pain signals.”
The investigators note that understanding the neurocognitive mechanisms underlying the efficacy of nonpharmacologic pain interventions is a “high-priority objective for improving pain treatment.”
Evidence from brief laboratory interventions and cross-sectional studies suggests that mindfulness training is associated with alterations in both sensory processing and cognitive-emotional regulatory networks, the investigators note.
“However, no such study has yet been conducted on a standardized, full-length, and widely used clinical intervention, such as MBSR,” they add.
Thermal pain task
The randomized, active-control trial included 115 healthy, meditation-naive individuals (61.7% women; average age, 48.3 years). Just over half (58%) had a graduate degree and their mean score on the Hollingshead index was 58.3, indicting a higher socioeconomic status.
All were randomly assigned to an 8-week MBSR course, an 8-week HEP course as an active control group, or a waiting-list control group with no intervention.
The MBSR involved instruction and practice in continuous focused attention on the breath, bodily sensations, and mental content while in seated postures, walking, and doing yoga.
The HEP matched the MBSR in terms of its length, structure, and nonspecific therapeutic elements, which included a supportive group atmosphere, expert instruction, and positive expectancy for benefit.
To examine the interventions’ effect on the pain experience, participants underwent a pain task in which they had 20 thermal stimuli applied to the inside of the left wrist for 12 seconds, including 8 seconds at peak temperature.
The stimuli were separated by a distractor task and intervals for cued anticipation, recovery, and subjective ratings of intensity and unpleasantness on a scale of 0-20.
During the task, participants underwent MRI to assess the neurologic pain signature (NPS) and the stimulus intensity independent pain signature-1 (SIIPS-1) within the brain.
The NPS is activated by various types of pain stimuli, while responding minimally or not at all to “emotionally evocative stimuli” relating to pain or to placebo treatment, the researchers note.
In contrast, the SIIPS-1 is activated in response to aspects of pain unrelated to the stimulus itself. It incorporates a “broader range of cognitive and emotional modulatory circuits,” including those related to expectancy and cognitive processes to modulate the pain experience.
Neural signatures
Results showed that in all groups, age was significantly negatively associated with both NPS (P = .001) and SIIPS-1 response (P < .001), although not subjective pain reports, and was subsequently included in all analyses of neural signatures.
Persons in the MBSR group had a significant decrease in the NPS, compared with those in the HEP group (P = .05), and from pre- to postintervention assessments (P = .023).
Those in the MBSR group also had “marginal” decreases in the NPS vs. the waiting list group (P = .096), and in the SIIPS-1 relative to both the HEP (P = .089) and waiting list groups (P = .087).
In subjective pain ratings, the MBSR group showed a marginal decrease, compared with the waiting list group (P = .078), and from the pre- to postintervention assessments (P = .028).
The HEP group also had marginal decreases in pain unpleasantness vs. the waiting list group (P = .043), and from the pre- to postintervention assessments for pain intensity (P = .046) and unpleasantness (P = .007).
The researchers also assessed 30 long-term meditators who had undertaken at least 3 years of formal experience with meditation, including participating in multiple intensive retreats and ongoing daily practice, and compared them with meditation-naive individuals.
Long-term meditators reported significantly less pain intensity and unpleasantness than those who had not undergone the training (P < .001).
In addition, a higher number of practice hours during a retreat was linked to a greater reduction in pain ratings. This association remained even after adjustment for gender and respiration rate.
However, the number of daily practice hours was not significantly associated with pain ratings among long-term meditators.
Although there were no average differences in neural signature responses between long-term meditators and individuals who were naive to the technique, there was an inverse relationship between hours on retreat and SIIPS-1 response (P = .027).
‘We’re seeing the biology change’
Commenting for this news organization, Fadel Zeidan, PhD, associate professor of anesthesiology, University of California, San Diego, said that in attenuating the experience of pain, mindfulness engages “very novel” mechanisms.
However, the “most remarkable thing about this study” is that the pain effect occurred when the participants were not meditating, “which gives rise to the notion that mental training is just like physical training,” said Dr. Zeidan, who was not involved with the research.
He noted that the notion was not appreciated previously, “because we weren’t able to see the changes,” as they were based on self-report alone.
However, combining those reports with brain imaging and other objective methods means that “we’re actually seeing the biology change,” Dr. Zeidan said.
He added that mindfulness is different from other techniques for modulating the pain experience, because it is self-facilitated.
“People can learn this technique, ideally, for free online. They can learn the recipe, and it’s one of the only techniques out there that can be used immediately to assuage one’s own pain,” he said.
“There’s nothing else out there on this planet that could immediately reduce one’s own pain. You have to wait 45 minutes for Tylenol, distraction can only work for so long, and you can’t really placebo yourself,” Dr. Zeidan added.
The study was funded by a National Center for Complementary and Alternative Medicine grant, National Institute of Mental Health grants, a Fetzer Institute grant, and a John Templeton Foundation grant, as well as a core grant to the Waisman Center from the National Institute of Child Health and Human Development to Albee Messing. Dr. Wielgosz and Dr. Zeidan have reported no relevant financial relationships. Disclosures for the coinvestigators are listed in the original article.
A version of this article first appeared on Medscape.com.
In a randomized trial, more than 100 healthy individuals were assigned to an 8-week mindfulness-based stress reduction (MBSR) program, a health improvement program (HEP) of the same length, or a waiting list.
Scanning participants’ brains during a heat-based stimulus pain task showed those who completed the MBSR had a reduction in a brain signature linked to the sensory intensity of pain.
“Our finding supports the idea that for new practitioners, mindfulness training directly affects how sensory signals from the body are converted into a brain response,” lead investigator Joseph Wielgosz, PhD, of the Center for Healthy Minds, University of Wisconsin–Madison, said in a release.
Further analysis in long-term meditation practitioners showed the total time spent on intensive retreats was associated with neural changes associated with the perceived stress of pain.
“Just like an experienced athlete plays a sport differently than a first-timer, experienced mindfulness practitioners seem to use their mental ‘muscles’ differently in response to pain than first-time meditators,” Dr. Wielgosz noted.
The findings were published online in the American Journal of Psychiatry.
A complex condition
Dr. Wielgosz told this news organization that pain is “complex,” with multiple stages and several phases between the time signals are sent from pain receptors and the experience of pain.
“The way that mindfulness affects pain processing has more to do with the way the brain interprets pain signals.”
The investigators note that understanding the neurocognitive mechanisms underlying the efficacy of nonpharmacologic pain interventions is a “high-priority objective for improving pain treatment.”
Evidence from brief laboratory interventions and cross-sectional studies suggests that mindfulness training is associated with alterations in both sensory processing and cognitive-emotional regulatory networks, the investigators note.
“However, no such study has yet been conducted on a standardized, full-length, and widely used clinical intervention, such as MBSR,” they add.
Thermal pain task
The randomized, active-control trial included 115 healthy, meditation-naive individuals (61.7% women; average age, 48.3 years). Just over half (58%) had a graduate degree and their mean score on the Hollingshead index was 58.3, indicting a higher socioeconomic status.
All were randomly assigned to an 8-week MBSR course, an 8-week HEP course as an active control group, or a waiting-list control group with no intervention.
The MBSR involved instruction and practice in continuous focused attention on the breath, bodily sensations, and mental content while in seated postures, walking, and doing yoga.
The HEP matched the MBSR in terms of its length, structure, and nonspecific therapeutic elements, which included a supportive group atmosphere, expert instruction, and positive expectancy for benefit.
To examine the interventions’ effect on the pain experience, participants underwent a pain task in which they had 20 thermal stimuli applied to the inside of the left wrist for 12 seconds, including 8 seconds at peak temperature.
The stimuli were separated by a distractor task and intervals for cued anticipation, recovery, and subjective ratings of intensity and unpleasantness on a scale of 0-20.
During the task, participants underwent MRI to assess the neurologic pain signature (NPS) and the stimulus intensity independent pain signature-1 (SIIPS-1) within the brain.
The NPS is activated by various types of pain stimuli, while responding minimally or not at all to “emotionally evocative stimuli” relating to pain or to placebo treatment, the researchers note.
In contrast, the SIIPS-1 is activated in response to aspects of pain unrelated to the stimulus itself. It incorporates a “broader range of cognitive and emotional modulatory circuits,” including those related to expectancy and cognitive processes to modulate the pain experience.
Neural signatures
Results showed that in all groups, age was significantly negatively associated with both NPS (P = .001) and SIIPS-1 response (P < .001), although not subjective pain reports, and was subsequently included in all analyses of neural signatures.
Persons in the MBSR group had a significant decrease in the NPS, compared with those in the HEP group (P = .05), and from pre- to postintervention assessments (P = .023).
Those in the MBSR group also had “marginal” decreases in the NPS vs. the waiting list group (P = .096), and in the SIIPS-1 relative to both the HEP (P = .089) and waiting list groups (P = .087).
In subjective pain ratings, the MBSR group showed a marginal decrease, compared with the waiting list group (P = .078), and from the pre- to postintervention assessments (P = .028).
The HEP group also had marginal decreases in pain unpleasantness vs. the waiting list group (P = .043), and from the pre- to postintervention assessments for pain intensity (P = .046) and unpleasantness (P = .007).
The researchers also assessed 30 long-term meditators who had undertaken at least 3 years of formal experience with meditation, including participating in multiple intensive retreats and ongoing daily practice, and compared them with meditation-naive individuals.
Long-term meditators reported significantly less pain intensity and unpleasantness than those who had not undergone the training (P < .001).
In addition, a higher number of practice hours during a retreat was linked to a greater reduction in pain ratings. This association remained even after adjustment for gender and respiration rate.
However, the number of daily practice hours was not significantly associated with pain ratings among long-term meditators.
Although there were no average differences in neural signature responses between long-term meditators and individuals who were naive to the technique, there was an inverse relationship between hours on retreat and SIIPS-1 response (P = .027).
‘We’re seeing the biology change’
Commenting for this news organization, Fadel Zeidan, PhD, associate professor of anesthesiology, University of California, San Diego, said that in attenuating the experience of pain, mindfulness engages “very novel” mechanisms.
However, the “most remarkable thing about this study” is that the pain effect occurred when the participants were not meditating, “which gives rise to the notion that mental training is just like physical training,” said Dr. Zeidan, who was not involved with the research.
He noted that the notion was not appreciated previously, “because we weren’t able to see the changes,” as they were based on self-report alone.
However, combining those reports with brain imaging and other objective methods means that “we’re actually seeing the biology change,” Dr. Zeidan said.
He added that mindfulness is different from other techniques for modulating the pain experience, because it is self-facilitated.
“People can learn this technique, ideally, for free online. They can learn the recipe, and it’s one of the only techniques out there that can be used immediately to assuage one’s own pain,” he said.
“There’s nothing else out there on this planet that could immediately reduce one’s own pain. You have to wait 45 minutes for Tylenol, distraction can only work for so long, and you can’t really placebo yourself,” Dr. Zeidan added.
The study was funded by a National Center for Complementary and Alternative Medicine grant, National Institute of Mental Health grants, a Fetzer Institute grant, and a John Templeton Foundation grant, as well as a core grant to the Waisman Center from the National Institute of Child Health and Human Development to Albee Messing. Dr. Wielgosz and Dr. Zeidan have reported no relevant financial relationships. Disclosures for the coinvestigators are listed in the original article.
A version of this article first appeared on Medscape.com.
FROM AMERICAN JOURNAL OF PSYCHIATRY
Poor sleep raises risk for fatty liver disease
Sleep behaviors, both individually and combined, are associated with an increased risk of developing metabolic dysfunction–associated fatty liver disease (MAFLD), according to a Chinese analysis that suggests the effect may be independent of obesity.
Yan Liu, PhD, from the School of Public Health at Sun Yat-sen University in Guangzhou, China, and colleagues studied data on over 5,000 individuals who self-reported sleep behaviors and underwent liver ultrasound.
, increasing the risk by 37%, 59%, and 17%, respectively, whereas people with both poor nighttime sleep and prolonged daytime napping had the “highest risk for developing fatty liver disease,” said Dr. Liu in a press release.
In contrast, having any of six healthy sleep behaviors decreased the risk by 16% each, and even a “moderate improvement in sleep quality was related to a 29% reduction in the risk for fatty liver disease,” he added.
The research, published online in the Journal of Clinical Endocrinology & Metabolism, also indicated that obesity accounted for only one fifth of the effect of sleep quality on MAFLD risk.
Rise in unhealthy lifestyles leads to increase in MALFD
The authors write that MAFLD is the “leading chronic liver disease worldwide,” affecting around a quarter of the adult population, and may lead to end-stage liver diseases and extrahepatic complications, thus “posing a major health and economic burden.”
Moreover, the disease prevalence is “soaring at an unanticipated rate,” increasing from 18% to 29% in China over the past decade, because of a “rapid rise in unhealthy lifestyles,” the authors note.
Sleep disturbance is increasingly prevalent, “and an emerging contributor to multiple metabolic disorders,” with insomnia and habitual snoring, for example, positively correlated with hypertension, impaired glucose metabolism, and dyslipidemia, report the authors.
However, whether sleep quality, which includes “several metabolic-related sleep behaviors,” constitutes an independent risk for MAFLD “over and above” the effect of obesity remains unclear.
To investigate further, the researchers examined data from the baseline survey of the community-based, prospective South China Cohort study, which was conducted in four regions of Southern China and involved 5,430 individuals aged 30-79 years.
Between March 2018 and October 2019, the participants self-reported sleep behaviors on the Pittsburgh Sleep Quality Index questionnaire and underwent ultrasound examination of the liver.
MAFLD was diagnosed in those with hepatic steatosis and one of the following:
- Overweight/obesity, defined by this study as a body mass index greater than or equal to 23 kg/m2.
- Presence of diabetes.
- Evidence of metabolic dysregulation.
After excluding patients with insufficient data, and those with a history of liver cirrhosis, hepatectomy, or liver cancer, among others, the team included 5,011 individuals with an average age of 64 years and a mean body mass index of 24.31 kg/m2. Forty percent were male.
Obesity was present in 13% of participants, whereas 15% had diabetes, 58% hypertension, and 35% metabolic syndrome.
MAFLD was diagnosed in 28% of the study population. They were older, more likely to be female with a higher education, and had a higher prevalence of preexisting metabolic disorders and worse metabolic profiles, than those without the disease.
Turning to the associations between sleep and the risk of MAFLD, the researchers say that “in contrast to previous reports, neither shorter nor longer sleep duration was found to be associated with the risk for MAFLD.”
However, after adjusting for demographics, lifestyles, medication, and preexisting metabolic comorbidities including hypertension, diabetes, and obesity, they found that the risk of MAFLD was significantly associated with late bedtime (defined as after 10 p.m.), at an odds ratio of 1.37 (P < .05).
MAFLD was also linked to snoring, at an odds ratio of 1.59, and to daytime napping for longer than 30 minutes, at an odds ratio of 1.17 (P < .05 for both).
When the team compared low-risk and high-risk sleep factors, they found that participants who had an early bedtime, slept 7-8 hours per night, never or rarely had insomnia or snoring, had infrequent daytime sleepiness, and daytime napping of half-hour or less had an odds ratio for MAFLD vs. other participants of 0.64 (P < .05).
Combining those factors into a healthy sleep score, the team found that each additional increase of healthy sleep score was associated with a fully adjusted odds ratio for MAFLD of 0.84 (P < .05).
In contrast, individuals with poor nocturnal sleep patterns and prolonged daytime napping had a higher risk for developing MAFLD, compared with those with a healthy nocturnal sleep pattern and daytime napping of half-hour or less, at an odds ratio of 2.38 (P < .05).
Further analysis indicated that individuals with a sedentary lifestyle and central obesity had a higher risk of MAFLD, but that the presence of obesity accounted for only 20.8% of the total effect of sleep quality on the risk of MAFLD.
“Taken together, our results suggests that obesity only partially mediates the effect of overall sleep quality on MAFLD,” the authors write.
“Given that large proportions of subjects suffering from poor sleep quality are underdiagnosed and undertreated, our study calls for more research into this field and strategies to improve sleep quality,” Dr. Liu said.
The study was supported by the “National Key R&D Program” of China, the Fundamental Research Funds for the Central Universities (Sun Yat-sen University), Natural Science Foundation of Guangdong Province, the Key Project of Medicine Discipline of Guangzhou, and Basic Research Project of Key Laboratory of Guangzhou.
The authors report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Sleep behaviors, both individually and combined, are associated with an increased risk of developing metabolic dysfunction–associated fatty liver disease (MAFLD), according to a Chinese analysis that suggests the effect may be independent of obesity.
Yan Liu, PhD, from the School of Public Health at Sun Yat-sen University in Guangzhou, China, and colleagues studied data on over 5,000 individuals who self-reported sleep behaviors and underwent liver ultrasound.
, increasing the risk by 37%, 59%, and 17%, respectively, whereas people with both poor nighttime sleep and prolonged daytime napping had the “highest risk for developing fatty liver disease,” said Dr. Liu in a press release.
In contrast, having any of six healthy sleep behaviors decreased the risk by 16% each, and even a “moderate improvement in sleep quality was related to a 29% reduction in the risk for fatty liver disease,” he added.
The research, published online in the Journal of Clinical Endocrinology & Metabolism, also indicated that obesity accounted for only one fifth of the effect of sleep quality on MAFLD risk.
Rise in unhealthy lifestyles leads to increase in MALFD
The authors write that MAFLD is the “leading chronic liver disease worldwide,” affecting around a quarter of the adult population, and may lead to end-stage liver diseases and extrahepatic complications, thus “posing a major health and economic burden.”
Moreover, the disease prevalence is “soaring at an unanticipated rate,” increasing from 18% to 29% in China over the past decade, because of a “rapid rise in unhealthy lifestyles,” the authors note.
Sleep disturbance is increasingly prevalent, “and an emerging contributor to multiple metabolic disorders,” with insomnia and habitual snoring, for example, positively correlated with hypertension, impaired glucose metabolism, and dyslipidemia, report the authors.
However, whether sleep quality, which includes “several metabolic-related sleep behaviors,” constitutes an independent risk for MAFLD “over and above” the effect of obesity remains unclear.
To investigate further, the researchers examined data from the baseline survey of the community-based, prospective South China Cohort study, which was conducted in four regions of Southern China and involved 5,430 individuals aged 30-79 years.
Between March 2018 and October 2019, the participants self-reported sleep behaviors on the Pittsburgh Sleep Quality Index questionnaire and underwent ultrasound examination of the liver.
MAFLD was diagnosed in those with hepatic steatosis and one of the following:
- Overweight/obesity, defined by this study as a body mass index greater than or equal to 23 kg/m2.
- Presence of diabetes.
- Evidence of metabolic dysregulation.
After excluding patients with insufficient data, and those with a history of liver cirrhosis, hepatectomy, or liver cancer, among others, the team included 5,011 individuals with an average age of 64 years and a mean body mass index of 24.31 kg/m2. Forty percent were male.
Obesity was present in 13% of participants, whereas 15% had diabetes, 58% hypertension, and 35% metabolic syndrome.
MAFLD was diagnosed in 28% of the study population. They were older, more likely to be female with a higher education, and had a higher prevalence of preexisting metabolic disorders and worse metabolic profiles, than those without the disease.
Turning to the associations between sleep and the risk of MAFLD, the researchers say that “in contrast to previous reports, neither shorter nor longer sleep duration was found to be associated with the risk for MAFLD.”
However, after adjusting for demographics, lifestyles, medication, and preexisting metabolic comorbidities including hypertension, diabetes, and obesity, they found that the risk of MAFLD was significantly associated with late bedtime (defined as after 10 p.m.), at an odds ratio of 1.37 (P < .05).
MAFLD was also linked to snoring, at an odds ratio of 1.59, and to daytime napping for longer than 30 minutes, at an odds ratio of 1.17 (P < .05 for both).
When the team compared low-risk and high-risk sleep factors, they found that participants who had an early bedtime, slept 7-8 hours per night, never or rarely had insomnia or snoring, had infrequent daytime sleepiness, and daytime napping of half-hour or less had an odds ratio for MAFLD vs. other participants of 0.64 (P < .05).
Combining those factors into a healthy sleep score, the team found that each additional increase of healthy sleep score was associated with a fully adjusted odds ratio for MAFLD of 0.84 (P < .05).
In contrast, individuals with poor nocturnal sleep patterns and prolonged daytime napping had a higher risk for developing MAFLD, compared with those with a healthy nocturnal sleep pattern and daytime napping of half-hour or less, at an odds ratio of 2.38 (P < .05).
Further analysis indicated that individuals with a sedentary lifestyle and central obesity had a higher risk of MAFLD, but that the presence of obesity accounted for only 20.8% of the total effect of sleep quality on the risk of MAFLD.
“Taken together, our results suggests that obesity only partially mediates the effect of overall sleep quality on MAFLD,” the authors write.
“Given that large proportions of subjects suffering from poor sleep quality are underdiagnosed and undertreated, our study calls for more research into this field and strategies to improve sleep quality,” Dr. Liu said.
The study was supported by the “National Key R&D Program” of China, the Fundamental Research Funds for the Central Universities (Sun Yat-sen University), Natural Science Foundation of Guangdong Province, the Key Project of Medicine Discipline of Guangzhou, and Basic Research Project of Key Laboratory of Guangzhou.
The authors report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Sleep behaviors, both individually and combined, are associated with an increased risk of developing metabolic dysfunction–associated fatty liver disease (MAFLD), according to a Chinese analysis that suggests the effect may be independent of obesity.
Yan Liu, PhD, from the School of Public Health at Sun Yat-sen University in Guangzhou, China, and colleagues studied data on over 5,000 individuals who self-reported sleep behaviors and underwent liver ultrasound.
, increasing the risk by 37%, 59%, and 17%, respectively, whereas people with both poor nighttime sleep and prolonged daytime napping had the “highest risk for developing fatty liver disease,” said Dr. Liu in a press release.
In contrast, having any of six healthy sleep behaviors decreased the risk by 16% each, and even a “moderate improvement in sleep quality was related to a 29% reduction in the risk for fatty liver disease,” he added.
The research, published online in the Journal of Clinical Endocrinology & Metabolism, also indicated that obesity accounted for only one fifth of the effect of sleep quality on MAFLD risk.
Rise in unhealthy lifestyles leads to increase in MALFD
The authors write that MAFLD is the “leading chronic liver disease worldwide,” affecting around a quarter of the adult population, and may lead to end-stage liver diseases and extrahepatic complications, thus “posing a major health and economic burden.”
Moreover, the disease prevalence is “soaring at an unanticipated rate,” increasing from 18% to 29% in China over the past decade, because of a “rapid rise in unhealthy lifestyles,” the authors note.
Sleep disturbance is increasingly prevalent, “and an emerging contributor to multiple metabolic disorders,” with insomnia and habitual snoring, for example, positively correlated with hypertension, impaired glucose metabolism, and dyslipidemia, report the authors.
However, whether sleep quality, which includes “several metabolic-related sleep behaviors,” constitutes an independent risk for MAFLD “over and above” the effect of obesity remains unclear.
To investigate further, the researchers examined data from the baseline survey of the community-based, prospective South China Cohort study, which was conducted in four regions of Southern China and involved 5,430 individuals aged 30-79 years.
Between March 2018 and October 2019, the participants self-reported sleep behaviors on the Pittsburgh Sleep Quality Index questionnaire and underwent ultrasound examination of the liver.
MAFLD was diagnosed in those with hepatic steatosis and one of the following:
- Overweight/obesity, defined by this study as a body mass index greater than or equal to 23 kg/m2.
- Presence of diabetes.
- Evidence of metabolic dysregulation.
After excluding patients with insufficient data, and those with a history of liver cirrhosis, hepatectomy, or liver cancer, among others, the team included 5,011 individuals with an average age of 64 years and a mean body mass index of 24.31 kg/m2. Forty percent were male.
Obesity was present in 13% of participants, whereas 15% had diabetes, 58% hypertension, and 35% metabolic syndrome.
MAFLD was diagnosed in 28% of the study population. They were older, more likely to be female with a higher education, and had a higher prevalence of preexisting metabolic disorders and worse metabolic profiles, than those without the disease.
Turning to the associations between sleep and the risk of MAFLD, the researchers say that “in contrast to previous reports, neither shorter nor longer sleep duration was found to be associated with the risk for MAFLD.”
However, after adjusting for demographics, lifestyles, medication, and preexisting metabolic comorbidities including hypertension, diabetes, and obesity, they found that the risk of MAFLD was significantly associated with late bedtime (defined as after 10 p.m.), at an odds ratio of 1.37 (P < .05).
MAFLD was also linked to snoring, at an odds ratio of 1.59, and to daytime napping for longer than 30 minutes, at an odds ratio of 1.17 (P < .05 for both).
When the team compared low-risk and high-risk sleep factors, they found that participants who had an early bedtime, slept 7-8 hours per night, never or rarely had insomnia or snoring, had infrequent daytime sleepiness, and daytime napping of half-hour or less had an odds ratio for MAFLD vs. other participants of 0.64 (P < .05).
Combining those factors into a healthy sleep score, the team found that each additional increase of healthy sleep score was associated with a fully adjusted odds ratio for MAFLD of 0.84 (P < .05).
In contrast, individuals with poor nocturnal sleep patterns and prolonged daytime napping had a higher risk for developing MAFLD, compared with those with a healthy nocturnal sleep pattern and daytime napping of half-hour or less, at an odds ratio of 2.38 (P < .05).
Further analysis indicated that individuals with a sedentary lifestyle and central obesity had a higher risk of MAFLD, but that the presence of obesity accounted for only 20.8% of the total effect of sleep quality on the risk of MAFLD.
“Taken together, our results suggests that obesity only partially mediates the effect of overall sleep quality on MAFLD,” the authors write.
“Given that large proportions of subjects suffering from poor sleep quality are underdiagnosed and undertreated, our study calls for more research into this field and strategies to improve sleep quality,” Dr. Liu said.
The study was supported by the “National Key R&D Program” of China, the Fundamental Research Funds for the Central Universities (Sun Yat-sen University), Natural Science Foundation of Guangdong Province, the Key Project of Medicine Discipline of Guangzhou, and Basic Research Project of Key Laboratory of Guangzhou.
The authors report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
Rethinking histology as treatment target in ulcerative colitis
For patients who experience endoscopic remission of ulcerative colitis (UC), signs of active disease on histology did not affect their risk of clinical relapse, according to a large prospective study that reinforces a low endoscopy score as the treatment target.
In the study of more than 250 patients in endoscopic remission from UC, 19% experienced a clinical relapse within 1 year. The researchers found that a lower baseline endoscopy score was linked to a lower risk of relapse.
While histologic activity, as reflected in the Geboes Score, was not associated with clinical relapse, the presence of basal plasmacytosis independently doubled the risk of relapse.
“Our findings do not support the use of histology as a target for treatment in patients with ulcerative colitis who already achieved clinical and endoscopic remission,” say Talat Bessissow, MD, McGill University Health Center, Montreal, and colleagues.
They add that the results “support the use of the Mayo endoscopic subscore of zero as the optimal target for endoscopic remission.”
Further prospective data are needed to “define the role of histology activity and basal plasmacytosis in the management of ulcerative colitis,” the authors write.
The study was published online in The American Journal of Gastroenterology.
Uncertain role of histology
Dr. Bessissow told this news organization that “some studies have shown that histologic healing is associated with better long-term outcomes and less relapse, but this topic remains controversial because other studies have shown the opposite.”
“Our study does not support histology as a treatment target,” he continued, adding that therapy should not be changed solely on the basis of histology.
Dr. Bessissow clarified that although histology was not associated with less relapse over 1 year of follow-up, the role of histology on other, longer-term outcomes, such as surgery and colorectal cancer, still needs to be studied.
The natural history of UC is characterized by frequent relapse, the authors write, but “treating symptoms alone is not sufficient to prevent long-term complications.”
This led to a shift toward using endoscopic healing as a therapeutic goal, a move that was aided by the advent of novel medical therapies, including biologic agents. Crucially, endoscopic healing is associated with improved long-term outcomes, as well as improved quality of life.
The authors continue, however, that a “significant proportion” of patients experience relapse despite achieving endoscopic healing, which “could be explained in part by the fact that up to 40% of patients in endoscopic healing will have ongoing active histologic disease.”
However, in studies in which histologic activity was an endpoint, results have conflicted, and questions remain as to which parameters to include when assessing histologic activity.
Measuring the predictive values of endoscopy and histology
To investigate further, the researchers conducted a prospective observational study of consecutive adult patients with confirmed UC who presented to an endoscopy unit for colonoscopy for disease assessment or surveillance.
To qualify for the study, the patients’ conditions had to have been in clinical remission for at least 3 months prior to the colonoscopy. They were excluded if they had undergone prior surgical resection, had experienced disease remission for a period of over 10 years, or had used oral or rectal steroids within 90 days, among other criteria.
During an initial colonoscopy, two biopsies were performed, with specimens taken from the rectosigmoid and, when possible, from the right and left colon. Blood and stool samples were taken, and demographic and clinical data were collected.
The study enrolled 253 patients. Almost half (47.4%) were younger than 50 years, and 46.3% were women. They were followed for 12 months, during which 19% developed clinical relapse, defined as a partial Mayo endoscopic score (MES) of greater than 2.
When compared with patients with an MES of 0, the team found that patients with an MES of 1 or greater than or equal to 2 were at higher risk of relapse, with an adjusted hazard ratio of 2.65 and 2.57, respectively.
Interestingly, a lower baseline MES also was associated with a lower risk of relapse, and patients with proctitis were more likely to experience relapse than those with pancolitis.
No impact of histology on relapse risk
Further analysis revealed that there was no association between clinical relapse and age, sex, disease extent, and C-reactive protein, hemoglobin, and albumin levels. However, there was a significant association between relapse and the occurrence of at least one relapse in the 2 years prior to enrollment.
While the mean baseline fecal calprotectin (FC) level was numerically higher in patients who experienced relapse, compared with those who did not (306.9 mcg/g vs. 213.7 mcg/g), the difference was not significant.
FC of greater than 100 mcg/g was, however, significantly associated with relapse, at an odds ratio of 2.26, although the association was no longer significant when using the False Discovery Rate test.
Active histology was no more common among those who experienced relapse than among those who did not. But with regard to histologic factors, the team found that the presence of basal plasmacytosis was associated with clinical relapse, at an adjusted odds ratio of 2.07.
On the other hand, a Geboes Score of greater than or equal to 3.1, indicating the presence of epithelial neutrophils with or without crypt destruction or erosions, was not significantly associated with the risk of relapse, nor with the time to clinical relapse.
Clinical implications
Approached for comment, Miguel Regueiro, MD, chair of the Digestive Disease and Surgery Institute at the Cleveland Clinic, said that this is “the largest prospective study assessing histologic activity or remission to predict future disease relapse in ulcerative colitis.”
He told this news organization that what the findings mean for clinical practice is that “patients who achieve an endoscopic and clinical remission are at a low likelihood of clinical relapse,” and added that “these should be the ‘treat-to-target’ endpoints.”
“Patients who have biopsy evidence, [such as] histologic activity based on the Geboes Score, do not require an escalation of therapy or a change in inflammatory bowel disease therapy,” Dr. Regueiro said.
He noted, however, that one primary question remains: Aside from surveillance of dysplasia, is there a role for biopsy in cases of UC in which the Mayo score is 0?
“In my practice, I still take biopsies from a previously involved colitis segment, even if Mayo 0,” he said.
“If there is histologic activity, I would not increase or optimize the current medications, but I also would not deescalate,” Dr. Regueiro added. “I would keep the patient on a regular surveillance colonoscopy regimen, too.”
No funding for the study has been reported. Dr. Bessissow has relationships with AbbVie, Alimentiv (formerly Robarts), Amgen, Bristol-Myers-Squibb, Ferring, Gilead, Janssen, Merck, Pentax, Pfizer, Roche, Sandoz, Takeda, and Viatris. Other authors have disclosed numerous financial relationships. Dr. Regueiro has disclosed no such relationships.
A version of this article first appeared on Medscape.com.
For patients who experience endoscopic remission of ulcerative colitis (UC), signs of active disease on histology did not affect their risk of clinical relapse, according to a large prospective study that reinforces a low endoscopy score as the treatment target.
In the study of more than 250 patients in endoscopic remission from UC, 19% experienced a clinical relapse within 1 year. The researchers found that a lower baseline endoscopy score was linked to a lower risk of relapse.
While histologic activity, as reflected in the Geboes Score, was not associated with clinical relapse, the presence of basal plasmacytosis independently doubled the risk of relapse.
“Our findings do not support the use of histology as a target for treatment in patients with ulcerative colitis who already achieved clinical and endoscopic remission,” say Talat Bessissow, MD, McGill University Health Center, Montreal, and colleagues.
They add that the results “support the use of the Mayo endoscopic subscore of zero as the optimal target for endoscopic remission.”
Further prospective data are needed to “define the role of histology activity and basal plasmacytosis in the management of ulcerative colitis,” the authors write.
The study was published online in The American Journal of Gastroenterology.
Uncertain role of histology
Dr. Bessissow told this news organization that “some studies have shown that histologic healing is associated with better long-term outcomes and less relapse, but this topic remains controversial because other studies have shown the opposite.”
“Our study does not support histology as a treatment target,” he continued, adding that therapy should not be changed solely on the basis of histology.
Dr. Bessissow clarified that although histology was not associated with less relapse over 1 year of follow-up, the role of histology on other, longer-term outcomes, such as surgery and colorectal cancer, still needs to be studied.
The natural history of UC is characterized by frequent relapse, the authors write, but “treating symptoms alone is not sufficient to prevent long-term complications.”
This led to a shift toward using endoscopic healing as a therapeutic goal, a move that was aided by the advent of novel medical therapies, including biologic agents. Crucially, endoscopic healing is associated with improved long-term outcomes, as well as improved quality of life.
The authors continue, however, that a “significant proportion” of patients experience relapse despite achieving endoscopic healing, which “could be explained in part by the fact that up to 40% of patients in endoscopic healing will have ongoing active histologic disease.”
However, in studies in which histologic activity was an endpoint, results have conflicted, and questions remain as to which parameters to include when assessing histologic activity.
Measuring the predictive values of endoscopy and histology
To investigate further, the researchers conducted a prospective observational study of consecutive adult patients with confirmed UC who presented to an endoscopy unit for colonoscopy for disease assessment or surveillance.
To qualify for the study, the patients’ conditions had to have been in clinical remission for at least 3 months prior to the colonoscopy. They were excluded if they had undergone prior surgical resection, had experienced disease remission for a period of over 10 years, or had used oral or rectal steroids within 90 days, among other criteria.
During an initial colonoscopy, two biopsies were performed, with specimens taken from the rectosigmoid and, when possible, from the right and left colon. Blood and stool samples were taken, and demographic and clinical data were collected.
The study enrolled 253 patients. Almost half (47.4%) were younger than 50 years, and 46.3% were women. They were followed for 12 months, during which 19% developed clinical relapse, defined as a partial Mayo endoscopic score (MES) of greater than 2.
When compared with patients with an MES of 0, the team found that patients with an MES of 1 or greater than or equal to 2 were at higher risk of relapse, with an adjusted hazard ratio of 2.65 and 2.57, respectively.
Interestingly, a lower baseline MES also was associated with a lower risk of relapse, and patients with proctitis were more likely to experience relapse than those with pancolitis.
No impact of histology on relapse risk
Further analysis revealed that there was no association between clinical relapse and age, sex, disease extent, and C-reactive protein, hemoglobin, and albumin levels. However, there was a significant association between relapse and the occurrence of at least one relapse in the 2 years prior to enrollment.
While the mean baseline fecal calprotectin (FC) level was numerically higher in patients who experienced relapse, compared with those who did not (306.9 mcg/g vs. 213.7 mcg/g), the difference was not significant.
FC of greater than 100 mcg/g was, however, significantly associated with relapse, at an odds ratio of 2.26, although the association was no longer significant when using the False Discovery Rate test.
Active histology was no more common among those who experienced relapse than among those who did not. But with regard to histologic factors, the team found that the presence of basal plasmacytosis was associated with clinical relapse, at an adjusted odds ratio of 2.07.
On the other hand, a Geboes Score of greater than or equal to 3.1, indicating the presence of epithelial neutrophils with or without crypt destruction or erosions, was not significantly associated with the risk of relapse, nor with the time to clinical relapse.
Clinical implications
Approached for comment, Miguel Regueiro, MD, chair of the Digestive Disease and Surgery Institute at the Cleveland Clinic, said that this is “the largest prospective study assessing histologic activity or remission to predict future disease relapse in ulcerative colitis.”
He told this news organization that what the findings mean for clinical practice is that “patients who achieve an endoscopic and clinical remission are at a low likelihood of clinical relapse,” and added that “these should be the ‘treat-to-target’ endpoints.”
“Patients who have biopsy evidence, [such as] histologic activity based on the Geboes Score, do not require an escalation of therapy or a change in inflammatory bowel disease therapy,” Dr. Regueiro said.
He noted, however, that one primary question remains: Aside from surveillance of dysplasia, is there a role for biopsy in cases of UC in which the Mayo score is 0?
“In my practice, I still take biopsies from a previously involved colitis segment, even if Mayo 0,” he said.
“If there is histologic activity, I would not increase or optimize the current medications, but I also would not deescalate,” Dr. Regueiro added. “I would keep the patient on a regular surveillance colonoscopy regimen, too.”
No funding for the study has been reported. Dr. Bessissow has relationships with AbbVie, Alimentiv (formerly Robarts), Amgen, Bristol-Myers-Squibb, Ferring, Gilead, Janssen, Merck, Pentax, Pfizer, Roche, Sandoz, Takeda, and Viatris. Other authors have disclosed numerous financial relationships. Dr. Regueiro has disclosed no such relationships.
A version of this article first appeared on Medscape.com.
For patients who experience endoscopic remission of ulcerative colitis (UC), signs of active disease on histology did not affect their risk of clinical relapse, according to a large prospective study that reinforces a low endoscopy score as the treatment target.
In the study of more than 250 patients in endoscopic remission from UC, 19% experienced a clinical relapse within 1 year. The researchers found that a lower baseline endoscopy score was linked to a lower risk of relapse.
While histologic activity, as reflected in the Geboes Score, was not associated with clinical relapse, the presence of basal plasmacytosis independently doubled the risk of relapse.
“Our findings do not support the use of histology as a target for treatment in patients with ulcerative colitis who already achieved clinical and endoscopic remission,” say Talat Bessissow, MD, McGill University Health Center, Montreal, and colleagues.
They add that the results “support the use of the Mayo endoscopic subscore of zero as the optimal target for endoscopic remission.”
Further prospective data are needed to “define the role of histology activity and basal plasmacytosis in the management of ulcerative colitis,” the authors write.
The study was published online in The American Journal of Gastroenterology.
Uncertain role of histology
Dr. Bessissow told this news organization that “some studies have shown that histologic healing is associated with better long-term outcomes and less relapse, but this topic remains controversial because other studies have shown the opposite.”
“Our study does not support histology as a treatment target,” he continued, adding that therapy should not be changed solely on the basis of histology.
Dr. Bessissow clarified that although histology was not associated with less relapse over 1 year of follow-up, the role of histology on other, longer-term outcomes, such as surgery and colorectal cancer, still needs to be studied.
The natural history of UC is characterized by frequent relapse, the authors write, but “treating symptoms alone is not sufficient to prevent long-term complications.”
This led to a shift toward using endoscopic healing as a therapeutic goal, a move that was aided by the advent of novel medical therapies, including biologic agents. Crucially, endoscopic healing is associated with improved long-term outcomes, as well as improved quality of life.
The authors continue, however, that a “significant proportion” of patients experience relapse despite achieving endoscopic healing, which “could be explained in part by the fact that up to 40% of patients in endoscopic healing will have ongoing active histologic disease.”
However, in studies in which histologic activity was an endpoint, results have conflicted, and questions remain as to which parameters to include when assessing histologic activity.
Measuring the predictive values of endoscopy and histology
To investigate further, the researchers conducted a prospective observational study of consecutive adult patients with confirmed UC who presented to an endoscopy unit for colonoscopy for disease assessment or surveillance.
To qualify for the study, the patients’ conditions had to have been in clinical remission for at least 3 months prior to the colonoscopy. They were excluded if they had undergone prior surgical resection, had experienced disease remission for a period of over 10 years, or had used oral or rectal steroids within 90 days, among other criteria.
During an initial colonoscopy, two biopsies were performed, with specimens taken from the rectosigmoid and, when possible, from the right and left colon. Blood and stool samples were taken, and demographic and clinical data were collected.
The study enrolled 253 patients. Almost half (47.4%) were younger than 50 years, and 46.3% were women. They were followed for 12 months, during which 19% developed clinical relapse, defined as a partial Mayo endoscopic score (MES) of greater than 2.
When compared with patients with an MES of 0, the team found that patients with an MES of 1 or greater than or equal to 2 were at higher risk of relapse, with an adjusted hazard ratio of 2.65 and 2.57, respectively.
Interestingly, a lower baseline MES also was associated with a lower risk of relapse, and patients with proctitis were more likely to experience relapse than those with pancolitis.
No impact of histology on relapse risk
Further analysis revealed that there was no association between clinical relapse and age, sex, disease extent, and C-reactive protein, hemoglobin, and albumin levels. However, there was a significant association between relapse and the occurrence of at least one relapse in the 2 years prior to enrollment.
While the mean baseline fecal calprotectin (FC) level was numerically higher in patients who experienced relapse, compared with those who did not (306.9 mcg/g vs. 213.7 mcg/g), the difference was not significant.
FC of greater than 100 mcg/g was, however, significantly associated with relapse, at an odds ratio of 2.26, although the association was no longer significant when using the False Discovery Rate test.
Active histology was no more common among those who experienced relapse than among those who did not. But with regard to histologic factors, the team found that the presence of basal plasmacytosis was associated with clinical relapse, at an adjusted odds ratio of 2.07.
On the other hand, a Geboes Score of greater than or equal to 3.1, indicating the presence of epithelial neutrophils with or without crypt destruction or erosions, was not significantly associated with the risk of relapse, nor with the time to clinical relapse.
Clinical implications
Approached for comment, Miguel Regueiro, MD, chair of the Digestive Disease and Surgery Institute at the Cleveland Clinic, said that this is “the largest prospective study assessing histologic activity or remission to predict future disease relapse in ulcerative colitis.”
He told this news organization that what the findings mean for clinical practice is that “patients who achieve an endoscopic and clinical remission are at a low likelihood of clinical relapse,” and added that “these should be the ‘treat-to-target’ endpoints.”
“Patients who have biopsy evidence, [such as] histologic activity based on the Geboes Score, do not require an escalation of therapy or a change in inflammatory bowel disease therapy,” Dr. Regueiro said.
He noted, however, that one primary question remains: Aside from surveillance of dysplasia, is there a role for biopsy in cases of UC in which the Mayo score is 0?
“In my practice, I still take biopsies from a previously involved colitis segment, even if Mayo 0,” he said.
“If there is histologic activity, I would not increase or optimize the current medications, but I also would not deescalate,” Dr. Regueiro added. “I would keep the patient on a regular surveillance colonoscopy regimen, too.”
No funding for the study has been reported. Dr. Bessissow has relationships with AbbVie, Alimentiv (formerly Robarts), Amgen, Bristol-Myers-Squibb, Ferring, Gilead, Janssen, Merck, Pentax, Pfizer, Roche, Sandoz, Takeda, and Viatris. Other authors have disclosed numerous financial relationships. Dr. Regueiro has disclosed no such relationships.
A version of this article first appeared on Medscape.com.
Comorbidities key to serious infections with IBD treatment
Among biologic agents, vedolizumab (Entyvio) and ustekinumab (Stelara) are associated with lower rates of infection-related hospitalizations than anti-tumor necrosis factor (TNF) agents in older patients with inflammatory bowel disease (IBD), but only if older patients also have comorbidities, U.S. researchers have found.
The researchers examined U.S. health insurance claims for three cohorts – patients with IBD who were treated with anti-TNF agents, vedolizumab, and ustekinumab – and found no overall difference in infection rates or infection-related hospitalizations between the groups.
But in patients with a greater burden of comorbidity, the monoclonal antibodies vedolizumab and ustekinumab were associated with lower rates of infection-related hospitalizations, compared with anti-TNF agents, with 22% less for vedolizumab and 34% less for ustekinumab.
In the “first pharmacoepidemiologic study comparing all approved classes of biologic agents to treat IBD focused on older adults,” the authors say they “demonstrate that comorbidity is a mediator of infections requiring hospitalizations.”
“These data can help counsel older adults who are about to initiate a biologic agent in clinical practice,” they write.
The research was published online in The American Journal of Gastroenterology.
Co-lead author Bharati Kochar, MD, MS, a gastroenterologist at Massachusetts General Hospital, Boston, said that the real question, when we’re seeing an older patient, is which medications are safer.
“Not surprisingly, we found that there was no overall difference in the three classes of medications,” she said, adding that “if you take your healthy older adults without any serious comorbidities, anti-TNF agents are not different in terms of a safety profile.”
With the more selective biologics like vedolizumab and ustekinumab seeming to confer a lower risk for serious infections in patients with comorbidities, Dr. Kochar said the hope is that their study will help doctors feel more confident in prescribing and encourage thinking about the patient in a broader manner beyond chronological age.
Real-world study on older adults with IBD
The authors note that the number of older adults with IBD is rising rapidly. It is estimated that almost 1 million individuals aged 60 years and older in the United States are living with the disease.
They add that there has been a rapid proliferation of treatment options for both Crohn’s disease and ulcerative colitis, but the likelihood of achieving remission may vary by mechanism of immunosuppression.
Older adults have a higher baseline risk for infections than younger adults, regardless of treatment type, the authors underline; yet, older adults with IBD are disproportionately under-represented in clinical trials of IBD therapies.
Recognizing the need for real-world studies focused on older adults, Dr. Kochar and her colleagues gathered claims data from a commercial U.S. health insurance plan totaling nearly 86 million individuals between 2008 and 2019.
They identified patients with IBD aged 60 years or older (average age, 67 years) who had at least one claim for vedolizumab, ustekinumab, or anti-TNF agents, including adalimumab, infliximab, golimumab, or certolizumab pegol.
The cohorts included 2,369 patients treated with anti-TNF agents, 972 who were started on vedolizumab and 352 who were given ustekinumab.
Patients were excluded if they received vedolizumab or ustekinumab during the first 6 months of treatment and were then switched to anti-TNF therapy.
The on-treatment period was defined as starting with the index treatment date and ending with the date of treatment discontinuation. Treatment was required to last more than 90 days.
The overall incidence rates for any infection were similar across the three treatment groups, at 3,606 per 1,000 person-years in the anti-TNF group, 3,748 per 1,000 person-years in patients given vedolizumab, and 3,139 per 1,000 person-years in those treated with ustekinumab.
There were also no significant differences in the rate of infection-related hospitalizations, at a hazard ratio for vedolizumab versus anti-TNF agents of 0.94, and for ustekinumab, again versus anti-TNF agents, of 0.92.
However, the authors found that there was a “significant interaction” between comorbidities and treatment in terms of infection-related hospitalizations.
Among IBD patients older than 60 with a Charlson Comorbidity Index (CCI) score of greater than 1, treatment with vedolizumab and ustekinumab was associated with a significantly lower rate of infection-related hospitalizations versus anti-TNF agents, at hazard ratios of 0.78 and 0.66, respectively.
In contrast, the rates of hospitalization were similar between the treatment groups among patients without significant comorbidity.
Interestingly, patients with ulcerative colitis treated with vedolizumab also had a lower rate of infection versus those given anti-TNF agents, at a hazard ratio of 0.96, while no such difference was seen in patients with Crohn’s disease.
Results will help refine clinical practice
Approached for comment, Dana J. Lukin, MD, PhD, clinical director of translational research at the Jill Roberts Center for Inflammatory Bowel Disease, New York, said the study is limited by the lack of granular data on disease activity.
Moreover, he told this news organization that since it is not a randomized controlled trial, the selection of medications in the claims database may have factored in some of the intangible contraindications to anti-TNF agents.
“It makes sense that comorbidity confers the biggest risk for hospitalization from infections,” Dr. Lukin said, adding that “what is interesting is that there is no difference overall in infection rates between any of the medication classes.”
He said the study therefore “rebuffs the traditional thinking” that, among older adults, anti-TNF agents will be associated with a higher risk of infections per se, “because really it’s specifically among those patients who have more comorbidities.”
Most importantly, Dr. Lukin said that the findings will help to refine clinical practice, as clinicians are specifically tasked with treating the inflammatory bowel disease but are not necessarily focused on comorbidities, which patients accrue more and more as they age.
Dr. Lukin continued that, for patients with comorbid conditions, “we should carefully consider using a non–anti-TNF agent.”
“We should also not be afraid to continue to use anti-TNF agents” in those without comorbidities, he added, as they are “very effective in patients who might need them for their disease-related characteristics.”
The study was supported in part by grants from the National Institutes of Health, the Crohn’s and Colitis Foundation, and the Chleck Family Foundation.
Dr. Lukin declares relationships with Takeda, Abbvie, and Janssen. No other relevant financial relationships were declared.
A version of this article first appeared on Medscape.com.
Among biologic agents, vedolizumab (Entyvio) and ustekinumab (Stelara) are associated with lower rates of infection-related hospitalizations than anti-tumor necrosis factor (TNF) agents in older patients with inflammatory bowel disease (IBD), but only if older patients also have comorbidities, U.S. researchers have found.
The researchers examined U.S. health insurance claims for three cohorts – patients with IBD who were treated with anti-TNF agents, vedolizumab, and ustekinumab – and found no overall difference in infection rates or infection-related hospitalizations between the groups.
But in patients with a greater burden of comorbidity, the monoclonal antibodies vedolizumab and ustekinumab were associated with lower rates of infection-related hospitalizations, compared with anti-TNF agents, with 22% less for vedolizumab and 34% less for ustekinumab.
In the “first pharmacoepidemiologic study comparing all approved classes of biologic agents to treat IBD focused on older adults,” the authors say they “demonstrate that comorbidity is a mediator of infections requiring hospitalizations.”
“These data can help counsel older adults who are about to initiate a biologic agent in clinical practice,” they write.
The research was published online in The American Journal of Gastroenterology.
Co-lead author Bharati Kochar, MD, MS, a gastroenterologist at Massachusetts General Hospital, Boston, said that the real question, when we’re seeing an older patient, is which medications are safer.
“Not surprisingly, we found that there was no overall difference in the three classes of medications,” she said, adding that “if you take your healthy older adults without any serious comorbidities, anti-TNF agents are not different in terms of a safety profile.”
With the more selective biologics like vedolizumab and ustekinumab seeming to confer a lower risk for serious infections in patients with comorbidities, Dr. Kochar said the hope is that their study will help doctors feel more confident in prescribing and encourage thinking about the patient in a broader manner beyond chronological age.
Real-world study on older adults with IBD
The authors note that the number of older adults with IBD is rising rapidly. It is estimated that almost 1 million individuals aged 60 years and older in the United States are living with the disease.
They add that there has been a rapid proliferation of treatment options for both Crohn’s disease and ulcerative colitis, but the likelihood of achieving remission may vary by mechanism of immunosuppression.
Older adults have a higher baseline risk for infections than younger adults, regardless of treatment type, the authors underline; yet, older adults with IBD are disproportionately under-represented in clinical trials of IBD therapies.
Recognizing the need for real-world studies focused on older adults, Dr. Kochar and her colleagues gathered claims data from a commercial U.S. health insurance plan totaling nearly 86 million individuals between 2008 and 2019.
They identified patients with IBD aged 60 years or older (average age, 67 years) who had at least one claim for vedolizumab, ustekinumab, or anti-TNF agents, including adalimumab, infliximab, golimumab, or certolizumab pegol.
The cohorts included 2,369 patients treated with anti-TNF agents, 972 who were started on vedolizumab and 352 who were given ustekinumab.
Patients were excluded if they received vedolizumab or ustekinumab during the first 6 months of treatment and were then switched to anti-TNF therapy.
The on-treatment period was defined as starting with the index treatment date and ending with the date of treatment discontinuation. Treatment was required to last more than 90 days.
The overall incidence rates for any infection were similar across the three treatment groups, at 3,606 per 1,000 person-years in the anti-TNF group, 3,748 per 1,000 person-years in patients given vedolizumab, and 3,139 per 1,000 person-years in those treated with ustekinumab.
There were also no significant differences in the rate of infection-related hospitalizations, at a hazard ratio for vedolizumab versus anti-TNF agents of 0.94, and for ustekinumab, again versus anti-TNF agents, of 0.92.
However, the authors found that there was a “significant interaction” between comorbidities and treatment in terms of infection-related hospitalizations.
Among IBD patients older than 60 with a Charlson Comorbidity Index (CCI) score of greater than 1, treatment with vedolizumab and ustekinumab was associated with a significantly lower rate of infection-related hospitalizations versus anti-TNF agents, at hazard ratios of 0.78 and 0.66, respectively.
In contrast, the rates of hospitalization were similar between the treatment groups among patients without significant comorbidity.
Interestingly, patients with ulcerative colitis treated with vedolizumab also had a lower rate of infection versus those given anti-TNF agents, at a hazard ratio of 0.96, while no such difference was seen in patients with Crohn’s disease.
Results will help refine clinical practice
Approached for comment, Dana J. Lukin, MD, PhD, clinical director of translational research at the Jill Roberts Center for Inflammatory Bowel Disease, New York, said the study is limited by the lack of granular data on disease activity.
Moreover, he told this news organization that since it is not a randomized controlled trial, the selection of medications in the claims database may have factored in some of the intangible contraindications to anti-TNF agents.
“It makes sense that comorbidity confers the biggest risk for hospitalization from infections,” Dr. Lukin said, adding that “what is interesting is that there is no difference overall in infection rates between any of the medication classes.”
He said the study therefore “rebuffs the traditional thinking” that, among older adults, anti-TNF agents will be associated with a higher risk of infections per se, “because really it’s specifically among those patients who have more comorbidities.”
Most importantly, Dr. Lukin said that the findings will help to refine clinical practice, as clinicians are specifically tasked with treating the inflammatory bowel disease but are not necessarily focused on comorbidities, which patients accrue more and more as they age.
Dr. Lukin continued that, for patients with comorbid conditions, “we should carefully consider using a non–anti-TNF agent.”
“We should also not be afraid to continue to use anti-TNF agents” in those without comorbidities, he added, as they are “very effective in patients who might need them for their disease-related characteristics.”
The study was supported in part by grants from the National Institutes of Health, the Crohn’s and Colitis Foundation, and the Chleck Family Foundation.
Dr. Lukin declares relationships with Takeda, Abbvie, and Janssen. No other relevant financial relationships were declared.
A version of this article first appeared on Medscape.com.
Among biologic agents, vedolizumab (Entyvio) and ustekinumab (Stelara) are associated with lower rates of infection-related hospitalizations than anti-tumor necrosis factor (TNF) agents in older patients with inflammatory bowel disease (IBD), but only if older patients also have comorbidities, U.S. researchers have found.
The researchers examined U.S. health insurance claims for three cohorts – patients with IBD who were treated with anti-TNF agents, vedolizumab, and ustekinumab – and found no overall difference in infection rates or infection-related hospitalizations between the groups.
But in patients with a greater burden of comorbidity, the monoclonal antibodies vedolizumab and ustekinumab were associated with lower rates of infection-related hospitalizations, compared with anti-TNF agents, with 22% less for vedolizumab and 34% less for ustekinumab.
In the “first pharmacoepidemiologic study comparing all approved classes of biologic agents to treat IBD focused on older adults,” the authors say they “demonstrate that comorbidity is a mediator of infections requiring hospitalizations.”
“These data can help counsel older adults who are about to initiate a biologic agent in clinical practice,” they write.
The research was published online in The American Journal of Gastroenterology.
Co-lead author Bharati Kochar, MD, MS, a gastroenterologist at Massachusetts General Hospital, Boston, said that the real question, when we’re seeing an older patient, is which medications are safer.
“Not surprisingly, we found that there was no overall difference in the three classes of medications,” she said, adding that “if you take your healthy older adults without any serious comorbidities, anti-TNF agents are not different in terms of a safety profile.”
With the more selective biologics like vedolizumab and ustekinumab seeming to confer a lower risk for serious infections in patients with comorbidities, Dr. Kochar said the hope is that their study will help doctors feel more confident in prescribing and encourage thinking about the patient in a broader manner beyond chronological age.
Real-world study on older adults with IBD
The authors note that the number of older adults with IBD is rising rapidly. It is estimated that almost 1 million individuals aged 60 years and older in the United States are living with the disease.
They add that there has been a rapid proliferation of treatment options for both Crohn’s disease and ulcerative colitis, but the likelihood of achieving remission may vary by mechanism of immunosuppression.
Older adults have a higher baseline risk for infections than younger adults, regardless of treatment type, the authors underline; yet, older adults with IBD are disproportionately under-represented in clinical trials of IBD therapies.
Recognizing the need for real-world studies focused on older adults, Dr. Kochar and her colleagues gathered claims data from a commercial U.S. health insurance plan totaling nearly 86 million individuals between 2008 and 2019.
They identified patients with IBD aged 60 years or older (average age, 67 years) who had at least one claim for vedolizumab, ustekinumab, or anti-TNF agents, including adalimumab, infliximab, golimumab, or certolizumab pegol.
The cohorts included 2,369 patients treated with anti-TNF agents, 972 who were started on vedolizumab and 352 who were given ustekinumab.
Patients were excluded if they received vedolizumab or ustekinumab during the first 6 months of treatment and were then switched to anti-TNF therapy.
The on-treatment period was defined as starting with the index treatment date and ending with the date of treatment discontinuation. Treatment was required to last more than 90 days.
The overall incidence rates for any infection were similar across the three treatment groups, at 3,606 per 1,000 person-years in the anti-TNF group, 3,748 per 1,000 person-years in patients given vedolizumab, and 3,139 per 1,000 person-years in those treated with ustekinumab.
There were also no significant differences in the rate of infection-related hospitalizations, at a hazard ratio for vedolizumab versus anti-TNF agents of 0.94, and for ustekinumab, again versus anti-TNF agents, of 0.92.
However, the authors found that there was a “significant interaction” between comorbidities and treatment in terms of infection-related hospitalizations.
Among IBD patients older than 60 with a Charlson Comorbidity Index (CCI) score of greater than 1, treatment with vedolizumab and ustekinumab was associated with a significantly lower rate of infection-related hospitalizations versus anti-TNF agents, at hazard ratios of 0.78 and 0.66, respectively.
In contrast, the rates of hospitalization were similar between the treatment groups among patients without significant comorbidity.
Interestingly, patients with ulcerative colitis treated with vedolizumab also had a lower rate of infection versus those given anti-TNF agents, at a hazard ratio of 0.96, while no such difference was seen in patients with Crohn’s disease.
Results will help refine clinical practice
Approached for comment, Dana J. Lukin, MD, PhD, clinical director of translational research at the Jill Roberts Center for Inflammatory Bowel Disease, New York, said the study is limited by the lack of granular data on disease activity.
Moreover, he told this news organization that since it is not a randomized controlled trial, the selection of medications in the claims database may have factored in some of the intangible contraindications to anti-TNF agents.
“It makes sense that comorbidity confers the biggest risk for hospitalization from infections,” Dr. Lukin said, adding that “what is interesting is that there is no difference overall in infection rates between any of the medication classes.”
He said the study therefore “rebuffs the traditional thinking” that, among older adults, anti-TNF agents will be associated with a higher risk of infections per se, “because really it’s specifically among those patients who have more comorbidities.”
Most importantly, Dr. Lukin said that the findings will help to refine clinical practice, as clinicians are specifically tasked with treating the inflammatory bowel disease but are not necessarily focused on comorbidities, which patients accrue more and more as they age.
Dr. Lukin continued that, for patients with comorbid conditions, “we should carefully consider using a non–anti-TNF agent.”
“We should also not be afraid to continue to use anti-TNF agents” in those without comorbidities, he added, as they are “very effective in patients who might need them for their disease-related characteristics.”
The study was supported in part by grants from the National Institutes of Health, the Crohn’s and Colitis Foundation, and the Chleck Family Foundation.
Dr. Lukin declares relationships with Takeda, Abbvie, and Janssen. No other relevant financial relationships were declared.
A version of this article first appeared on Medscape.com.
FROM THE AMERICAN JOURNAL OF GASTROENTEROLOGY
New update focuses on NAFLD in lean people
Ongoing follow-up and lifestyle interventions are needed in lean patients with nonalcoholic fatty liver disease (NAFLD), suggests a panel of experts in a recent review.
They also urge screening for NAFLD in individuals who are older than 40 years with type 2 diabetes, even if they are not overweight.
NAFLD is a leading cause of chronic liver disease that affects more than 25% of the United States and worldwide populations, note lead author Michelle T. Long, MD, Boston Medical Center, Boston University, and colleagues.
They add that around one-quarter of those affected have nonalcoholic steatohepatitis, which is associated with significant morbidity and mortality due to complications of liver cirrhosis, hepatic decompensation, and hepatocellular carcinoma.
Although NAFLD occurs primarily in individuals with obesity or type 2 diabetes, between 7%-20% have a lean body habitus, they write.
There are differences in rates of disease progression, associated conditions, and diagnostic and management approaches between lean and non-lean patients, the authors note, but there is limited guidance on the appropriate clinical evaluation of the former group.
The American Gastroenterological Association therefore commissioned an expert review to provide best practice advice on key clinical issues relating to the diagnosis, risk stratification, and treatment of NAFLD in lean individuals.
Their review was published online in Gastroenterology.
Evidence-based approaches
The 15 best practice advice statements covered a wide range of clinical areas, first defining lean as a body mass index (BMI) less than 25 in non-Asian persons and less than 23 in Asian persons.
The authors go on to stipulate, for example, that lean individuals in the general population should not be screened for NAFLD but that screening should be considered for individuals older than 40 years with type 2 diabetes.
More broadly, they write that the condition should be considered in lean individuals with metabolic diseases, such as type 2 diabetes, dyslipidemia, and hypertension, as well as elevated values on liver biochemical tests or incidentally noted hepatic steatosis.
After other causes of liver diseases are ruled out, the authors note that clinicians should consider liver biopsy as the reference test if uncertainties remain about liver injury causes and/or liver fibrosis staging.
They also write that the NAFLD fibrosis score and Fibrosis-4 score, along with imaging techniques, may be used as alternatives to biopsy for staging and during follow-up.
The authors, who provide a diagnosis and management algorithm to aid clinicians, suggest that lean patients with NAFLD follow lifestyle interventions, such as exercise, diet modification, and avoidance of fructose- and sugar-sweetened drinks, to achieve weight loss of 3%-5%.
Vitamin E may be considered, they continue, in patients with biopsy-confirmed nonalcoholic steatohepatitis but without type 2 diabetes or cirrhosis. Additionally, oral pioglitazone may be considered in lean persons with biopsy-confirmed nonalcoholic steatohepatitis without cirrhosis.
In contrast, they write that the role of glucagonlike peptide 1 agonists and sodium-glucose cotransporter 2 inhibitors requires further investigation.
The advice also says that lean patients with NAFLD should be routinely evaluated for comorbid conditions, such as type 2 diabetes, dyslipidemia, and hypertension, and risk-stratified for hepatic fibrosis to identify those with advanced fibrosis or cirrhosis.
For lean patients with NAFLD and clinical markers compatible with liver cirrhosis, twice-yearly surveillance for hepatocellular carcinoma is also advised.
Fatty liver disease in lean people with metabolic conditions
Approached for comment, Liyun Yuan, MD, PhD, assistant professor of clinical medicine, University of Southern California, Los Angeles, said it is very important to have uniform guidelines for general practitioners and other specialties on NAFLD in lean individuals.
Dr. Yuan, who was not involved in the review, told this news organization that it is crucial to raise awareness of NAFLD, just like awareness of breast cancer screening among women of a certain age was increased, so that individuals are screened for metabolic conditions regardless of whether they have obesity or overweight.
Zobair Younossi, MD, MPH, professor of medicine, Virginia Commonwealth University, Inova Campus, Falls Church, Va., added that there is a lack of awareness that NAFLD occurs in lean individuals, especially in those who have diabetes.
He said in an interview that although it is accurate to define individuals as being lean in terms of their BMI, the best way is to look not only at BMI but also at waist circumference.
Dr. Younossi said that he and his colleagues have shown that when BMI is combined with waist circumference, the prediction of mortality risk in NAFLD is affected, such that lean individuals with an obese waist circumference have a higher risk for all-cause mortality.
Dr. Long is supported in part by the National Institute of Diabetes and Digestive and Kidney Diseases, Doris Duke Charitable Foundation, Gilead Sciences Research Scholars Award, Boston University School of Medicine Department of Medicine Career Investment Award, and Boston University Clinical Translational Science Institute. Dr. Long declares relationships with Novo Nordisk, Echosens Corporation, and Gilead Sciences. Dr. Yuan declares relationships with Genfit, Intercept, and Gilead Sciences. Dr. Younossi declares no relevant relationships.
A version of this article first appeared on Medscape.com.
*This article was updated on July 27, 2022.
Ongoing follow-up and lifestyle interventions are needed in lean patients with nonalcoholic fatty liver disease (NAFLD), suggests a panel of experts in a recent review.
They also urge screening for NAFLD in individuals who are older than 40 years with type 2 diabetes, even if they are not overweight.
NAFLD is a leading cause of chronic liver disease that affects more than 25% of the United States and worldwide populations, note lead author Michelle T. Long, MD, Boston Medical Center, Boston University, and colleagues.
They add that around one-quarter of those affected have nonalcoholic steatohepatitis, which is associated with significant morbidity and mortality due to complications of liver cirrhosis, hepatic decompensation, and hepatocellular carcinoma.
Although NAFLD occurs primarily in individuals with obesity or type 2 diabetes, between 7%-20% have a lean body habitus, they write.
There are differences in rates of disease progression, associated conditions, and diagnostic and management approaches between lean and non-lean patients, the authors note, but there is limited guidance on the appropriate clinical evaluation of the former group.
The American Gastroenterological Association therefore commissioned an expert review to provide best practice advice on key clinical issues relating to the diagnosis, risk stratification, and treatment of NAFLD in lean individuals.
Their review was published online in Gastroenterology.
Evidence-based approaches
The 15 best practice advice statements covered a wide range of clinical areas, first defining lean as a body mass index (BMI) less than 25 in non-Asian persons and less than 23 in Asian persons.
The authors go on to stipulate, for example, that lean individuals in the general population should not be screened for NAFLD but that screening should be considered for individuals older than 40 years with type 2 diabetes.
More broadly, they write that the condition should be considered in lean individuals with metabolic diseases, such as type 2 diabetes, dyslipidemia, and hypertension, as well as elevated values on liver biochemical tests or incidentally noted hepatic steatosis.
After other causes of liver diseases are ruled out, the authors note that clinicians should consider liver biopsy as the reference test if uncertainties remain about liver injury causes and/or liver fibrosis staging.
They also write that the NAFLD fibrosis score and Fibrosis-4 score, along with imaging techniques, may be used as alternatives to biopsy for staging and during follow-up.
The authors, who provide a diagnosis and management algorithm to aid clinicians, suggest that lean patients with NAFLD follow lifestyle interventions, such as exercise, diet modification, and avoidance of fructose- and sugar-sweetened drinks, to achieve weight loss of 3%-5%.
Vitamin E may be considered, they continue, in patients with biopsy-confirmed nonalcoholic steatohepatitis but without type 2 diabetes or cirrhosis. Additionally, oral pioglitazone may be considered in lean persons with biopsy-confirmed nonalcoholic steatohepatitis without cirrhosis.
In contrast, they write that the role of glucagonlike peptide 1 agonists and sodium-glucose cotransporter 2 inhibitors requires further investigation.
The advice also says that lean patients with NAFLD should be routinely evaluated for comorbid conditions, such as type 2 diabetes, dyslipidemia, and hypertension, and risk-stratified for hepatic fibrosis to identify those with advanced fibrosis or cirrhosis.
For lean patients with NAFLD and clinical markers compatible with liver cirrhosis, twice-yearly surveillance for hepatocellular carcinoma is also advised.
Fatty liver disease in lean people with metabolic conditions
Approached for comment, Liyun Yuan, MD, PhD, assistant professor of clinical medicine, University of Southern California, Los Angeles, said it is very important to have uniform guidelines for general practitioners and other specialties on NAFLD in lean individuals.
Dr. Yuan, who was not involved in the review, told this news organization that it is crucial to raise awareness of NAFLD, just like awareness of breast cancer screening among women of a certain age was increased, so that individuals are screened for metabolic conditions regardless of whether they have obesity or overweight.
Zobair Younossi, MD, MPH, professor of medicine, Virginia Commonwealth University, Inova Campus, Falls Church, Va., added that there is a lack of awareness that NAFLD occurs in lean individuals, especially in those who have diabetes.
He said in an interview that although it is accurate to define individuals as being lean in terms of their BMI, the best way is to look not only at BMI but also at waist circumference.
Dr. Younossi said that he and his colleagues have shown that when BMI is combined with waist circumference, the prediction of mortality risk in NAFLD is affected, such that lean individuals with an obese waist circumference have a higher risk for all-cause mortality.
Dr. Long is supported in part by the National Institute of Diabetes and Digestive and Kidney Diseases, Doris Duke Charitable Foundation, Gilead Sciences Research Scholars Award, Boston University School of Medicine Department of Medicine Career Investment Award, and Boston University Clinical Translational Science Institute. Dr. Long declares relationships with Novo Nordisk, Echosens Corporation, and Gilead Sciences. Dr. Yuan declares relationships with Genfit, Intercept, and Gilead Sciences. Dr. Younossi declares no relevant relationships.
A version of this article first appeared on Medscape.com.
*This article was updated on July 27, 2022.
Ongoing follow-up and lifestyle interventions are needed in lean patients with nonalcoholic fatty liver disease (NAFLD), suggests a panel of experts in a recent review.
They also urge screening for NAFLD in individuals who are older than 40 years with type 2 diabetes, even if they are not overweight.
NAFLD is a leading cause of chronic liver disease that affects more than 25% of the United States and worldwide populations, note lead author Michelle T. Long, MD, Boston Medical Center, Boston University, and colleagues.
They add that around one-quarter of those affected have nonalcoholic steatohepatitis, which is associated with significant morbidity and mortality due to complications of liver cirrhosis, hepatic decompensation, and hepatocellular carcinoma.
Although NAFLD occurs primarily in individuals with obesity or type 2 diabetes, between 7%-20% have a lean body habitus, they write.
There are differences in rates of disease progression, associated conditions, and diagnostic and management approaches between lean and non-lean patients, the authors note, but there is limited guidance on the appropriate clinical evaluation of the former group.
The American Gastroenterological Association therefore commissioned an expert review to provide best practice advice on key clinical issues relating to the diagnosis, risk stratification, and treatment of NAFLD in lean individuals.
Their review was published online in Gastroenterology.
Evidence-based approaches
The 15 best practice advice statements covered a wide range of clinical areas, first defining lean as a body mass index (BMI) less than 25 in non-Asian persons and less than 23 in Asian persons.
The authors go on to stipulate, for example, that lean individuals in the general population should not be screened for NAFLD but that screening should be considered for individuals older than 40 years with type 2 diabetes.
More broadly, they write that the condition should be considered in lean individuals with metabolic diseases, such as type 2 diabetes, dyslipidemia, and hypertension, as well as elevated values on liver biochemical tests or incidentally noted hepatic steatosis.
After other causes of liver diseases are ruled out, the authors note that clinicians should consider liver biopsy as the reference test if uncertainties remain about liver injury causes and/or liver fibrosis staging.
They also write that the NAFLD fibrosis score and Fibrosis-4 score, along with imaging techniques, may be used as alternatives to biopsy for staging and during follow-up.
The authors, who provide a diagnosis and management algorithm to aid clinicians, suggest that lean patients with NAFLD follow lifestyle interventions, such as exercise, diet modification, and avoidance of fructose- and sugar-sweetened drinks, to achieve weight loss of 3%-5%.
Vitamin E may be considered, they continue, in patients with biopsy-confirmed nonalcoholic steatohepatitis but without type 2 diabetes or cirrhosis. Additionally, oral pioglitazone may be considered in lean persons with biopsy-confirmed nonalcoholic steatohepatitis without cirrhosis.
In contrast, they write that the role of glucagonlike peptide 1 agonists and sodium-glucose cotransporter 2 inhibitors requires further investigation.
The advice also says that lean patients with NAFLD should be routinely evaluated for comorbid conditions, such as type 2 diabetes, dyslipidemia, and hypertension, and risk-stratified for hepatic fibrosis to identify those with advanced fibrosis or cirrhosis.
For lean patients with NAFLD and clinical markers compatible with liver cirrhosis, twice-yearly surveillance for hepatocellular carcinoma is also advised.
Fatty liver disease in lean people with metabolic conditions
Approached for comment, Liyun Yuan, MD, PhD, assistant professor of clinical medicine, University of Southern California, Los Angeles, said it is very important to have uniform guidelines for general practitioners and other specialties on NAFLD in lean individuals.
Dr. Yuan, who was not involved in the review, told this news organization that it is crucial to raise awareness of NAFLD, just like awareness of breast cancer screening among women of a certain age was increased, so that individuals are screened for metabolic conditions regardless of whether they have obesity or overweight.
Zobair Younossi, MD, MPH, professor of medicine, Virginia Commonwealth University, Inova Campus, Falls Church, Va., added that there is a lack of awareness that NAFLD occurs in lean individuals, especially in those who have diabetes.
He said in an interview that although it is accurate to define individuals as being lean in terms of their BMI, the best way is to look not only at BMI but also at waist circumference.
Dr. Younossi said that he and his colleagues have shown that when BMI is combined with waist circumference, the prediction of mortality risk in NAFLD is affected, such that lean individuals with an obese waist circumference have a higher risk for all-cause mortality.
Dr. Long is supported in part by the National Institute of Diabetes and Digestive and Kidney Diseases, Doris Duke Charitable Foundation, Gilead Sciences Research Scholars Award, Boston University School of Medicine Department of Medicine Career Investment Award, and Boston University Clinical Translational Science Institute. Dr. Long declares relationships with Novo Nordisk, Echosens Corporation, and Gilead Sciences. Dr. Yuan declares relationships with Genfit, Intercept, and Gilead Sciences. Dr. Younossi declares no relevant relationships.
A version of this article first appeared on Medscape.com.
*This article was updated on July 27, 2022.
FROM GASTROENTEROLOGY
U.S. hot, cold spots of young-onset CRC may help target interventions
The so-called hot and cold spots of mortality from young-onset CRC differed slightly for people younger than 50 and those younger than 35, report the researchers, who say such studies may lead to better understanding of the underlying factors as well as to targeted interventions.
The authors suggest that deaths in the youngest young-onset CRC individuals “may be driven by a distinct set of factors, compared with deaths among older young-onset CRC and average-onset CRC patients.”
They add that “unmeasured factors ... may drive anomalous young-onset CRC mortality rates, either independently or in conjunction with demographic [and] modifiable variables accounted for here.”
The research was published online in Gastroenterology.
Incidence, mortality rates on the rise
The incidence and mortality rates of young-onset CRC have been increasing for decades, the authors write, but it has only recently begun to attract public health attention.
Risk factors and prognostic indicators, such as smoking, obesity, alcohol consumption, diabetes, sex, race, and socioeconomic factors, have been implicated in the development of the condition.
Geospatial distribution of young-onset CRC adds an “important [layer] for understanding the underlying drivers of mortality and allocating public health resources,” the authors write.
It is “too soon” to draw conclusions about the cause of the hot and cold spots, cautioned senior author Stephanie L. Schmit, PhD, vice chair of the Genomic Medicine Institute at the Lerner Research Institute, Cleveland Clinic.
Speaking to this news organization, she said, “Additional factors like proximity to primary care, gastroenterology, and cancer care facilities or novel environmental exposures may contribute to hot spots.”
On the other hand, “lifestyle factors like diet and exercise might contribute to some extent to cold spots,” she added.
While Dr. Schmit said it would be “challenging” to replicate the findings nationally, “further analyses at more granular geographic levels would be incredibly helpful.”
Exploring the geographical distribution
To explore the geographical distribution of young-onset CRC mortality, the researchers gathered 20 years of data on more than 1 million CRC deaths from 3,036 U.S. counties. With aggregated county-level information from 1999 to 2019, they derived mortality rates from CDC WONDER underlying cause of death data.
Over the study period, there were 69,976 deaths from CRC among individuals diagnosed before age 50, including 7,325 persons diagnosed younger than 35. Most CRC deaths (1,033,541) occurred in people diagnosed at age 50 and older.
The researchers calculated an average county-level young-onset CRC mortality rate of 1.78 deaths per 100,000 population, compared with a CRC mortality rate of 56.82 per 100,000 population among individuals 50 and older.
Overall, for individuals younger than 50 at diagnosis, the researchers found two hot spots – in the Southeast (relative risk, 1.24) and in the Great Lakes region (RR, 1.10). They identified cold spots in lower Wisconsin (RR, 0.87), the Northeast (RR, 0.92), southwest Texas (RR, 0.90), and Western counties more broadly, including Alaska (RR, 0.82).
Further analysis of those diagnosed when younger than 35 revealed two significant young-onset CRC mortality hot spots – in the Northeast (RR, 1.25) and the upper Midwest (RR, 1.11). In this youngest group, the team also found three significant cold spots – in the Southwest (RR, 0.74), in California (RR, 0.78), and in the Mountain West (RR, 0.82).
Among those aged 35-49 years at diagnosis, researchers found three hot spots – two in the Southeast (RR,1.20 and 1.16) and in the Great Lakes region (RR, 1.12). Several cold spots emerged from the mortality data on young-onset CRC in this age group – in the Pacific/Mountain West (RR, 0.90), in California (RR, 0.82), southern Texas (RR, 0.89), and the Southwest more broadly (RR, 0.86).
“Though cold spots were similar across strata, young-onset CRC hot spots shifted southward in the 35-49 age stratum in comparison to the less than 35 group,” the team notes.
They acknowledge several limitations to the study, including its “ecological nature” and the lack of adjustment for stage at diagnosis.
In comments to this news organization, Andrew T. Chan, MD, MPH, of Massachusetts General Hospital and Harvard Medical School, Boston, said the approach used by the researchers was “very interesting.”
Dr. Chan said that this is “one of the first studies that has given us insight into whether there is potential geographic variation in the incidence of young-onset colorectal cancer.”
This, he continued, is “very helpful in terms of thinking about potential risk factors for early-onset cancer and giving us more information about where we might want to focus our efforts in terms of prevention.”
Dr. Chan added that another interesting aspect of the study was that “the patterns might be different, depending on how you define early-onset cancer,” whether as “very-early onset,” defined as onset in those younger than 35, or the “less stringent definition” of 35-49 years.
He said that, “within the group that we’re calling very-early onset, there may be enriched factors,” compared with people who are “a little bit older.”
The research was supported by a National Cancer Institute of the National Institutes of Health grant to Case Comprehensive Cancer Center. Dr. Schmit reports no relevant financial relationships. Other authors have relationships with Exelixis, Tempus, Olympus, Anthos, Bayer, BMS, Janssen, Nektar Therapeutics, Pfizer, Sanofi, and WebMD/Medscape. Dr. Chan reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The so-called hot and cold spots of mortality from young-onset CRC differed slightly for people younger than 50 and those younger than 35, report the researchers, who say such studies may lead to better understanding of the underlying factors as well as to targeted interventions.
The authors suggest that deaths in the youngest young-onset CRC individuals “may be driven by a distinct set of factors, compared with deaths among older young-onset CRC and average-onset CRC patients.”
They add that “unmeasured factors ... may drive anomalous young-onset CRC mortality rates, either independently or in conjunction with demographic [and] modifiable variables accounted for here.”
The research was published online in Gastroenterology.
Incidence, mortality rates on the rise
The incidence and mortality rates of young-onset CRC have been increasing for decades, the authors write, but it has only recently begun to attract public health attention.
Risk factors and prognostic indicators, such as smoking, obesity, alcohol consumption, diabetes, sex, race, and socioeconomic factors, have been implicated in the development of the condition.
Geospatial distribution of young-onset CRC adds an “important [layer] for understanding the underlying drivers of mortality and allocating public health resources,” the authors write.
It is “too soon” to draw conclusions about the cause of the hot and cold spots, cautioned senior author Stephanie L. Schmit, PhD, vice chair of the Genomic Medicine Institute at the Lerner Research Institute, Cleveland Clinic.
Speaking to this news organization, she said, “Additional factors like proximity to primary care, gastroenterology, and cancer care facilities or novel environmental exposures may contribute to hot spots.”
On the other hand, “lifestyle factors like diet and exercise might contribute to some extent to cold spots,” she added.
While Dr. Schmit said it would be “challenging” to replicate the findings nationally, “further analyses at more granular geographic levels would be incredibly helpful.”
Exploring the geographical distribution
To explore the geographical distribution of young-onset CRC mortality, the researchers gathered 20 years of data on more than 1 million CRC deaths from 3,036 U.S. counties. With aggregated county-level information from 1999 to 2019, they derived mortality rates from CDC WONDER underlying cause of death data.
Over the study period, there were 69,976 deaths from CRC among individuals diagnosed before age 50, including 7,325 persons diagnosed younger than 35. Most CRC deaths (1,033,541) occurred in people diagnosed at age 50 and older.
The researchers calculated an average county-level young-onset CRC mortality rate of 1.78 deaths per 100,000 population, compared with a CRC mortality rate of 56.82 per 100,000 population among individuals 50 and older.
Overall, for individuals younger than 50 at diagnosis, the researchers found two hot spots – in the Southeast (relative risk, 1.24) and in the Great Lakes region (RR, 1.10). They identified cold spots in lower Wisconsin (RR, 0.87), the Northeast (RR, 0.92), southwest Texas (RR, 0.90), and Western counties more broadly, including Alaska (RR, 0.82).
Further analysis of those diagnosed when younger than 35 revealed two significant young-onset CRC mortality hot spots – in the Northeast (RR, 1.25) and the upper Midwest (RR, 1.11). In this youngest group, the team also found three significant cold spots – in the Southwest (RR, 0.74), in California (RR, 0.78), and in the Mountain West (RR, 0.82).
Among those aged 35-49 years at diagnosis, researchers found three hot spots – two in the Southeast (RR,1.20 and 1.16) and in the Great Lakes region (RR, 1.12). Several cold spots emerged from the mortality data on young-onset CRC in this age group – in the Pacific/Mountain West (RR, 0.90), in California (RR, 0.82), southern Texas (RR, 0.89), and the Southwest more broadly (RR, 0.86).
“Though cold spots were similar across strata, young-onset CRC hot spots shifted southward in the 35-49 age stratum in comparison to the less than 35 group,” the team notes.
They acknowledge several limitations to the study, including its “ecological nature” and the lack of adjustment for stage at diagnosis.
In comments to this news organization, Andrew T. Chan, MD, MPH, of Massachusetts General Hospital and Harvard Medical School, Boston, said the approach used by the researchers was “very interesting.”
Dr. Chan said that this is “one of the first studies that has given us insight into whether there is potential geographic variation in the incidence of young-onset colorectal cancer.”
This, he continued, is “very helpful in terms of thinking about potential risk factors for early-onset cancer and giving us more information about where we might want to focus our efforts in terms of prevention.”
Dr. Chan added that another interesting aspect of the study was that “the patterns might be different, depending on how you define early-onset cancer,” whether as “very-early onset,” defined as onset in those younger than 35, or the “less stringent definition” of 35-49 years.
He said that, “within the group that we’re calling very-early onset, there may be enriched factors,” compared with people who are “a little bit older.”
The research was supported by a National Cancer Institute of the National Institutes of Health grant to Case Comprehensive Cancer Center. Dr. Schmit reports no relevant financial relationships. Other authors have relationships with Exelixis, Tempus, Olympus, Anthos, Bayer, BMS, Janssen, Nektar Therapeutics, Pfizer, Sanofi, and WebMD/Medscape. Dr. Chan reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The so-called hot and cold spots of mortality from young-onset CRC differed slightly for people younger than 50 and those younger than 35, report the researchers, who say such studies may lead to better understanding of the underlying factors as well as to targeted interventions.
The authors suggest that deaths in the youngest young-onset CRC individuals “may be driven by a distinct set of factors, compared with deaths among older young-onset CRC and average-onset CRC patients.”
They add that “unmeasured factors ... may drive anomalous young-onset CRC mortality rates, either independently or in conjunction with demographic [and] modifiable variables accounted for here.”
The research was published online in Gastroenterology.
Incidence, mortality rates on the rise
The incidence and mortality rates of young-onset CRC have been increasing for decades, the authors write, but it has only recently begun to attract public health attention.
Risk factors and prognostic indicators, such as smoking, obesity, alcohol consumption, diabetes, sex, race, and socioeconomic factors, have been implicated in the development of the condition.
Geospatial distribution of young-onset CRC adds an “important [layer] for understanding the underlying drivers of mortality and allocating public health resources,” the authors write.
It is “too soon” to draw conclusions about the cause of the hot and cold spots, cautioned senior author Stephanie L. Schmit, PhD, vice chair of the Genomic Medicine Institute at the Lerner Research Institute, Cleveland Clinic.
Speaking to this news organization, she said, “Additional factors like proximity to primary care, gastroenterology, and cancer care facilities or novel environmental exposures may contribute to hot spots.”
On the other hand, “lifestyle factors like diet and exercise might contribute to some extent to cold spots,” she added.
While Dr. Schmit said it would be “challenging” to replicate the findings nationally, “further analyses at more granular geographic levels would be incredibly helpful.”
Exploring the geographical distribution
To explore the geographical distribution of young-onset CRC mortality, the researchers gathered 20 years of data on more than 1 million CRC deaths from 3,036 U.S. counties. With aggregated county-level information from 1999 to 2019, they derived mortality rates from CDC WONDER underlying cause of death data.
Over the study period, there were 69,976 deaths from CRC among individuals diagnosed before age 50, including 7,325 persons diagnosed younger than 35. Most CRC deaths (1,033,541) occurred in people diagnosed at age 50 and older.
The researchers calculated an average county-level young-onset CRC mortality rate of 1.78 deaths per 100,000 population, compared with a CRC mortality rate of 56.82 per 100,000 population among individuals 50 and older.
Overall, for individuals younger than 50 at diagnosis, the researchers found two hot spots – in the Southeast (relative risk, 1.24) and in the Great Lakes region (RR, 1.10). They identified cold spots in lower Wisconsin (RR, 0.87), the Northeast (RR, 0.92), southwest Texas (RR, 0.90), and Western counties more broadly, including Alaska (RR, 0.82).
Further analysis of those diagnosed when younger than 35 revealed two significant young-onset CRC mortality hot spots – in the Northeast (RR, 1.25) and the upper Midwest (RR, 1.11). In this youngest group, the team also found three significant cold spots – in the Southwest (RR, 0.74), in California (RR, 0.78), and in the Mountain West (RR, 0.82).
Among those aged 35-49 years at diagnosis, researchers found three hot spots – two in the Southeast (RR,1.20 and 1.16) and in the Great Lakes region (RR, 1.12). Several cold spots emerged from the mortality data on young-onset CRC in this age group – in the Pacific/Mountain West (RR, 0.90), in California (RR, 0.82), southern Texas (RR, 0.89), and the Southwest more broadly (RR, 0.86).
“Though cold spots were similar across strata, young-onset CRC hot spots shifted southward in the 35-49 age stratum in comparison to the less than 35 group,” the team notes.
They acknowledge several limitations to the study, including its “ecological nature” and the lack of adjustment for stage at diagnosis.
In comments to this news organization, Andrew T. Chan, MD, MPH, of Massachusetts General Hospital and Harvard Medical School, Boston, said the approach used by the researchers was “very interesting.”
Dr. Chan said that this is “one of the first studies that has given us insight into whether there is potential geographic variation in the incidence of young-onset colorectal cancer.”
This, he continued, is “very helpful in terms of thinking about potential risk factors for early-onset cancer and giving us more information about where we might want to focus our efforts in terms of prevention.”
Dr. Chan added that another interesting aspect of the study was that “the patterns might be different, depending on how you define early-onset cancer,” whether as “very-early onset,” defined as onset in those younger than 35, or the “less stringent definition” of 35-49 years.
He said that, “within the group that we’re calling very-early onset, there may be enriched factors,” compared with people who are “a little bit older.”
The research was supported by a National Cancer Institute of the National Institutes of Health grant to Case Comprehensive Cancer Center. Dr. Schmit reports no relevant financial relationships. Other authors have relationships with Exelixis, Tempus, Olympus, Anthos, Bayer, BMS, Janssen, Nektar Therapeutics, Pfizer, Sanofi, and WebMD/Medscape. Dr. Chan reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM GASTROENTEROLOGY
Quicker remission with tofacitinib versus vedolizumab in ulcerative colitis: study
When anti–tumor necrosis factor-alpha (anti-TNF) treatment fails to achieve remission for patients with ulcerative colitis (UC), tofacitinib (Xeljanz) appears more effect sooner than vedolizumab (Entyvio), suggests a Dutch registry study.
Data on nearly 150 patients with UC who had already undergone treatment with anti-TNF drugs showed that combined clinical and biochemical remission was about five times more likely with tofacitinib versus vedolizumab within 12 weeks of starting therapy.
However, the differences tailed off over subsequent weeks, such that there was no significant difference in combined remission rates at 52 weeks. There were also no notable differences in safety between the two drugs.
“These results may help in guiding clinical decisionmaking after anti-TNF failure in patients with UC,” the authors write.
The research was published online by Clinical Gastroenterology and Hepatology.
Real-world evidence
“This study offers more real-world evidence than a standard randomized controlled trial, since there was no randomization between the two study groups and no strict inclusion and exclusion criteria,” co–senior authors Tessa Straatmijer, MD, PhD candidate, and Marjolijn Duijvestein, MD, Amsterdam University Medical Center, the Netherlands, told this news organization.
They continued: “It is known that tofacitinib is more rapid of action compared to vedolizumab. We therefore expected that the odds ratio of remission rates between the two groups would be higher at weeks 12 and 24, compared to week 52.”
“We will continue with collecting data in our prospective cohort up to 10 years after initiating tofacitinib or vedolizumab,” Dr. Straatmijer and Dr. Duijvestein added. “Hopefully we can provide long-term outcomes after a couple of years.”
The authors highlight that for a “considerable proportion” of patients with UC, their condition does not respond to anti-TNF drugs, they experience adverse effects, or the response diminishes over time. Alternatives, such as vedolizumab and tofacitinib, are typically “prescribed after failure of the anti-TNF,” owing to their price and clinician experience.
While vedolizumab (an α4β7 integrin blocker) and tofacitinib (a Janus kinase inhibitor) have different mechanisms of action, head-to-head randomized controlled trials comparing their efficacy among patients with UC whose condition is refractory to anti-TNF are “lacking,” they add. “However, to guide physician decisionmaking on the most suitable drug choice after anti-TNF failure, effectiveness data comparing tofacitinib with vedolizumab is pivotal.”
To assess the comparative effectiveness and safety of the next therapeutic options, the team examined data from the Dutch Initiative on Crohn and Colitis registry.
They identified nearly 300 adult patients with clinical or biochemical disease activity who had initiated treatment with vedolizumab or tofacitinib. They excluded patients without prior anti-TNF treatment, those who had previously been treated with vedolizumab or tofacitinib, and those who did not have clinical and biochemical or endoscopic disease activity at baseline. The final analysis included 83 patients given vedolizumab and 65 treated with tofacitinib.
Patients given tofacitinib received 10 mg twice daily for the first 8 weeks, followed by maintenance treatment of 5 mg twice daily, with optional dose optimization in case of insufficient response. Vedolizumab was administered intravenously in line with the label; 300 mg was administered at weeks 0, 2, and 6, followed by 300 mg every 8 weeks, with a shortened infusion interval in cases of inadequate response.
There were few differences between the two groups at baseline, although patients given vedolizumab had been treated longer than those in the tofacitinib group (12 years vs. 7 years). Vedolizumab patients were also more likely to be receiving concomitant oral prednisone at baseline (50.6% vs. 30.8%).
Early difference fades
Corticosteroid-free clinical remission at week 12 was observed in 27.7% of patients in the vedolizumab group, rising to 38.6% at week 24 and 37.3% at week 52. Among those given tofacitinib, the rates of clinical remission were 56.9% at week 12, 60.0% at week 24, and 55.4% at week 52.
Propensity score-weight analysis revealed that tofacitinib patients were more likely to achieve corticosteroid-free clinical remission at weeks 12, 24, and 52, compared with those given vedolizumab, at odds ratio of 6.33, 3.02, and 1.86, respectively.
Biochemical remission rates among patients treated with vedolizumab were 25.3% at week 12, 28.9% at week 24, and 22.9% at week 52. For the tofacitinib group, the rates were 40.0%, 36.9%, and 27.7%, respectively. Biochemical remission was defined by C-reactive protein or fecal calprotectin levels.
The likelihood of biochemical remission was again greater with tofacitinib than with vedolizumab, at an odds ratio of 3.27 at week 12, 1.87 at week 24, and 1.81 at week 52.
Combined clinical and biochemical remission was more likely among patients given tofacitinib versus vedolizumab at week 12, at an odds ratio of 5.05, and at week 24, at an odds ratio of 2.11. However, at week 52, the difference was no longer significant, at an odds ratio of 1.17.
The authors note that there was no difference in the rate of infection between the two treatment groups, and the rate of severe adverse events was similar. However, three patients receiving tofacitinib experienced herpes simplex infections, compared with none of those given vedolizumab.
But, compared with the tofacitinib group, patients taking vedolizumab were more likely to discontinue treatment before 52 weeks, primarily because of a lack of response to treatment.
“The present study underlines that both vedolizumab and tofacitinib are relatively safe treatment options in patients with UC in a 12-month period,” the team writes.
‘Interesting’ efficacy data
Approached for comment, Alan C. Moss, MD, a professor of gastroenterology at Boston University School of Medicine, said that the findings are “interesting” for clinicians.
“We have so many treatment options right now, picking one over the other, particularly in patients like this who fail anti-TNF, is very important,” he told this news organization.
While he noted that registry data such as these are usually powered for “one outcome” (either efficacy or safety), “the immediate conclusions that come to mind are that certainly the efficacy of the two drugs in this patient population looks impressive.
“What we do note, though, is over time, as you get longer into the study, they start to become closer in terms of overall remission,” which Dr. Moss said fits with the current understanding that vedolizumab “takes longer to work.”
The take-away lesson from the study is that the short-term efficacy of tofacitinib is “superior,” Dr. Moss said, but, over the medium to long term, vedolizumab “may turn out to be more equivalent.”
Dr. Moss also pointed out that approximately 40% of patients given tofacitinib in the study began with the higher 10-mg twice-daily dose, “which is not the FDA-approved maintenance dose,” and over time about a quarter stayed on the higher dose.
“What that tells us is that, yes, it works faster if you’re using the higher dose, and over time, a certain proportion of these patients needed a higher dose to get these results,” he said.
Consequently, Dr. Moss said that the two treatment groups were not “equivalent” in terms of the doses given relative to normal maintenance dose.
The Initiative on Crohn and Colitis Fellowship is sponsored by AbbVie, Pfizer, Takeda, Celgene, Janssen Pharmaceutica, Teva Pharmaceutical Industries, Cablon Medical, Ferring Pharmaceuticals, Mundipharma, Dr. Falk Pharma, Sandoz, and Tramedico. Dr. Duijvestein has relationships with Echo Pharma, Robarts Clinical Trials, Janssen, Merck, Pfizer, Takeda, Tillotts Pharma, and Dr. Falk Pharma. Other authors have numerous relationships with industry. Dr. Moss has relationships with Pfizer and Janssen.
A version of this article first appeared on Medscape.com.
When anti–tumor necrosis factor-alpha (anti-TNF) treatment fails to achieve remission for patients with ulcerative colitis (UC), tofacitinib (Xeljanz) appears more effect sooner than vedolizumab (Entyvio), suggests a Dutch registry study.
Data on nearly 150 patients with UC who had already undergone treatment with anti-TNF drugs showed that combined clinical and biochemical remission was about five times more likely with tofacitinib versus vedolizumab within 12 weeks of starting therapy.
However, the differences tailed off over subsequent weeks, such that there was no significant difference in combined remission rates at 52 weeks. There were also no notable differences in safety between the two drugs.
“These results may help in guiding clinical decisionmaking after anti-TNF failure in patients with UC,” the authors write.
The research was published online by Clinical Gastroenterology and Hepatology.
Real-world evidence
“This study offers more real-world evidence than a standard randomized controlled trial, since there was no randomization between the two study groups and no strict inclusion and exclusion criteria,” co–senior authors Tessa Straatmijer, MD, PhD candidate, and Marjolijn Duijvestein, MD, Amsterdam University Medical Center, the Netherlands, told this news organization.
They continued: “It is known that tofacitinib is more rapid of action compared to vedolizumab. We therefore expected that the odds ratio of remission rates between the two groups would be higher at weeks 12 and 24, compared to week 52.”
“We will continue with collecting data in our prospective cohort up to 10 years after initiating tofacitinib or vedolizumab,” Dr. Straatmijer and Dr. Duijvestein added. “Hopefully we can provide long-term outcomes after a couple of years.”
The authors highlight that for a “considerable proportion” of patients with UC, their condition does not respond to anti-TNF drugs, they experience adverse effects, or the response diminishes over time. Alternatives, such as vedolizumab and tofacitinib, are typically “prescribed after failure of the anti-TNF,” owing to their price and clinician experience.
While vedolizumab (an α4β7 integrin blocker) and tofacitinib (a Janus kinase inhibitor) have different mechanisms of action, head-to-head randomized controlled trials comparing their efficacy among patients with UC whose condition is refractory to anti-TNF are “lacking,” they add. “However, to guide physician decisionmaking on the most suitable drug choice after anti-TNF failure, effectiveness data comparing tofacitinib with vedolizumab is pivotal.”
To assess the comparative effectiveness and safety of the next therapeutic options, the team examined data from the Dutch Initiative on Crohn and Colitis registry.
They identified nearly 300 adult patients with clinical or biochemical disease activity who had initiated treatment with vedolizumab or tofacitinib. They excluded patients without prior anti-TNF treatment, those who had previously been treated with vedolizumab or tofacitinib, and those who did not have clinical and biochemical or endoscopic disease activity at baseline. The final analysis included 83 patients given vedolizumab and 65 treated with tofacitinib.
Patients given tofacitinib received 10 mg twice daily for the first 8 weeks, followed by maintenance treatment of 5 mg twice daily, with optional dose optimization in case of insufficient response. Vedolizumab was administered intravenously in line with the label; 300 mg was administered at weeks 0, 2, and 6, followed by 300 mg every 8 weeks, with a shortened infusion interval in cases of inadequate response.
There were few differences between the two groups at baseline, although patients given vedolizumab had been treated longer than those in the tofacitinib group (12 years vs. 7 years). Vedolizumab patients were also more likely to be receiving concomitant oral prednisone at baseline (50.6% vs. 30.8%).
Early difference fades
Corticosteroid-free clinical remission at week 12 was observed in 27.7% of patients in the vedolizumab group, rising to 38.6% at week 24 and 37.3% at week 52. Among those given tofacitinib, the rates of clinical remission were 56.9% at week 12, 60.0% at week 24, and 55.4% at week 52.
Propensity score-weight analysis revealed that tofacitinib patients were more likely to achieve corticosteroid-free clinical remission at weeks 12, 24, and 52, compared with those given vedolizumab, at odds ratio of 6.33, 3.02, and 1.86, respectively.
Biochemical remission rates among patients treated with vedolizumab were 25.3% at week 12, 28.9% at week 24, and 22.9% at week 52. For the tofacitinib group, the rates were 40.0%, 36.9%, and 27.7%, respectively. Biochemical remission was defined by C-reactive protein or fecal calprotectin levels.
The likelihood of biochemical remission was again greater with tofacitinib than with vedolizumab, at an odds ratio of 3.27 at week 12, 1.87 at week 24, and 1.81 at week 52.
Combined clinical and biochemical remission was more likely among patients given tofacitinib versus vedolizumab at week 12, at an odds ratio of 5.05, and at week 24, at an odds ratio of 2.11. However, at week 52, the difference was no longer significant, at an odds ratio of 1.17.
The authors note that there was no difference in the rate of infection between the two treatment groups, and the rate of severe adverse events was similar. However, three patients receiving tofacitinib experienced herpes simplex infections, compared with none of those given vedolizumab.
But, compared with the tofacitinib group, patients taking vedolizumab were more likely to discontinue treatment before 52 weeks, primarily because of a lack of response to treatment.
“The present study underlines that both vedolizumab and tofacitinib are relatively safe treatment options in patients with UC in a 12-month period,” the team writes.
‘Interesting’ efficacy data
Approached for comment, Alan C. Moss, MD, a professor of gastroenterology at Boston University School of Medicine, said that the findings are “interesting” for clinicians.
“We have so many treatment options right now, picking one over the other, particularly in patients like this who fail anti-TNF, is very important,” he told this news organization.
While he noted that registry data such as these are usually powered for “one outcome” (either efficacy or safety), “the immediate conclusions that come to mind are that certainly the efficacy of the two drugs in this patient population looks impressive.
“What we do note, though, is over time, as you get longer into the study, they start to become closer in terms of overall remission,” which Dr. Moss said fits with the current understanding that vedolizumab “takes longer to work.”
The take-away lesson from the study is that the short-term efficacy of tofacitinib is “superior,” Dr. Moss said, but, over the medium to long term, vedolizumab “may turn out to be more equivalent.”
Dr. Moss also pointed out that approximately 40% of patients given tofacitinib in the study began with the higher 10-mg twice-daily dose, “which is not the FDA-approved maintenance dose,” and over time about a quarter stayed on the higher dose.
“What that tells us is that, yes, it works faster if you’re using the higher dose, and over time, a certain proportion of these patients needed a higher dose to get these results,” he said.
Consequently, Dr. Moss said that the two treatment groups were not “equivalent” in terms of the doses given relative to normal maintenance dose.
The Initiative on Crohn and Colitis Fellowship is sponsored by AbbVie, Pfizer, Takeda, Celgene, Janssen Pharmaceutica, Teva Pharmaceutical Industries, Cablon Medical, Ferring Pharmaceuticals, Mundipharma, Dr. Falk Pharma, Sandoz, and Tramedico. Dr. Duijvestein has relationships with Echo Pharma, Robarts Clinical Trials, Janssen, Merck, Pfizer, Takeda, Tillotts Pharma, and Dr. Falk Pharma. Other authors have numerous relationships with industry. Dr. Moss has relationships with Pfizer and Janssen.
A version of this article first appeared on Medscape.com.
When anti–tumor necrosis factor-alpha (anti-TNF) treatment fails to achieve remission for patients with ulcerative colitis (UC), tofacitinib (Xeljanz) appears more effect sooner than vedolizumab (Entyvio), suggests a Dutch registry study.
Data on nearly 150 patients with UC who had already undergone treatment with anti-TNF drugs showed that combined clinical and biochemical remission was about five times more likely with tofacitinib versus vedolizumab within 12 weeks of starting therapy.
However, the differences tailed off over subsequent weeks, such that there was no significant difference in combined remission rates at 52 weeks. There were also no notable differences in safety between the two drugs.
“These results may help in guiding clinical decisionmaking after anti-TNF failure in patients with UC,” the authors write.
The research was published online by Clinical Gastroenterology and Hepatology.
Real-world evidence
“This study offers more real-world evidence than a standard randomized controlled trial, since there was no randomization between the two study groups and no strict inclusion and exclusion criteria,” co–senior authors Tessa Straatmijer, MD, PhD candidate, and Marjolijn Duijvestein, MD, Amsterdam University Medical Center, the Netherlands, told this news organization.
They continued: “It is known that tofacitinib is more rapid of action compared to vedolizumab. We therefore expected that the odds ratio of remission rates between the two groups would be higher at weeks 12 and 24, compared to week 52.”
“We will continue with collecting data in our prospective cohort up to 10 years after initiating tofacitinib or vedolizumab,” Dr. Straatmijer and Dr. Duijvestein added. “Hopefully we can provide long-term outcomes after a couple of years.”
The authors highlight that for a “considerable proportion” of patients with UC, their condition does not respond to anti-TNF drugs, they experience adverse effects, or the response diminishes over time. Alternatives, such as vedolizumab and tofacitinib, are typically “prescribed after failure of the anti-TNF,” owing to their price and clinician experience.
While vedolizumab (an α4β7 integrin blocker) and tofacitinib (a Janus kinase inhibitor) have different mechanisms of action, head-to-head randomized controlled trials comparing their efficacy among patients with UC whose condition is refractory to anti-TNF are “lacking,” they add. “However, to guide physician decisionmaking on the most suitable drug choice after anti-TNF failure, effectiveness data comparing tofacitinib with vedolizumab is pivotal.”
To assess the comparative effectiveness and safety of the next therapeutic options, the team examined data from the Dutch Initiative on Crohn and Colitis registry.
They identified nearly 300 adult patients with clinical or biochemical disease activity who had initiated treatment with vedolizumab or tofacitinib. They excluded patients without prior anti-TNF treatment, those who had previously been treated with vedolizumab or tofacitinib, and those who did not have clinical and biochemical or endoscopic disease activity at baseline. The final analysis included 83 patients given vedolizumab and 65 treated with tofacitinib.
Patients given tofacitinib received 10 mg twice daily for the first 8 weeks, followed by maintenance treatment of 5 mg twice daily, with optional dose optimization in case of insufficient response. Vedolizumab was administered intravenously in line with the label; 300 mg was administered at weeks 0, 2, and 6, followed by 300 mg every 8 weeks, with a shortened infusion interval in cases of inadequate response.
There were few differences between the two groups at baseline, although patients given vedolizumab had been treated longer than those in the tofacitinib group (12 years vs. 7 years). Vedolizumab patients were also more likely to be receiving concomitant oral prednisone at baseline (50.6% vs. 30.8%).
Early difference fades
Corticosteroid-free clinical remission at week 12 was observed in 27.7% of patients in the vedolizumab group, rising to 38.6% at week 24 and 37.3% at week 52. Among those given tofacitinib, the rates of clinical remission were 56.9% at week 12, 60.0% at week 24, and 55.4% at week 52.
Propensity score-weight analysis revealed that tofacitinib patients were more likely to achieve corticosteroid-free clinical remission at weeks 12, 24, and 52, compared with those given vedolizumab, at odds ratio of 6.33, 3.02, and 1.86, respectively.
Biochemical remission rates among patients treated with vedolizumab were 25.3% at week 12, 28.9% at week 24, and 22.9% at week 52. For the tofacitinib group, the rates were 40.0%, 36.9%, and 27.7%, respectively. Biochemical remission was defined by C-reactive protein or fecal calprotectin levels.
The likelihood of biochemical remission was again greater with tofacitinib than with vedolizumab, at an odds ratio of 3.27 at week 12, 1.87 at week 24, and 1.81 at week 52.
Combined clinical and biochemical remission was more likely among patients given tofacitinib versus vedolizumab at week 12, at an odds ratio of 5.05, and at week 24, at an odds ratio of 2.11. However, at week 52, the difference was no longer significant, at an odds ratio of 1.17.
The authors note that there was no difference in the rate of infection between the two treatment groups, and the rate of severe adverse events was similar. However, three patients receiving tofacitinib experienced herpes simplex infections, compared with none of those given vedolizumab.
But, compared with the tofacitinib group, patients taking vedolizumab were more likely to discontinue treatment before 52 weeks, primarily because of a lack of response to treatment.
“The present study underlines that both vedolizumab and tofacitinib are relatively safe treatment options in patients with UC in a 12-month period,” the team writes.
‘Interesting’ efficacy data
Approached for comment, Alan C. Moss, MD, a professor of gastroenterology at Boston University School of Medicine, said that the findings are “interesting” for clinicians.
“We have so many treatment options right now, picking one over the other, particularly in patients like this who fail anti-TNF, is very important,” he told this news organization.
While he noted that registry data such as these are usually powered for “one outcome” (either efficacy or safety), “the immediate conclusions that come to mind are that certainly the efficacy of the two drugs in this patient population looks impressive.
“What we do note, though, is over time, as you get longer into the study, they start to become closer in terms of overall remission,” which Dr. Moss said fits with the current understanding that vedolizumab “takes longer to work.”
The take-away lesson from the study is that the short-term efficacy of tofacitinib is “superior,” Dr. Moss said, but, over the medium to long term, vedolizumab “may turn out to be more equivalent.”
Dr. Moss also pointed out that approximately 40% of patients given tofacitinib in the study began with the higher 10-mg twice-daily dose, “which is not the FDA-approved maintenance dose,” and over time about a quarter stayed on the higher dose.
“What that tells us is that, yes, it works faster if you’re using the higher dose, and over time, a certain proportion of these patients needed a higher dose to get these results,” he said.
Consequently, Dr. Moss said that the two treatment groups were not “equivalent” in terms of the doses given relative to normal maintenance dose.
The Initiative on Crohn and Colitis Fellowship is sponsored by AbbVie, Pfizer, Takeda, Celgene, Janssen Pharmaceutica, Teva Pharmaceutical Industries, Cablon Medical, Ferring Pharmaceuticals, Mundipharma, Dr. Falk Pharma, Sandoz, and Tramedico. Dr. Duijvestein has relationships with Echo Pharma, Robarts Clinical Trials, Janssen, Merck, Pfizer, Takeda, Tillotts Pharma, and Dr. Falk Pharma. Other authors have numerous relationships with industry. Dr. Moss has relationships with Pfizer and Janssen.
A version of this article first appeared on Medscape.com.