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Sex-triggered sudden cardiac arrest extremely rare
ANAHEIM, CALIF. – Patients with heart disease can safely be reassured that sexual intercourse as a trigger for sudden cardiac death is extremely rare, Aapo Aro, MD, said at the American Heart Association scientific sessions.
He presented an analysis from the ongoing Oregon Sudden Unexpected Death Study, a population-based case-control study that captures all cases of sudden cardiac arrest (SCA) in the Portland, Ore., area.
This was the first-ever study to examine the burden of SCA triggered by sexual activity. Of 4,557 adjudicated cases of SCA in adults during 2002-2015, a mere 34, or 0.7%, happened during or within 1 hour of sexual intercourse.
Thirty-two of the 34 cases occurred in men. That works out to 1% of SCAs in men being related to sexual activity. In women, the rate was 10-fold lower, at 0.1%, noted Dr. Aro, a cardiologist at Helsinki University Hospital who was at Cedars-Sinai Medical Center in Los Angeles at the time he conducted this research.
Many of the Oregonians who experienced SCA had known heart disease at the time, regardless of whether the event occurred during sexual activity or at another time. Of note, however, SCA during sexual activity presented with ventricular fibrillation/ventricular tachycardia in 76% of cases, versus a 45% rate in individuals whose SCA was not associated with sexual intercourse.
“The data are very reassuring,” Dr. Aro said in an interview. “Many of these patients had known cardiac disease, but still the absolute numbers of events are very small. Our take home message from this study is that sexual activity can be regarded as safe even in cardiac patients.”
The Oregon Sudden Unexpected Death Study is funded by the National Heart, Lung, and Blood Institute and the American Heart Association. Dr. Aro reported having no financial conflicts of interest.
ANAHEIM, CALIF. – Patients with heart disease can safely be reassured that sexual intercourse as a trigger for sudden cardiac death is extremely rare, Aapo Aro, MD, said at the American Heart Association scientific sessions.
He presented an analysis from the ongoing Oregon Sudden Unexpected Death Study, a population-based case-control study that captures all cases of sudden cardiac arrest (SCA) in the Portland, Ore., area.
This was the first-ever study to examine the burden of SCA triggered by sexual activity. Of 4,557 adjudicated cases of SCA in adults during 2002-2015, a mere 34, or 0.7%, happened during or within 1 hour of sexual intercourse.
Thirty-two of the 34 cases occurred in men. That works out to 1% of SCAs in men being related to sexual activity. In women, the rate was 10-fold lower, at 0.1%, noted Dr. Aro, a cardiologist at Helsinki University Hospital who was at Cedars-Sinai Medical Center in Los Angeles at the time he conducted this research.
Many of the Oregonians who experienced SCA had known heart disease at the time, regardless of whether the event occurred during sexual activity or at another time. Of note, however, SCA during sexual activity presented with ventricular fibrillation/ventricular tachycardia in 76% of cases, versus a 45% rate in individuals whose SCA was not associated with sexual intercourse.
“The data are very reassuring,” Dr. Aro said in an interview. “Many of these patients had known cardiac disease, but still the absolute numbers of events are very small. Our take home message from this study is that sexual activity can be regarded as safe even in cardiac patients.”
The Oregon Sudden Unexpected Death Study is funded by the National Heart, Lung, and Blood Institute and the American Heart Association. Dr. Aro reported having no financial conflicts of interest.
ANAHEIM, CALIF. – Patients with heart disease can safely be reassured that sexual intercourse as a trigger for sudden cardiac death is extremely rare, Aapo Aro, MD, said at the American Heart Association scientific sessions.
He presented an analysis from the ongoing Oregon Sudden Unexpected Death Study, a population-based case-control study that captures all cases of sudden cardiac arrest (SCA) in the Portland, Ore., area.
This was the first-ever study to examine the burden of SCA triggered by sexual activity. Of 4,557 adjudicated cases of SCA in adults during 2002-2015, a mere 34, or 0.7%, happened during or within 1 hour of sexual intercourse.
Thirty-two of the 34 cases occurred in men. That works out to 1% of SCAs in men being related to sexual activity. In women, the rate was 10-fold lower, at 0.1%, noted Dr. Aro, a cardiologist at Helsinki University Hospital who was at Cedars-Sinai Medical Center in Los Angeles at the time he conducted this research.
Many of the Oregonians who experienced SCA had known heart disease at the time, regardless of whether the event occurred during sexual activity or at another time. Of note, however, SCA during sexual activity presented with ventricular fibrillation/ventricular tachycardia in 76% of cases, versus a 45% rate in individuals whose SCA was not associated with sexual intercourse.
“The data are very reassuring,” Dr. Aro said in an interview. “Many of these patients had known cardiac disease, but still the absolute numbers of events are very small. Our take home message from this study is that sexual activity can be regarded as safe even in cardiac patients.”
The Oregon Sudden Unexpected Death Study is funded by the National Heart, Lung, and Blood Institute and the American Heart Association. Dr. Aro reported having no financial conflicts of interest.
REPORTING FROM THE AHA SCIENTIFIC SESSIONS
Key clinical point: Patients with cardiac disease needn’t shy away from sexual intercourse because it might trigger cardiac arrest.
Major finding: Only 0.7% of 4,557 adjudicated sudden cardiac arrests occurred in association with sexual intercourse.
Study details: This population-based case-control study examined 4,557 sudden cardiac arrests in the Portland, Ore., area.
Disclosures: The Oregon Sudden Unexpected Death Study is funded by the National Heart, Lung and Blood Institute and American Heart Association. The presenter reported having no financial conflicts.
Phase 3 trials show halobetasol/tazarotene lotion works for psoriasis
KAUAI, HAWAII – in two phase 3 randomized, double-blind, multicenter clinical trials, Linda Stein Gold, MD, reported at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.
The fixed combination of halobetasol 0.01%/tazarotene 0.045% lotion takes advantage of an observation made 20 years ago: When tazarotene is combined with a potent topical corticosteroid, therapeutic efficacy is amplified synergistically while the problematic local side effects of each agent are diminished, explained Dr. Stein Gold, director of dermatology research at the Henry Ford Health System, Detroit.
“Tazarotene: Great for acne, but think of it again for psoriasis,” Dr. Stein Gold said. “It makes sense. Tazarotene improves differentiation of the skin; it decreases inflammation; it decreases proliferation – it does all the good things that we want to do for psoriasis.
“It’s got a little bit of baggage, though,” she continued. “It’s pregnancy Category X, so you have to make sure a woman who is or may become pregnant is not using it. And there are some side effects. It can be tough to use. When you use it in psoriasis you can get local irritation up to 30% of the time.”
The two parallel phase 3 randomized trials plus a separate phase 2 study, all of which Dr. Stein Gold was involved in, showed that the efficacy of the investigational halobetasol/tazarotene fixed combination was greater than either component alone, side effects were minimized, and efficacy remained durable 4 weeks after the 8-week treatment course ended.
The not-yet-published phase 3 trials included 418 patients with moderate to severe psoriasis randomized 2:1 to once-daily application of halobetasol/tazarotene or its vehicle for 8 weeks. Treatment success, defined as at least a two-grade improvement from baseline in Investigator’s Global Assessment score plus a score of clear or almost clear, was documented at 8 weeks in 35.8% of the halobetasol/tazarotene group in one study and 45.3% in the other, compared with 7% and 12.5% of controls, respectively.
In addition, after 8 weeks, affected body surface area was reduced by a mean of 32.8% in one study and by 42.5% in the other. There was also at least a two-grade improvement in plaque erythema at the target lesion site in 42.2% and 49.6% of halobetasol/tazarotene–treated patients in the two trials. A two-grade improvement in plaque elevation was noted in 59.3% and 59.7% of patients, while for plaque scaling, the figures were 59.4% and 62.9%.
“What we found in the two sister studies was statistically significant success in getting those plaques from moderate/severe all the way down to clear/almost clear,” Dr. Stein Gold said.
The most frequently reported treatment-emergent adverse events included contact dermatitis in 7.4% of the active treatment group and application site pain in 2.6%. Most side effects were mild or moderate in nature.
The phase 2 study, which included 212 psoriasis patients, looked specifically at maintenance of efficacy after end of treatment. Here, halobetasol/tazarotene showed durability of therapeutic benefit: 4 weeks after completing the 8-week course of once-daily halobetasol/tazarotene, 38.2% of patients still met the criteria for treatment success. The minimal skin atrophy that arose during treatment largely resolved during the subsequent 4 weeks off treatment.
The clinical trials were supported by Valeant. Dr. Stein Gold reported receiving research grants from and serving as a consultant to, paid speaker for, and scientific advisory board member for Valeant and numerous other pharmaceutical companies active in dermatologic drug development.
SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
KAUAI, HAWAII – in two phase 3 randomized, double-blind, multicenter clinical trials, Linda Stein Gold, MD, reported at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.
The fixed combination of halobetasol 0.01%/tazarotene 0.045% lotion takes advantage of an observation made 20 years ago: When tazarotene is combined with a potent topical corticosteroid, therapeutic efficacy is amplified synergistically while the problematic local side effects of each agent are diminished, explained Dr. Stein Gold, director of dermatology research at the Henry Ford Health System, Detroit.
“Tazarotene: Great for acne, but think of it again for psoriasis,” Dr. Stein Gold said. “It makes sense. Tazarotene improves differentiation of the skin; it decreases inflammation; it decreases proliferation – it does all the good things that we want to do for psoriasis.
“It’s got a little bit of baggage, though,” she continued. “It’s pregnancy Category X, so you have to make sure a woman who is or may become pregnant is not using it. And there are some side effects. It can be tough to use. When you use it in psoriasis you can get local irritation up to 30% of the time.”
The two parallel phase 3 randomized trials plus a separate phase 2 study, all of which Dr. Stein Gold was involved in, showed that the efficacy of the investigational halobetasol/tazarotene fixed combination was greater than either component alone, side effects were minimized, and efficacy remained durable 4 weeks after the 8-week treatment course ended.
The not-yet-published phase 3 trials included 418 patients with moderate to severe psoriasis randomized 2:1 to once-daily application of halobetasol/tazarotene or its vehicle for 8 weeks. Treatment success, defined as at least a two-grade improvement from baseline in Investigator’s Global Assessment score plus a score of clear or almost clear, was documented at 8 weeks in 35.8% of the halobetasol/tazarotene group in one study and 45.3% in the other, compared with 7% and 12.5% of controls, respectively.
In addition, after 8 weeks, affected body surface area was reduced by a mean of 32.8% in one study and by 42.5% in the other. There was also at least a two-grade improvement in plaque erythema at the target lesion site in 42.2% and 49.6% of halobetasol/tazarotene–treated patients in the two trials. A two-grade improvement in plaque elevation was noted in 59.3% and 59.7% of patients, while for plaque scaling, the figures were 59.4% and 62.9%.
“What we found in the two sister studies was statistically significant success in getting those plaques from moderate/severe all the way down to clear/almost clear,” Dr. Stein Gold said.
The most frequently reported treatment-emergent adverse events included contact dermatitis in 7.4% of the active treatment group and application site pain in 2.6%. Most side effects were mild or moderate in nature.
The phase 2 study, which included 212 psoriasis patients, looked specifically at maintenance of efficacy after end of treatment. Here, halobetasol/tazarotene showed durability of therapeutic benefit: 4 weeks after completing the 8-week course of once-daily halobetasol/tazarotene, 38.2% of patients still met the criteria for treatment success. The minimal skin atrophy that arose during treatment largely resolved during the subsequent 4 weeks off treatment.
The clinical trials were supported by Valeant. Dr. Stein Gold reported receiving research grants from and serving as a consultant to, paid speaker for, and scientific advisory board member for Valeant and numerous other pharmaceutical companies active in dermatologic drug development.
SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
KAUAI, HAWAII – in two phase 3 randomized, double-blind, multicenter clinical trials, Linda Stein Gold, MD, reported at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.
The fixed combination of halobetasol 0.01%/tazarotene 0.045% lotion takes advantage of an observation made 20 years ago: When tazarotene is combined with a potent topical corticosteroid, therapeutic efficacy is amplified synergistically while the problematic local side effects of each agent are diminished, explained Dr. Stein Gold, director of dermatology research at the Henry Ford Health System, Detroit.
“Tazarotene: Great for acne, but think of it again for psoriasis,” Dr. Stein Gold said. “It makes sense. Tazarotene improves differentiation of the skin; it decreases inflammation; it decreases proliferation – it does all the good things that we want to do for psoriasis.
“It’s got a little bit of baggage, though,” she continued. “It’s pregnancy Category X, so you have to make sure a woman who is or may become pregnant is not using it. And there are some side effects. It can be tough to use. When you use it in psoriasis you can get local irritation up to 30% of the time.”
The two parallel phase 3 randomized trials plus a separate phase 2 study, all of which Dr. Stein Gold was involved in, showed that the efficacy of the investigational halobetasol/tazarotene fixed combination was greater than either component alone, side effects were minimized, and efficacy remained durable 4 weeks after the 8-week treatment course ended.
The not-yet-published phase 3 trials included 418 patients with moderate to severe psoriasis randomized 2:1 to once-daily application of halobetasol/tazarotene or its vehicle for 8 weeks. Treatment success, defined as at least a two-grade improvement from baseline in Investigator’s Global Assessment score plus a score of clear or almost clear, was documented at 8 weeks in 35.8% of the halobetasol/tazarotene group in one study and 45.3% in the other, compared with 7% and 12.5% of controls, respectively.
In addition, after 8 weeks, affected body surface area was reduced by a mean of 32.8% in one study and by 42.5% in the other. There was also at least a two-grade improvement in plaque erythema at the target lesion site in 42.2% and 49.6% of halobetasol/tazarotene–treated patients in the two trials. A two-grade improvement in plaque elevation was noted in 59.3% and 59.7% of patients, while for plaque scaling, the figures were 59.4% and 62.9%.
“What we found in the two sister studies was statistically significant success in getting those plaques from moderate/severe all the way down to clear/almost clear,” Dr. Stein Gold said.
The most frequently reported treatment-emergent adverse events included contact dermatitis in 7.4% of the active treatment group and application site pain in 2.6%. Most side effects were mild or moderate in nature.
The phase 2 study, which included 212 psoriasis patients, looked specifically at maintenance of efficacy after end of treatment. Here, halobetasol/tazarotene showed durability of therapeutic benefit: 4 weeks after completing the 8-week course of once-daily halobetasol/tazarotene, 38.2% of patients still met the criteria for treatment success. The minimal skin atrophy that arose during treatment largely resolved during the subsequent 4 weeks off treatment.
The clinical trials were supported by Valeant. Dr. Stein Gold reported receiving research grants from and serving as a consultant to, paid speaker for, and scientific advisory board member for Valeant and numerous other pharmaceutical companies active in dermatologic drug development.
SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
EXPERT ANALYSIS FROM SDEF HAWAII DERMATOLOGY SEMINAR
March 2018: Click for Credit
Here are 4 articles in the March issue of Clinician Reviews (individual articles are valid for one year from date of publication—expiration dates below):
1. Prenatal Maternal Anxiety Linked to Hyperactivity in Offspring as Teenagers
To take the posttest, go to: http://bit.ly/2BLXsRs
Expires November 15, 2018
2. The Better Mammogram: Experts Explore Sensitivity of New Modalities
To take the posttest, go to: http://bit.ly/2nQaJii
Expires November 14, 2018
3. Large Database Analysis Suggests Safety of Bariatric Surgery in Seniors
To take the posttest, go to: http://bit.ly/2E3tcmJ
Expires November 14, 2018
4. Salivary Biomarker for Huntington Disease Identified
To take the posttest, go to: http://bit.ly/2BGQpJP
Expires November 13, 2018
Here are 4 articles in the March issue of Clinician Reviews (individual articles are valid for one year from date of publication—expiration dates below):
1. Prenatal Maternal Anxiety Linked to Hyperactivity in Offspring as Teenagers
To take the posttest, go to: http://bit.ly/2BLXsRs
Expires November 15, 2018
2. The Better Mammogram: Experts Explore Sensitivity of New Modalities
To take the posttest, go to: http://bit.ly/2nQaJii
Expires November 14, 2018
3. Large Database Analysis Suggests Safety of Bariatric Surgery in Seniors
To take the posttest, go to: http://bit.ly/2E3tcmJ
Expires November 14, 2018
4. Salivary Biomarker for Huntington Disease Identified
To take the posttest, go to: http://bit.ly/2BGQpJP
Expires November 13, 2018
Here are 4 articles in the March issue of Clinician Reviews (individual articles are valid for one year from date of publication—expiration dates below):
1. Prenatal Maternal Anxiety Linked to Hyperactivity in Offspring as Teenagers
To take the posttest, go to: http://bit.ly/2BLXsRs
Expires November 15, 2018
2. The Better Mammogram: Experts Explore Sensitivity of New Modalities
To take the posttest, go to: http://bit.ly/2nQaJii
Expires November 14, 2018
3. Large Database Analysis Suggests Safety of Bariatric Surgery in Seniors
To take the posttest, go to: http://bit.ly/2E3tcmJ
Expires November 14, 2018
4. Salivary Biomarker for Huntington Disease Identified
To take the posttest, go to: http://bit.ly/2BGQpJP
Expires November 13, 2018
Abruptio placenta brings increased cardiovascular risk – and soon
ANAHEIM, CALIF. – Women who experience placental abruption are at significantly increased risk for multiple forms of cardiovascular disease beginning within the first few years after their pregnancy complication, according to a study of more than 1.6 million California women.
While gestational hypertension, preeclampsia, and fetal growth restriction have previously all been shown to be associated with increased risk of incident cardiovascular disease, this huge California study provides the first strong epidemiologic evidence that placental abruption is as well. Prior studies looking at the issue have been underpowered, Michael J. Healey, MD, said at the American Heart Association scientific sessions.
“Our hypothesis is that there might be some type of shared mechanism, probably involving microvascular dysfunction, that explains the relationships we see between these pregnancy complications and increased near-term risk of cardiovascular disease,” he explained in an interview.
Dr. Healy, a hospitalist attached to the heart failure service at the University of California, San Francisco, presented a retrospective study of a multiethnic cohort comprising 1,614,950 parous women aged 15-50 years who participated in the California Healthcare Cost and Utility Project during 2005-2009. Placental abruption occurred in 15,057 of them at a mean age of 29.2 years.
During a median 4.9 years of follow-up, women who experienced abruptio placenta were at 6% increased risk for heart failure, 11% greater risk for MI, 8% increased risk for hypertensive urgency, and 2% greater risk for myocardial infarction with no obstructive atherosclerosis (MINOCA) in an age- and race-adjusted analysis. All of these were statistically significant differences.
Of note, however, in a multivariate analysis fully adjusted for standard cardiovascular risk factors, as well as hypercoagulability, preterm birth, grand multiparity, and insurance status, placental abruption was independently associated with a 2.14-fold risk of MINOCA, but it was no longer linked to significantly increased risks of the other cardiovascular events.
The implication is that the increased risk of these other forms of cardiovascular disease is mediated through the women’s increased prevalence of the traditional cardiovascular risk factors, whereas a novel mechanism – most likely microvascular dysfunction – underlies the association between placental abruption and MINOCA, according to Dr. Healy.
He plans to extend this research by taking a look at the relationship between placental abruption and the various subtypes of MINOCA, including coronary dissection, vasospasm, thrombophilia disorders, and stress cardiomyopathy, in order to examine whether the increased risk posed by placental abruption is concentrated in certain forms of MINOCA. Data on MINOCA subtypes were recorded as part of the California project.
He reported having no financial conflicts of interest regarding his study.
ANAHEIM, CALIF. – Women who experience placental abruption are at significantly increased risk for multiple forms of cardiovascular disease beginning within the first few years after their pregnancy complication, according to a study of more than 1.6 million California women.
While gestational hypertension, preeclampsia, and fetal growth restriction have previously all been shown to be associated with increased risk of incident cardiovascular disease, this huge California study provides the first strong epidemiologic evidence that placental abruption is as well. Prior studies looking at the issue have been underpowered, Michael J. Healey, MD, said at the American Heart Association scientific sessions.
“Our hypothesis is that there might be some type of shared mechanism, probably involving microvascular dysfunction, that explains the relationships we see between these pregnancy complications and increased near-term risk of cardiovascular disease,” he explained in an interview.
Dr. Healy, a hospitalist attached to the heart failure service at the University of California, San Francisco, presented a retrospective study of a multiethnic cohort comprising 1,614,950 parous women aged 15-50 years who participated in the California Healthcare Cost and Utility Project during 2005-2009. Placental abruption occurred in 15,057 of them at a mean age of 29.2 years.
During a median 4.9 years of follow-up, women who experienced abruptio placenta were at 6% increased risk for heart failure, 11% greater risk for MI, 8% increased risk for hypertensive urgency, and 2% greater risk for myocardial infarction with no obstructive atherosclerosis (MINOCA) in an age- and race-adjusted analysis. All of these were statistically significant differences.
Of note, however, in a multivariate analysis fully adjusted for standard cardiovascular risk factors, as well as hypercoagulability, preterm birth, grand multiparity, and insurance status, placental abruption was independently associated with a 2.14-fold risk of MINOCA, but it was no longer linked to significantly increased risks of the other cardiovascular events.
The implication is that the increased risk of these other forms of cardiovascular disease is mediated through the women’s increased prevalence of the traditional cardiovascular risk factors, whereas a novel mechanism – most likely microvascular dysfunction – underlies the association between placental abruption and MINOCA, according to Dr. Healy.
He plans to extend this research by taking a look at the relationship between placental abruption and the various subtypes of MINOCA, including coronary dissection, vasospasm, thrombophilia disorders, and stress cardiomyopathy, in order to examine whether the increased risk posed by placental abruption is concentrated in certain forms of MINOCA. Data on MINOCA subtypes were recorded as part of the California project.
He reported having no financial conflicts of interest regarding his study.
ANAHEIM, CALIF. – Women who experience placental abruption are at significantly increased risk for multiple forms of cardiovascular disease beginning within the first few years after their pregnancy complication, according to a study of more than 1.6 million California women.
While gestational hypertension, preeclampsia, and fetal growth restriction have previously all been shown to be associated with increased risk of incident cardiovascular disease, this huge California study provides the first strong epidemiologic evidence that placental abruption is as well. Prior studies looking at the issue have been underpowered, Michael J. Healey, MD, said at the American Heart Association scientific sessions.
“Our hypothesis is that there might be some type of shared mechanism, probably involving microvascular dysfunction, that explains the relationships we see between these pregnancy complications and increased near-term risk of cardiovascular disease,” he explained in an interview.
Dr. Healy, a hospitalist attached to the heart failure service at the University of California, San Francisco, presented a retrospective study of a multiethnic cohort comprising 1,614,950 parous women aged 15-50 years who participated in the California Healthcare Cost and Utility Project during 2005-2009. Placental abruption occurred in 15,057 of them at a mean age of 29.2 years.
During a median 4.9 years of follow-up, women who experienced abruptio placenta were at 6% increased risk for heart failure, 11% greater risk for MI, 8% increased risk for hypertensive urgency, and 2% greater risk for myocardial infarction with no obstructive atherosclerosis (MINOCA) in an age- and race-adjusted analysis. All of these were statistically significant differences.
Of note, however, in a multivariate analysis fully adjusted for standard cardiovascular risk factors, as well as hypercoagulability, preterm birth, grand multiparity, and insurance status, placental abruption was independently associated with a 2.14-fold risk of MINOCA, but it was no longer linked to significantly increased risks of the other cardiovascular events.
The implication is that the increased risk of these other forms of cardiovascular disease is mediated through the women’s increased prevalence of the traditional cardiovascular risk factors, whereas a novel mechanism – most likely microvascular dysfunction – underlies the association between placental abruption and MINOCA, according to Dr. Healy.
He plans to extend this research by taking a look at the relationship between placental abruption and the various subtypes of MINOCA, including coronary dissection, vasospasm, thrombophilia disorders, and stress cardiomyopathy, in order to examine whether the increased risk posed by placental abruption is concentrated in certain forms of MINOCA. Data on MINOCA subtypes were recorded as part of the California project.
He reported having no financial conflicts of interest regarding his study.
REPORTING FROM THE AHA SCIENTIFIC SESSIONS
Key clinical point: Placental abruption is associated with increased risk of maternal cardiovascular events within a few years after delivery.
Major finding: Placental abruption was independently associated with a 2.14-fold increased risk of myocardial infarction with no obstructive atherosclerosis during a median 4.9 years of follow-up.
Study details: This was a retrospective study of more than 1.6 million parous women enrolled in the California Healthcare Cost and Utilization Project, including 15,057 with placental abruption.
Disclosures: The study presenter reported having no financial conflicts of interest.
How to direct refer for GI endoscopy
MAUI, HAWAII – Rheumatologists can save their patients time and the inconvenience of an unnecessary preprocedural office visit with a gastroenterologist by making a direct referral for GI endoscopy when appropriate, according to Uma Mahadevan, MD, professor of medicine at the University of California, San Francisco.
“Many health systems have access issues, and in most accountable care organizations, there’s a need to see patients within 14 days. the gastroenterologist explained at the 2018 Rheumatology Winter Clinical Symposium.
“We’re an open-access endoscopy center at UCSF, and I can’t tell you how many times a patient gets direct referred to us and – the night before the procedure, when we’re preparing for the case – we see that this patient can’t have a procedure tomorrow. Those patients have already done the bowel prep, they’re taking the day off work, they’ve arranged for someone to drive them, and they’re really mad,” said Dr. Mahadevan, who is also the medical director of the UCSF Center for Colitis and Crohn’s Disease.
Sometimes the procedure gets called off because the gastroenterologist sees that it would be inappropriate. For example, it would be inappropriate to perform an endoscopy on a patient with irritable bowel syndrome or fibromyalgia who has already had three negative endoscopic procedures in the past 5 years; alternatively, a screening colonoscopy would be inappropriate for an 80-year-old because the U.S. Preventive Services Task Force gives a class A recommendation for screening colonoscopy only during ages 50-75 years.
Sometimes the physician who made the direct referral failed to include other key information the gastroenterologist needed to have in advance of the procedure. For example, a morbidly obese patient or an individual with significant cardiovascular or pulmonary disease generally needs to have an anesthesiologist present for GI endoscopy, rather than a nurse anesthetist, since the airway is suspect. Similarly, a patient with a severe anxiety disorder or tolerance to pain medication is unlikely to be adequately sedated with the fentanyl and midazolam (Versed) used for moderate sedation in most upper endoscopy and colonoscopy procedures; those individuals are going to require deep sedation with propofol (Diprivan) and assistance in maintaining a patent airway.
“Your patient taking Oxycodone every day is not going to get sedated with fentanyl and midazolam. So you need to put that information on your direct request,” she stressed.
“If your patient has obstructive sleep apnea and is on CPAP at home, or if your patient is on home oxygen, your gastroenterologist needs to know that because those are the patients we bring into the office to evaluate the airway ahead of time,” according to the gastroenterologist.
Also, while routine direct referral for colonoscopy to rule out comorbid inflammatory bowel disease is entirely appropriate in patients with ankylosing spondylitis or other spondyloarthropathies, if they had ankylosing spondylitis in the prebiologic era, then it’s important to include that information.
“If they did, their neck is often dangerous for sedation. They’re very difficult to intubate. That’s something we need to know,” Dr. Mahadevan continued.
Other patient information gastroenterologists want included in the direct referral: Is the patient on daily aspirin and/or a thienopyridine antiplatelet agent or on oral anticoagulation with warfarin or one of the newer direct-acting oral anticoagulants? American Society for Gastrointestinal Endoscopy guidelines have detailed how to manage antithrombotic agents in patients undergoing GI endoscopy, including when and how to bridge with low-molecular-weight heparin in the days prior to the procedure (Gastrointest Endosc. 2016 Jan;83[1]:3-16). Of note, the guidelines rate diagnostic esophagogastroduodenoscopy (EGD) and colonoscopy, even with biopsies taken, as low-bleeding-risk procedures that therefore don’t require stopping antithrombotic therapy.
In addition to screening or surveillance colonoscopy, rheumatologists might also direct refer patients for GI endoscopy because they have iron-deficiency anemia, in which case evaluation by both EGD and colonoscopy is necessary. Direct referral for EGD in patients with celiac disease is appropriate. Acute GI bleeding is best handled via direct referral for colonoscopy in a patient with hematochezia and for EGD in the setting of melena. Direct referral for endoscopy is also warranted in patients with polymyalgia rheumatica or dermatomyositis, where the indication is to rule out associated malignancy.
Dr. Mahadevan reported having no financial conflicts regarding her presentation.
MAUI, HAWAII – Rheumatologists can save their patients time and the inconvenience of an unnecessary preprocedural office visit with a gastroenterologist by making a direct referral for GI endoscopy when appropriate, according to Uma Mahadevan, MD, professor of medicine at the University of California, San Francisco.
“Many health systems have access issues, and in most accountable care organizations, there’s a need to see patients within 14 days. the gastroenterologist explained at the 2018 Rheumatology Winter Clinical Symposium.
“We’re an open-access endoscopy center at UCSF, and I can’t tell you how many times a patient gets direct referred to us and – the night before the procedure, when we’re preparing for the case – we see that this patient can’t have a procedure tomorrow. Those patients have already done the bowel prep, they’re taking the day off work, they’ve arranged for someone to drive them, and they’re really mad,” said Dr. Mahadevan, who is also the medical director of the UCSF Center for Colitis and Crohn’s Disease.
Sometimes the procedure gets called off because the gastroenterologist sees that it would be inappropriate. For example, it would be inappropriate to perform an endoscopy on a patient with irritable bowel syndrome or fibromyalgia who has already had three negative endoscopic procedures in the past 5 years; alternatively, a screening colonoscopy would be inappropriate for an 80-year-old because the U.S. Preventive Services Task Force gives a class A recommendation for screening colonoscopy only during ages 50-75 years.
Sometimes the physician who made the direct referral failed to include other key information the gastroenterologist needed to have in advance of the procedure. For example, a morbidly obese patient or an individual with significant cardiovascular or pulmonary disease generally needs to have an anesthesiologist present for GI endoscopy, rather than a nurse anesthetist, since the airway is suspect. Similarly, a patient with a severe anxiety disorder or tolerance to pain medication is unlikely to be adequately sedated with the fentanyl and midazolam (Versed) used for moderate sedation in most upper endoscopy and colonoscopy procedures; those individuals are going to require deep sedation with propofol (Diprivan) and assistance in maintaining a patent airway.
“Your patient taking Oxycodone every day is not going to get sedated with fentanyl and midazolam. So you need to put that information on your direct request,” she stressed.
“If your patient has obstructive sleep apnea and is on CPAP at home, or if your patient is on home oxygen, your gastroenterologist needs to know that because those are the patients we bring into the office to evaluate the airway ahead of time,” according to the gastroenterologist.
Also, while routine direct referral for colonoscopy to rule out comorbid inflammatory bowel disease is entirely appropriate in patients with ankylosing spondylitis or other spondyloarthropathies, if they had ankylosing spondylitis in the prebiologic era, then it’s important to include that information.
“If they did, their neck is often dangerous for sedation. They’re very difficult to intubate. That’s something we need to know,” Dr. Mahadevan continued.
Other patient information gastroenterologists want included in the direct referral: Is the patient on daily aspirin and/or a thienopyridine antiplatelet agent or on oral anticoagulation with warfarin or one of the newer direct-acting oral anticoagulants? American Society for Gastrointestinal Endoscopy guidelines have detailed how to manage antithrombotic agents in patients undergoing GI endoscopy, including when and how to bridge with low-molecular-weight heparin in the days prior to the procedure (Gastrointest Endosc. 2016 Jan;83[1]:3-16). Of note, the guidelines rate diagnostic esophagogastroduodenoscopy (EGD) and colonoscopy, even with biopsies taken, as low-bleeding-risk procedures that therefore don’t require stopping antithrombotic therapy.
In addition to screening or surveillance colonoscopy, rheumatologists might also direct refer patients for GI endoscopy because they have iron-deficiency anemia, in which case evaluation by both EGD and colonoscopy is necessary. Direct referral for EGD in patients with celiac disease is appropriate. Acute GI bleeding is best handled via direct referral for colonoscopy in a patient with hematochezia and for EGD in the setting of melena. Direct referral for endoscopy is also warranted in patients with polymyalgia rheumatica or dermatomyositis, where the indication is to rule out associated malignancy.
Dr. Mahadevan reported having no financial conflicts regarding her presentation.
MAUI, HAWAII – Rheumatologists can save their patients time and the inconvenience of an unnecessary preprocedural office visit with a gastroenterologist by making a direct referral for GI endoscopy when appropriate, according to Uma Mahadevan, MD, professor of medicine at the University of California, San Francisco.
“Many health systems have access issues, and in most accountable care organizations, there’s a need to see patients within 14 days. the gastroenterologist explained at the 2018 Rheumatology Winter Clinical Symposium.
“We’re an open-access endoscopy center at UCSF, and I can’t tell you how many times a patient gets direct referred to us and – the night before the procedure, when we’re preparing for the case – we see that this patient can’t have a procedure tomorrow. Those patients have already done the bowel prep, they’re taking the day off work, they’ve arranged for someone to drive them, and they’re really mad,” said Dr. Mahadevan, who is also the medical director of the UCSF Center for Colitis and Crohn’s Disease.
Sometimes the procedure gets called off because the gastroenterologist sees that it would be inappropriate. For example, it would be inappropriate to perform an endoscopy on a patient with irritable bowel syndrome or fibromyalgia who has already had three negative endoscopic procedures in the past 5 years; alternatively, a screening colonoscopy would be inappropriate for an 80-year-old because the U.S. Preventive Services Task Force gives a class A recommendation for screening colonoscopy only during ages 50-75 years.
Sometimes the physician who made the direct referral failed to include other key information the gastroenterologist needed to have in advance of the procedure. For example, a morbidly obese patient or an individual with significant cardiovascular or pulmonary disease generally needs to have an anesthesiologist present for GI endoscopy, rather than a nurse anesthetist, since the airway is suspect. Similarly, a patient with a severe anxiety disorder or tolerance to pain medication is unlikely to be adequately sedated with the fentanyl and midazolam (Versed) used for moderate sedation in most upper endoscopy and colonoscopy procedures; those individuals are going to require deep sedation with propofol (Diprivan) and assistance in maintaining a patent airway.
“Your patient taking Oxycodone every day is not going to get sedated with fentanyl and midazolam. So you need to put that information on your direct request,” she stressed.
“If your patient has obstructive sleep apnea and is on CPAP at home, or if your patient is on home oxygen, your gastroenterologist needs to know that because those are the patients we bring into the office to evaluate the airway ahead of time,” according to the gastroenterologist.
Also, while routine direct referral for colonoscopy to rule out comorbid inflammatory bowel disease is entirely appropriate in patients with ankylosing spondylitis or other spondyloarthropathies, if they had ankylosing spondylitis in the prebiologic era, then it’s important to include that information.
“If they did, their neck is often dangerous for sedation. They’re very difficult to intubate. That’s something we need to know,” Dr. Mahadevan continued.
Other patient information gastroenterologists want included in the direct referral: Is the patient on daily aspirin and/or a thienopyridine antiplatelet agent or on oral anticoagulation with warfarin or one of the newer direct-acting oral anticoagulants? American Society for Gastrointestinal Endoscopy guidelines have detailed how to manage antithrombotic agents in patients undergoing GI endoscopy, including when and how to bridge with low-molecular-weight heparin in the days prior to the procedure (Gastrointest Endosc. 2016 Jan;83[1]:3-16). Of note, the guidelines rate diagnostic esophagogastroduodenoscopy (EGD) and colonoscopy, even with biopsies taken, as low-bleeding-risk procedures that therefore don’t require stopping antithrombotic therapy.
In addition to screening or surveillance colonoscopy, rheumatologists might also direct refer patients for GI endoscopy because they have iron-deficiency anemia, in which case evaluation by both EGD and colonoscopy is necessary. Direct referral for EGD in patients with celiac disease is appropriate. Acute GI bleeding is best handled via direct referral for colonoscopy in a patient with hematochezia and for EGD in the setting of melena. Direct referral for endoscopy is also warranted in patients with polymyalgia rheumatica or dermatomyositis, where the indication is to rule out associated malignancy.
Dr. Mahadevan reported having no financial conflicts regarding her presentation.
EXPERT ANALYSIS FROM RWCS 2018
Role of musculoskeletal ultrasound expands in rheumatic diseases
MAUI, HAWAII – Recent studies highlight novel applications of musculoskeletal ultrasound across a broad spectrum of rheumatic diseases beyond the imaging method’s well-established role in diagnosis and follow-up of patients with rheumatoid arthritis, Alvin F. Wells, MD, PhD, said at the 2018 Rheumatology Winter Clinical Symposium.
He cited recently published evidence in support of his contention:
Systemic lupus erythematosus
Portuguese investigators reported that 77% of their study participants with asymptomatic systemic lupus erythematosus (SLE) – that is, no arthralgia or musculoskeletal signs or symptoms on physical examination – demonstrated gray-scale ultrasound evidence of grade 1 or greater synovial hypertrophy of joints in the hands and/or wrists on a semiquantitative 0-3 scale. So did 100% of patients with symptomatic SLE in this small study, in which physicians evaluated 22 joints per person.
Moreover, grade 1 or greater intra-articular power Doppler changes were also detected in one-fifth of the asymptomatic patients and 83% of those with symptomatic SLE. What the researchers considered persuasive ultrasound evidence of synovitis – grade 2 or 3 synovial hypertrophy or at least grade 1 power Doppler findings – was noted in 23% of the asymptomatic SLE patients, 83% of those who were symptomatic, and none of the healthy controls.
The investigators concluded that asymptomatic patients with SLE may present with subclinical joint inflammation that often goes undetected by physical examination and x-ray. They added that ultrasound with power Doppler may be important in disease evaluation and therapeutic monitoring in patients with lupus (Lupus Sci Med. 2017 Jan 19;4[1]:e000184).
For Dr. Wells, the take-home message was clear: “Don’t overlook the hands.”
“In my lupus patients, sure, I look at the hips, making sure there are no subtle signs of osteonecrosis, but I think we often forget to look at the hands. We’re looking at the hair, looking at the mouth, we’re worried about the lungs. But I think we often overlook the synovitis. These patients are going to the ER because they’re having pain in their hands, and they’re getting told, ‘This is fibromyalgia, go back and see your rheumatologist.’ So it’s something to think about: When you’ve got a patient with active lupus, ultrasound may have a role to play,” according to Dr. Wells.
The big unanswered question is whether early aggressive treatment in SLE patients with these synovial abnormalities – that is, a treat-to-target, ultrasound-guided strategy – can limit erosive changes, avoid disease progression, and improve functional outcomes, as is now known to be the case in RA. Long-term studies will be required to find out, he noted.
Ultrasound of parotid glands in suspected Sjögren’s syndrome is biopsy sparing
Members of the European League Against Rheumatism Ultrasound Primary Sjögren’s Syndrome Study Group recently reported that in a prospective study of 103 consecutive outpatients with clinically suspected primary Sjögren’s syndrome, a positive ultrasound examination of the major salivary glands in combination with the presence of anti-SSA/Ro antibodies was highly predictive of positive parotid and labial gland biopsies. Indeed, a positive ultrasound plus anti-SSA/Ro antibodies showed a high predictive value for Sjögren’s syndrome regardless of whether the classification was based upon American College of Rheumatology, American European Consensus Group, or ACR-EULAR criteria (Ann Rheum Dis. 2017;76[11]:1883-9).
“Ophthalmologists, dentists, and primary care physicians frequently refer patients with dry eyes and dry mouth to us to sort out whether they have Sjögren’s syndrome. The data show now that with a positive salivary gland ultrasound score and a positive anti-SSA/Ro antibody test you can avoid the biopsies,” the rheumatologist said.
That’s a fine thing for patients because these biopsies often result in residual numbness and tingling, he added.
Dr. Wells noted that a multicenter European group recently fine-tuned the criteria for an abnormal salivary gland ultrasound score. They identified echogenicity and homogeneity as the two most reliable items on the score. They also reported that the mean time it took five ultrasonographers to perform salivary gland assessments was reasonable at 11-27 minutes (RMD Open. 2017 Jun 9;3[1]:e000364).
“You can do this essentially in an office visit. The changes in the salivary glands are pathognomonic for Sjögren’s – you won’t get it confused with a neoplasm. I schedule these patients for a 15-minute time slot, and based upon the ultrasound and whether they’re positive or negative for anti-SSA/Ro antibodies I can make some decisions from there,” Dr. Wells explained.
He described what to look for on ultrasound: “A normal parotid looks like a homogeneous gray sponge on ultrasound. In Sjögren’s syndrome, you see icepicklike holes in the sponge. And there’s thickening of the intima, so you see blunting of the arterial wave on pulse wave.”
Implications of ultrasound enthesitis in early spondyloarthritis
French rheumatologists reported on the implications of an ultrasound peripheral enthesis assessment in 402 patients with early axial spondyloarthritis in the French DESIR cohort. The ultrasound evaluation covered the lateral epicondyles, Achilles tendon, and superior and inferior patellar ligament entheses. The results were summed up in ultrasound structural and power Doppler scores. In addition, the investigators obtained spine and sacroiliac joint MRI scans and spine x-rays, all scored centrally.
It turned out that ultrasound abnormalities weren’t useful in monitoring axial spondyloarthritis clinical disease activity as reflected in Bath Ankylosing Spondylitis Disease Activity Index scores, nor were the ultrasound structural and power Doppler scores associated with MRI spine inflammatory lesions or sacroiliitis. However, ultrasound enthesophytes were strongly associated with axial syndesmophytes, suggesting that these ultrasound abnormalities might be a marker of disease severity in axial spondyloarthritis (RMD Open. 2017 Sep 7;3[2]:e000482).
“Whether or not by inhibiting these peripheral enthesophytes you’ll ultimately inhibit further enthesophytes or syndesmophytes from forming is yet to be seen,” Dr. Wells cautioned.
He added, however, that a recent short-term, randomized, placebo-controlled trial in 185 patients with nonradiographic axial spondyloarthritis holds hope in that regard. Investigators in the ongoing multicenter EMBARK (Effect of Etanercept on Symptoms and Objective Inflammation in Nonradiographic Spondyloarthritis) trial reported that treatment with etanercept was associated with a significantly greater reduction in erosions, an increase in backfill, and improved clinical outcomes, compared with placebo, as assessed by MRIs obtained at baseline and 12 weeks.
The investigators viewed these findings as consistent with an early reparative response to the anti–tumor necrosis factor agent, although they noted that understanding of the biologic agent’s true impact on disease progression awaits longer-term follow-up in the 104-week study (Ann Rheum Dis. 2018 Jan;77[1]:78-84).
Dr. Wells reported serving as a consultant to more than half a dozen pharmaceutical companies and receiving research funding from Abbott, Celgene, and UCB.
MAUI, HAWAII – Recent studies highlight novel applications of musculoskeletal ultrasound across a broad spectrum of rheumatic diseases beyond the imaging method’s well-established role in diagnosis and follow-up of patients with rheumatoid arthritis, Alvin F. Wells, MD, PhD, said at the 2018 Rheumatology Winter Clinical Symposium.
He cited recently published evidence in support of his contention:
Systemic lupus erythematosus
Portuguese investigators reported that 77% of their study participants with asymptomatic systemic lupus erythematosus (SLE) – that is, no arthralgia or musculoskeletal signs or symptoms on physical examination – demonstrated gray-scale ultrasound evidence of grade 1 or greater synovial hypertrophy of joints in the hands and/or wrists on a semiquantitative 0-3 scale. So did 100% of patients with symptomatic SLE in this small study, in which physicians evaluated 22 joints per person.
Moreover, grade 1 or greater intra-articular power Doppler changes were also detected in one-fifth of the asymptomatic patients and 83% of those with symptomatic SLE. What the researchers considered persuasive ultrasound evidence of synovitis – grade 2 or 3 synovial hypertrophy or at least grade 1 power Doppler findings – was noted in 23% of the asymptomatic SLE patients, 83% of those who were symptomatic, and none of the healthy controls.
The investigators concluded that asymptomatic patients with SLE may present with subclinical joint inflammation that often goes undetected by physical examination and x-ray. They added that ultrasound with power Doppler may be important in disease evaluation and therapeutic monitoring in patients with lupus (Lupus Sci Med. 2017 Jan 19;4[1]:e000184).
For Dr. Wells, the take-home message was clear: “Don’t overlook the hands.”
“In my lupus patients, sure, I look at the hips, making sure there are no subtle signs of osteonecrosis, but I think we often forget to look at the hands. We’re looking at the hair, looking at the mouth, we’re worried about the lungs. But I think we often overlook the synovitis. These patients are going to the ER because they’re having pain in their hands, and they’re getting told, ‘This is fibromyalgia, go back and see your rheumatologist.’ So it’s something to think about: When you’ve got a patient with active lupus, ultrasound may have a role to play,” according to Dr. Wells.
The big unanswered question is whether early aggressive treatment in SLE patients with these synovial abnormalities – that is, a treat-to-target, ultrasound-guided strategy – can limit erosive changes, avoid disease progression, and improve functional outcomes, as is now known to be the case in RA. Long-term studies will be required to find out, he noted.
Ultrasound of parotid glands in suspected Sjögren’s syndrome is biopsy sparing
Members of the European League Against Rheumatism Ultrasound Primary Sjögren’s Syndrome Study Group recently reported that in a prospective study of 103 consecutive outpatients with clinically suspected primary Sjögren’s syndrome, a positive ultrasound examination of the major salivary glands in combination with the presence of anti-SSA/Ro antibodies was highly predictive of positive parotid and labial gland biopsies. Indeed, a positive ultrasound plus anti-SSA/Ro antibodies showed a high predictive value for Sjögren’s syndrome regardless of whether the classification was based upon American College of Rheumatology, American European Consensus Group, or ACR-EULAR criteria (Ann Rheum Dis. 2017;76[11]:1883-9).
“Ophthalmologists, dentists, and primary care physicians frequently refer patients with dry eyes and dry mouth to us to sort out whether they have Sjögren’s syndrome. The data show now that with a positive salivary gland ultrasound score and a positive anti-SSA/Ro antibody test you can avoid the biopsies,” the rheumatologist said.
That’s a fine thing for patients because these biopsies often result in residual numbness and tingling, he added.
Dr. Wells noted that a multicenter European group recently fine-tuned the criteria for an abnormal salivary gland ultrasound score. They identified echogenicity and homogeneity as the two most reliable items on the score. They also reported that the mean time it took five ultrasonographers to perform salivary gland assessments was reasonable at 11-27 minutes (RMD Open. 2017 Jun 9;3[1]:e000364).
“You can do this essentially in an office visit. The changes in the salivary glands are pathognomonic for Sjögren’s – you won’t get it confused with a neoplasm. I schedule these patients for a 15-minute time slot, and based upon the ultrasound and whether they’re positive or negative for anti-SSA/Ro antibodies I can make some decisions from there,” Dr. Wells explained.
He described what to look for on ultrasound: “A normal parotid looks like a homogeneous gray sponge on ultrasound. In Sjögren’s syndrome, you see icepicklike holes in the sponge. And there’s thickening of the intima, so you see blunting of the arterial wave on pulse wave.”
Implications of ultrasound enthesitis in early spondyloarthritis
French rheumatologists reported on the implications of an ultrasound peripheral enthesis assessment in 402 patients with early axial spondyloarthritis in the French DESIR cohort. The ultrasound evaluation covered the lateral epicondyles, Achilles tendon, and superior and inferior patellar ligament entheses. The results were summed up in ultrasound structural and power Doppler scores. In addition, the investigators obtained spine and sacroiliac joint MRI scans and spine x-rays, all scored centrally.
It turned out that ultrasound abnormalities weren’t useful in monitoring axial spondyloarthritis clinical disease activity as reflected in Bath Ankylosing Spondylitis Disease Activity Index scores, nor were the ultrasound structural and power Doppler scores associated with MRI spine inflammatory lesions or sacroiliitis. However, ultrasound enthesophytes were strongly associated with axial syndesmophytes, suggesting that these ultrasound abnormalities might be a marker of disease severity in axial spondyloarthritis (RMD Open. 2017 Sep 7;3[2]:e000482).
“Whether or not by inhibiting these peripheral enthesophytes you’ll ultimately inhibit further enthesophytes or syndesmophytes from forming is yet to be seen,” Dr. Wells cautioned.
He added, however, that a recent short-term, randomized, placebo-controlled trial in 185 patients with nonradiographic axial spondyloarthritis holds hope in that regard. Investigators in the ongoing multicenter EMBARK (Effect of Etanercept on Symptoms and Objective Inflammation in Nonradiographic Spondyloarthritis) trial reported that treatment with etanercept was associated with a significantly greater reduction in erosions, an increase in backfill, and improved clinical outcomes, compared with placebo, as assessed by MRIs obtained at baseline and 12 weeks.
The investigators viewed these findings as consistent with an early reparative response to the anti–tumor necrosis factor agent, although they noted that understanding of the biologic agent’s true impact on disease progression awaits longer-term follow-up in the 104-week study (Ann Rheum Dis. 2018 Jan;77[1]:78-84).
Dr. Wells reported serving as a consultant to more than half a dozen pharmaceutical companies and receiving research funding from Abbott, Celgene, and UCB.
MAUI, HAWAII – Recent studies highlight novel applications of musculoskeletal ultrasound across a broad spectrum of rheumatic diseases beyond the imaging method’s well-established role in diagnosis and follow-up of patients with rheumatoid arthritis, Alvin F. Wells, MD, PhD, said at the 2018 Rheumatology Winter Clinical Symposium.
He cited recently published evidence in support of his contention:
Systemic lupus erythematosus
Portuguese investigators reported that 77% of their study participants with asymptomatic systemic lupus erythematosus (SLE) – that is, no arthralgia or musculoskeletal signs or symptoms on physical examination – demonstrated gray-scale ultrasound evidence of grade 1 or greater synovial hypertrophy of joints in the hands and/or wrists on a semiquantitative 0-3 scale. So did 100% of patients with symptomatic SLE in this small study, in which physicians evaluated 22 joints per person.
Moreover, grade 1 or greater intra-articular power Doppler changes were also detected in one-fifth of the asymptomatic patients and 83% of those with symptomatic SLE. What the researchers considered persuasive ultrasound evidence of synovitis – grade 2 or 3 synovial hypertrophy or at least grade 1 power Doppler findings – was noted in 23% of the asymptomatic SLE patients, 83% of those who were symptomatic, and none of the healthy controls.
The investigators concluded that asymptomatic patients with SLE may present with subclinical joint inflammation that often goes undetected by physical examination and x-ray. They added that ultrasound with power Doppler may be important in disease evaluation and therapeutic monitoring in patients with lupus (Lupus Sci Med. 2017 Jan 19;4[1]:e000184).
For Dr. Wells, the take-home message was clear: “Don’t overlook the hands.”
“In my lupus patients, sure, I look at the hips, making sure there are no subtle signs of osteonecrosis, but I think we often forget to look at the hands. We’re looking at the hair, looking at the mouth, we’re worried about the lungs. But I think we often overlook the synovitis. These patients are going to the ER because they’re having pain in their hands, and they’re getting told, ‘This is fibromyalgia, go back and see your rheumatologist.’ So it’s something to think about: When you’ve got a patient with active lupus, ultrasound may have a role to play,” according to Dr. Wells.
The big unanswered question is whether early aggressive treatment in SLE patients with these synovial abnormalities – that is, a treat-to-target, ultrasound-guided strategy – can limit erosive changes, avoid disease progression, and improve functional outcomes, as is now known to be the case in RA. Long-term studies will be required to find out, he noted.
Ultrasound of parotid glands in suspected Sjögren’s syndrome is biopsy sparing
Members of the European League Against Rheumatism Ultrasound Primary Sjögren’s Syndrome Study Group recently reported that in a prospective study of 103 consecutive outpatients with clinically suspected primary Sjögren’s syndrome, a positive ultrasound examination of the major salivary glands in combination with the presence of anti-SSA/Ro antibodies was highly predictive of positive parotid and labial gland biopsies. Indeed, a positive ultrasound plus anti-SSA/Ro antibodies showed a high predictive value for Sjögren’s syndrome regardless of whether the classification was based upon American College of Rheumatology, American European Consensus Group, or ACR-EULAR criteria (Ann Rheum Dis. 2017;76[11]:1883-9).
“Ophthalmologists, dentists, and primary care physicians frequently refer patients with dry eyes and dry mouth to us to sort out whether they have Sjögren’s syndrome. The data show now that with a positive salivary gland ultrasound score and a positive anti-SSA/Ro antibody test you can avoid the biopsies,” the rheumatologist said.
That’s a fine thing for patients because these biopsies often result in residual numbness and tingling, he added.
Dr. Wells noted that a multicenter European group recently fine-tuned the criteria for an abnormal salivary gland ultrasound score. They identified echogenicity and homogeneity as the two most reliable items on the score. They also reported that the mean time it took five ultrasonographers to perform salivary gland assessments was reasonable at 11-27 minutes (RMD Open. 2017 Jun 9;3[1]:e000364).
“You can do this essentially in an office visit. The changes in the salivary glands are pathognomonic for Sjögren’s – you won’t get it confused with a neoplasm. I schedule these patients for a 15-minute time slot, and based upon the ultrasound and whether they’re positive or negative for anti-SSA/Ro antibodies I can make some decisions from there,” Dr. Wells explained.
He described what to look for on ultrasound: “A normal parotid looks like a homogeneous gray sponge on ultrasound. In Sjögren’s syndrome, you see icepicklike holes in the sponge. And there’s thickening of the intima, so you see blunting of the arterial wave on pulse wave.”
Implications of ultrasound enthesitis in early spondyloarthritis
French rheumatologists reported on the implications of an ultrasound peripheral enthesis assessment in 402 patients with early axial spondyloarthritis in the French DESIR cohort. The ultrasound evaluation covered the lateral epicondyles, Achilles tendon, and superior and inferior patellar ligament entheses. The results were summed up in ultrasound structural and power Doppler scores. In addition, the investigators obtained spine and sacroiliac joint MRI scans and spine x-rays, all scored centrally.
It turned out that ultrasound abnormalities weren’t useful in monitoring axial spondyloarthritis clinical disease activity as reflected in Bath Ankylosing Spondylitis Disease Activity Index scores, nor were the ultrasound structural and power Doppler scores associated with MRI spine inflammatory lesions or sacroiliitis. However, ultrasound enthesophytes were strongly associated with axial syndesmophytes, suggesting that these ultrasound abnormalities might be a marker of disease severity in axial spondyloarthritis (RMD Open. 2017 Sep 7;3[2]:e000482).
“Whether or not by inhibiting these peripheral enthesophytes you’ll ultimately inhibit further enthesophytes or syndesmophytes from forming is yet to be seen,” Dr. Wells cautioned.
He added, however, that a recent short-term, randomized, placebo-controlled trial in 185 patients with nonradiographic axial spondyloarthritis holds hope in that regard. Investigators in the ongoing multicenter EMBARK (Effect of Etanercept on Symptoms and Objective Inflammation in Nonradiographic Spondyloarthritis) trial reported that treatment with etanercept was associated with a significantly greater reduction in erosions, an increase in backfill, and improved clinical outcomes, compared with placebo, as assessed by MRIs obtained at baseline and 12 weeks.
The investigators viewed these findings as consistent with an early reparative response to the anti–tumor necrosis factor agent, although they noted that understanding of the biologic agent’s true impact on disease progression awaits longer-term follow-up in the 104-week study (Ann Rheum Dis. 2018 Jan;77[1]:78-84).
Dr. Wells reported serving as a consultant to more than half a dozen pharmaceutical companies and receiving research funding from Abbott, Celgene, and UCB.
EXPERT ANALYSIS FROM RWCS 2018
TNF inhibitors curb spinal x-ray progression in ankylosing spondylitis
MAUI, HAWAII – How long do patients with ankylosing spondylitis need to be on a tumor necrosis factor (TNF) blocker in order to experience clinically meaningful inhibition of spinal x-ray progression?
At least 2 years, Orrin M. Troum, MD, said at the 2018 Rheumatology Winter Clinical Symposium.
He cited a study by the rheumatologists of the Swiss Clinical Quality Management Program which he considers one of the recent highlights in rheumatologic imaging.
The mean increase in mSASSS was 0.9 units in 2 years. Prior use of a TNF inhibitor reduced the likelihood of progression by 50% in a multivariate analysis, observed Dr. Troum, a rheumatologist at the University of Southern California, Los Angeles, who is also in private practice in Santa Monica, Calif.
Responders to anti-TNF therapy as defined by an Ankylosing Spondylitis Disease Activity Score (ASDAS) of 2.1 or less at the beginning of a 2-year radiographic interval had a mean mSASSS progression of just 0.31 units in the next 2 years, compared with a 1.45-unit increase in nonresponders to anti-TNF therapy with an ASDAS score above 2.1.
Moreover, patients on anti-TNF therapy who achieved inactive disease status as defined by an ASDAS of 1.3 or less at the beginning of the next 2-year radiographic interval experienced essentially no radiographic progression during that interval, with a mean mSASSS increase of just 0.01 units as compared with a 0.52-unit increase in those with an ASDAS of 1.3-2.1. The inference, according to the investigators, is that the reduction in spinal x-ray progression associated with TNF inhibitor (TNFi) therapy was mediated by the biologic therapy’s inhibitory effect on disease activity.
“We present important clues concerning the period of time needed before the inhibitory effects can be objectified: around 2 years of continuous TNFi use, as there was no impact of TNFi treatment during a 2-year radiographic interval, while there was an effect if the treatment was started before this interval. ... Our study suggests that [an ASDAS of 1.3 or less] might be an adequate target, if the goal of treatment is inhibition of further spinal radiographic damage in addition to control of signs and symptoms, ” according to the investigators (Ann Rheum Dis. 2018 Jan;77[1]:63-9).
Dr. Troum reported serving as a consultant to and/or research grant recipient from more than half a dozen pharmaceutical companies.
MAUI, HAWAII – How long do patients with ankylosing spondylitis need to be on a tumor necrosis factor (TNF) blocker in order to experience clinically meaningful inhibition of spinal x-ray progression?
At least 2 years, Orrin M. Troum, MD, said at the 2018 Rheumatology Winter Clinical Symposium.
He cited a study by the rheumatologists of the Swiss Clinical Quality Management Program which he considers one of the recent highlights in rheumatologic imaging.
The mean increase in mSASSS was 0.9 units in 2 years. Prior use of a TNF inhibitor reduced the likelihood of progression by 50% in a multivariate analysis, observed Dr. Troum, a rheumatologist at the University of Southern California, Los Angeles, who is also in private practice in Santa Monica, Calif.
Responders to anti-TNF therapy as defined by an Ankylosing Spondylitis Disease Activity Score (ASDAS) of 2.1 or less at the beginning of a 2-year radiographic interval had a mean mSASSS progression of just 0.31 units in the next 2 years, compared with a 1.45-unit increase in nonresponders to anti-TNF therapy with an ASDAS score above 2.1.
Moreover, patients on anti-TNF therapy who achieved inactive disease status as defined by an ASDAS of 1.3 or less at the beginning of the next 2-year radiographic interval experienced essentially no radiographic progression during that interval, with a mean mSASSS increase of just 0.01 units as compared with a 0.52-unit increase in those with an ASDAS of 1.3-2.1. The inference, according to the investigators, is that the reduction in spinal x-ray progression associated with TNF inhibitor (TNFi) therapy was mediated by the biologic therapy’s inhibitory effect on disease activity.
“We present important clues concerning the period of time needed before the inhibitory effects can be objectified: around 2 years of continuous TNFi use, as there was no impact of TNFi treatment during a 2-year radiographic interval, while there was an effect if the treatment was started before this interval. ... Our study suggests that [an ASDAS of 1.3 or less] might be an adequate target, if the goal of treatment is inhibition of further spinal radiographic damage in addition to control of signs and symptoms, ” according to the investigators (Ann Rheum Dis. 2018 Jan;77[1]:63-9).
Dr. Troum reported serving as a consultant to and/or research grant recipient from more than half a dozen pharmaceutical companies.
MAUI, HAWAII – How long do patients with ankylosing spondylitis need to be on a tumor necrosis factor (TNF) blocker in order to experience clinically meaningful inhibition of spinal x-ray progression?
At least 2 years, Orrin M. Troum, MD, said at the 2018 Rheumatology Winter Clinical Symposium.
He cited a study by the rheumatologists of the Swiss Clinical Quality Management Program which he considers one of the recent highlights in rheumatologic imaging.
The mean increase in mSASSS was 0.9 units in 2 years. Prior use of a TNF inhibitor reduced the likelihood of progression by 50% in a multivariate analysis, observed Dr. Troum, a rheumatologist at the University of Southern California, Los Angeles, who is also in private practice in Santa Monica, Calif.
Responders to anti-TNF therapy as defined by an Ankylosing Spondylitis Disease Activity Score (ASDAS) of 2.1 or less at the beginning of a 2-year radiographic interval had a mean mSASSS progression of just 0.31 units in the next 2 years, compared with a 1.45-unit increase in nonresponders to anti-TNF therapy with an ASDAS score above 2.1.
Moreover, patients on anti-TNF therapy who achieved inactive disease status as defined by an ASDAS of 1.3 or less at the beginning of the next 2-year radiographic interval experienced essentially no radiographic progression during that interval, with a mean mSASSS increase of just 0.01 units as compared with a 0.52-unit increase in those with an ASDAS of 1.3-2.1. The inference, according to the investigators, is that the reduction in spinal x-ray progression associated with TNF inhibitor (TNFi) therapy was mediated by the biologic therapy’s inhibitory effect on disease activity.
“We present important clues concerning the period of time needed before the inhibitory effects can be objectified: around 2 years of continuous TNFi use, as there was no impact of TNFi treatment during a 2-year radiographic interval, while there was an effect if the treatment was started before this interval. ... Our study suggests that [an ASDAS of 1.3 or less] might be an adequate target, if the goal of treatment is inhibition of further spinal radiographic damage in addition to control of signs and symptoms, ” according to the investigators (Ann Rheum Dis. 2018 Jan;77[1]:63-9).
Dr. Troum reported serving as a consultant to and/or research grant recipient from more than half a dozen pharmaceutical companies.
EXPERT ANALYSIS FROM RWCS 2018
Badly behaved neutrophils are novel target in rheumatic diseases
MAUI, HAWAII – For most of her career as a pediatric rheumatologist and immunologist, Anne M. Stevens, MD, PhD, didn’t find neutrophils terribly interesting.
“I’m more of a T-cell person. T cells are very precise, they’re regulated, they’re very sophisticated cells. Neutrophils are like these bumbling idiots that just come in and hit everything in sight and cause all sorts of damage,” she observed at the 2018 Rheumatology Winter Clinical Symposium.
Recently, however, she’s changed her mind. Research in the past few years demonstrates that there’s a lot more to neutrophils than previously known. Neutrophils are not only the first-responder immune cells to acutely inflamed tissue, as has long been recognized, but they also play a huge role in initiating and perpetuating chronic inflammation. Indeed, neutrophils figure prominently in the pathogenesis of rheumatoid arthritis, systemic lupus erythematosus (SLE), antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis, and perhaps in major nonautoimmune diseases as well, including atherosclerosis, type 1 diabetes, thrombosis, and some forms of kidney disease, explained Dr. Stevens, chief of pediatric rheumatology at the University of Washington, Seattle.
Indeed, it’s now clear that neutrophils can either die quietly or become activated in death by creating neutrophil extracellular traps, or NETs, in a process called NETosis. Even though the activated neutrophil is dead, its exteriorized NETs continue to function, grabbing and killing bacterial pathogens. But the NETs also attract immune cells. These NETs are long strands of sticky DNA containing chromatin, histones, elastase, myeloperoxidase, hypercitrullinated proteins, and other autoantigens. NETosis exposes these autoantigens to the immune system, with resultant generation of autoimmune responses in predisposed individuals.
Much detail has been learned about this process. For example, one type of neutrophil death results from lymphokine-activated killer cells releasing perforin, which pokes holes in the neutrophil cell membrane, allowing an influx of calcium. The inflow of calcium triggers activation of peptidyl arginine deiminases, and these enzymes in turn cause hypercitrullination of autoantigens, leading to formation of anti–citrullinated peptide autoantibodies (ACPAs). These ACPAs cause inflammation by inducing complement activation and binding to Fc gamma receptors on phagocytes.
Investigators at the Systemic Autoimmunity Branch of the National Institute of Arthritis and Musculoskeletal and Skin Diseases and several other research centers have shown that mixing RA synovial fibroblasts with NETs induces production of interleukin-6 and ACPAs. In a mouse model of RA, this leads to cartilage loss in joints, providing a plausible mechanistic explanation for joint damage in RA (Sci Immunol. 2017 Apr;2[10]:eaag3358).
Potential therapeutic strategies targeting NETosis
The various treatment approaches under study aim to either inhibit NET release, curb recruitment of neutrophils for activation, promote migration of neutrophils away from sites of inflammation, or foster efferocytosis.
Among the therapeutic possibilities are calcineurin inhibitors as a means of preventing the influx of calcium into neutrophils, peptidyl arginine deiminase inhibitors such as Cl-amidine to prevent hypercitrullination, complement component 5a-receptor antagonists to decrease NET formation, the myeloperoxidase inhibitor known for now as PF-1355, and N-acetyl cysteine to scavenge proinflammatory reactive oxygen species and thereby reduce NET release.
The key will be to develop highly selective agents that encourage well-behaved neutrophils; across-the-board blockade of neutrophil activity would be terribly immunosuppressive and likely dangerous.
“What if we could block neutrophil recruitment just to the organ we’re worried about? If I’m worried about nephritis, let’s just block neutrophil infiltration into the kidneys. There are drugs being developed that will block the specific types of integrins involved,” Dr. Stevens said.
She reported having no financial conflicts regarding her presentation.
MAUI, HAWAII – For most of her career as a pediatric rheumatologist and immunologist, Anne M. Stevens, MD, PhD, didn’t find neutrophils terribly interesting.
“I’m more of a T-cell person. T cells are very precise, they’re regulated, they’re very sophisticated cells. Neutrophils are like these bumbling idiots that just come in and hit everything in sight and cause all sorts of damage,” she observed at the 2018 Rheumatology Winter Clinical Symposium.
Recently, however, she’s changed her mind. Research in the past few years demonstrates that there’s a lot more to neutrophils than previously known. Neutrophils are not only the first-responder immune cells to acutely inflamed tissue, as has long been recognized, but they also play a huge role in initiating and perpetuating chronic inflammation. Indeed, neutrophils figure prominently in the pathogenesis of rheumatoid arthritis, systemic lupus erythematosus (SLE), antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis, and perhaps in major nonautoimmune diseases as well, including atherosclerosis, type 1 diabetes, thrombosis, and some forms of kidney disease, explained Dr. Stevens, chief of pediatric rheumatology at the University of Washington, Seattle.
Indeed, it’s now clear that neutrophils can either die quietly or become activated in death by creating neutrophil extracellular traps, or NETs, in a process called NETosis. Even though the activated neutrophil is dead, its exteriorized NETs continue to function, grabbing and killing bacterial pathogens. But the NETs also attract immune cells. These NETs are long strands of sticky DNA containing chromatin, histones, elastase, myeloperoxidase, hypercitrullinated proteins, and other autoantigens. NETosis exposes these autoantigens to the immune system, with resultant generation of autoimmune responses in predisposed individuals.
Much detail has been learned about this process. For example, one type of neutrophil death results from lymphokine-activated killer cells releasing perforin, which pokes holes in the neutrophil cell membrane, allowing an influx of calcium. The inflow of calcium triggers activation of peptidyl arginine deiminases, and these enzymes in turn cause hypercitrullination of autoantigens, leading to formation of anti–citrullinated peptide autoantibodies (ACPAs). These ACPAs cause inflammation by inducing complement activation and binding to Fc gamma receptors on phagocytes.
Investigators at the Systemic Autoimmunity Branch of the National Institute of Arthritis and Musculoskeletal and Skin Diseases and several other research centers have shown that mixing RA synovial fibroblasts with NETs induces production of interleukin-6 and ACPAs. In a mouse model of RA, this leads to cartilage loss in joints, providing a plausible mechanistic explanation for joint damage in RA (Sci Immunol. 2017 Apr;2[10]:eaag3358).
Potential therapeutic strategies targeting NETosis
The various treatment approaches under study aim to either inhibit NET release, curb recruitment of neutrophils for activation, promote migration of neutrophils away from sites of inflammation, or foster efferocytosis.
Among the therapeutic possibilities are calcineurin inhibitors as a means of preventing the influx of calcium into neutrophils, peptidyl arginine deiminase inhibitors such as Cl-amidine to prevent hypercitrullination, complement component 5a-receptor antagonists to decrease NET formation, the myeloperoxidase inhibitor known for now as PF-1355, and N-acetyl cysteine to scavenge proinflammatory reactive oxygen species and thereby reduce NET release.
The key will be to develop highly selective agents that encourage well-behaved neutrophils; across-the-board blockade of neutrophil activity would be terribly immunosuppressive and likely dangerous.
“What if we could block neutrophil recruitment just to the organ we’re worried about? If I’m worried about nephritis, let’s just block neutrophil infiltration into the kidneys. There are drugs being developed that will block the specific types of integrins involved,” Dr. Stevens said.
She reported having no financial conflicts regarding her presentation.
MAUI, HAWAII – For most of her career as a pediatric rheumatologist and immunologist, Anne M. Stevens, MD, PhD, didn’t find neutrophils terribly interesting.
“I’m more of a T-cell person. T cells are very precise, they’re regulated, they’re very sophisticated cells. Neutrophils are like these bumbling idiots that just come in and hit everything in sight and cause all sorts of damage,” she observed at the 2018 Rheumatology Winter Clinical Symposium.
Recently, however, she’s changed her mind. Research in the past few years demonstrates that there’s a lot more to neutrophils than previously known. Neutrophils are not only the first-responder immune cells to acutely inflamed tissue, as has long been recognized, but they also play a huge role in initiating and perpetuating chronic inflammation. Indeed, neutrophils figure prominently in the pathogenesis of rheumatoid arthritis, systemic lupus erythematosus (SLE), antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis, and perhaps in major nonautoimmune diseases as well, including atherosclerosis, type 1 diabetes, thrombosis, and some forms of kidney disease, explained Dr. Stevens, chief of pediatric rheumatology at the University of Washington, Seattle.
Indeed, it’s now clear that neutrophils can either die quietly or become activated in death by creating neutrophil extracellular traps, or NETs, in a process called NETosis. Even though the activated neutrophil is dead, its exteriorized NETs continue to function, grabbing and killing bacterial pathogens. But the NETs also attract immune cells. These NETs are long strands of sticky DNA containing chromatin, histones, elastase, myeloperoxidase, hypercitrullinated proteins, and other autoantigens. NETosis exposes these autoantigens to the immune system, with resultant generation of autoimmune responses in predisposed individuals.
Much detail has been learned about this process. For example, one type of neutrophil death results from lymphokine-activated killer cells releasing perforin, which pokes holes in the neutrophil cell membrane, allowing an influx of calcium. The inflow of calcium triggers activation of peptidyl arginine deiminases, and these enzymes in turn cause hypercitrullination of autoantigens, leading to formation of anti–citrullinated peptide autoantibodies (ACPAs). These ACPAs cause inflammation by inducing complement activation and binding to Fc gamma receptors on phagocytes.
Investigators at the Systemic Autoimmunity Branch of the National Institute of Arthritis and Musculoskeletal and Skin Diseases and several other research centers have shown that mixing RA synovial fibroblasts with NETs induces production of interleukin-6 and ACPAs. In a mouse model of RA, this leads to cartilage loss in joints, providing a plausible mechanistic explanation for joint damage in RA (Sci Immunol. 2017 Apr;2[10]:eaag3358).
Potential therapeutic strategies targeting NETosis
The various treatment approaches under study aim to either inhibit NET release, curb recruitment of neutrophils for activation, promote migration of neutrophils away from sites of inflammation, or foster efferocytosis.
Among the therapeutic possibilities are calcineurin inhibitors as a means of preventing the influx of calcium into neutrophils, peptidyl arginine deiminase inhibitors such as Cl-amidine to prevent hypercitrullination, complement component 5a-receptor antagonists to decrease NET formation, the myeloperoxidase inhibitor known for now as PF-1355, and N-acetyl cysteine to scavenge proinflammatory reactive oxygen species and thereby reduce NET release.
The key will be to develop highly selective agents that encourage well-behaved neutrophils; across-the-board blockade of neutrophil activity would be terribly immunosuppressive and likely dangerous.
“What if we could block neutrophil recruitment just to the organ we’re worried about? If I’m worried about nephritis, let’s just block neutrophil infiltration into the kidneys. There are drugs being developed that will block the specific types of integrins involved,” Dr. Stevens said.
She reported having no financial conflicts regarding her presentation.
EXPERT ANALYSIS FROM RWCS 2018
Experts review the year in rheumatology ... and what lies ahead
MAUI, HAWAII – Arthur Kavanaugh, MD, program director for the Rheumatology Winter Clinical Symposium, likes to close out the meeting each year in high style by assembling selected conference faculty to offer their personal picks for the top developments in the field during the past year and make predictions about the year to come.
Here’s how they called it:
The top events in rheumatology during the last year
The rise of oral small molecules: The Janus kinase (JAK) inhibitors and other oral small molecules that have begun reaching the marketplace, with many more in development, will bring a paradigm shift in the treatment not only of rheumatic diseases, but in inflammatory bowel disease and skin diseases as well, predicted Alvin F. Wells, MD, PhD, a rheumatologist at Duke University in Durham, N.C., who is also director of the Rheumatology and Immunotherapy Center in Franklin, Wisc.
“The challenge is whether Medicare will cover the pills the way they cover the infusions and the other things we do,” according to Dr. Wells.
A bevy of new drugs for psoriatic arthritis and psoriasis: “I think the most important advance in the past year was the approval of a profusion of drugs for psoriatic arthritis and psoriasis. It’s really opened up the landscape for us in terms of treatment options. The downside is it’s going to take us a while to sort through which drugs fit where,” noted Eric J. Ruderman, MD, professor of medicine and associate chief of clinical affairs in the division of rheumatology at Northwestern University in Chicago.
“The drug I was most impressed with was tofacitinib [Xeljanz, an oral JAK inhibitor], not just by its effectiveness but by its potential to change the game, and particularly the data in tumor necrosis factor inhibitor inadequate responders. That was pretty solid data. It really opens the way to oral small molecules for joint diseases,” he added.
Interleukin-18 binding protein for monogenic inflammasome diseases: The biggest recent breakthrough in pediatric rheumatology was the Food and Drug Administration’s April 2017 designation of Breakthrough Therapy status for the recombinant human IL-18 binding protein known as tadekinig alfa for monogenic IL-18-associated autoinflammatory conditions, as well as the biologic’s Orphan Drug Designation for treatment of hemophagocytic lymphohistiocytosis, according to Anne M. Stevens, MD, PhD, professor of pediatrics at the University of Washington, Seattle, and chief of pediatric rheumatology at Seattle Children’s Hospital.
Novel treatment concept emerges in severe SLE: The study that knocked the socks off of Martin J. Bergman, MD, in 2017 was the Dutch SymBiose study, presented at both the European League Against Rheumatism and American College of Rheumatology annual meetings. It included just 14 patients with severe refractory SLE – including 10 with lupus nephritis – and tested a treatment strategy of rituximab (Rituxan) followed a few weeks later by a course of belimumab (Benlysta).
“The results were very dramatic, to say the least,” said Dr. Bergman of Drexel University in Philadelphia. Indeed, this one-two therapeutic punch resulted in sharply reduced levels of pathogenic autoantibodies and immune complex-mediated neutrophil extracellular traps while also knocking down very high baseline Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores to near zero, even while enabling patients to discontinue systemic corticosteroids and mycophenolate mofetil (CellCept). Several much larger clinical trials of this regimen and other similar ones are ongoing in an effort to duplicate the results.
Dr. Kavanaugh said the SymBiose study was one of his own top picks for study of the year as well.
Mainstream use of dupilumab (Dupixent) for moderate to severe atopic dermatitis: “This is a total game changer. It’s really changed a lot of people’s lives,” commented George M. Martin, MD, a dermatologist in private practice on Maui.
“Interestingly, historically drugs that started out in your realm later made their way to dermatology, but now we’re seeing the IL-23 inhibitors starting with us and then making their way into rheumatology and gastroenterology. The IL-23 inhibitors are very powerful drugs; when we’re seeing half of our psoriasis patients achieve PASI 100 responses, it’s very exciting. And these are durable responses,” he noted.
The opioid crisis: What’s the most important recent event in rheumatology?
“That’s easy: The biggest thing in all of medicine is the opioid crisis. Whether you recognize it or not, it’s gigantic. It’s $500 billion of the U.S. economy, every year. Forty percent of rheumatoid arthritis patients and 30% with ankylosing spondylitis are on opioids, and what goes along with that is a lot of ugly stuff,” said John J. Cush, MD, professor of medicine and rheumatology at Baylor University in Dallas.
Moreover, the FDA is now so leery of opioids that the agency has set the bar unrealistically high for approval of newer agents offering reduced abuse potential.
“I’ve been involved with or watched at least six FDA advisory panels looking at new, lower abuse-potential opioids in the last couple years. Only one agent got through,” according to Dr. Cush.
Dr. Troum commented, “I really think this whole opioid epidemic started with the campaign to make pain the fifth vital sign back in the 1990s. Some of the pharmaceutical companies took that concept and really ran with it.”
Rapamycin for inclusion body myositis: Dr. Kavanaugh’s pick for study of the year was what he described as “a brilliant presentation” of a French multicenter, placebo-controlled clinical trial of rapamycin for patients with inclusion body myositis at the 2017 ACR annual meeting.
“The French group considers IBM [inclusion body myositis] to be essentially Alzheimer’s disease of the muscle, marked by amyloid deposition. They chose to study rapamycin, which not only has immunosuppressive properties because it binds to mTOR [the mammalian target of rapamycin], but it also has the ability to inhibit amyloid protein deposition,” he explained.
The investigators reported improved 6-minute-walk distance and pulmonary function in the rapamycin group, whereas placebo-treated controls rapidly deteriorated.
“This is an approved drug for other indications, and we scratch our heads with IBM. It’s super nice to have something like that,” Dr. Kavanaugh observed.
A look at what’s in store
More tele-rheumatology: “I think the biggest thing is going to be more tele-rheumatology, more tele-ultrasound. Kaiser Permanente said 49% of their visits last year were virtual visits; that number is just going to grow,” predicted Dr. Wells.
Especially in medically underserved areas of the country, including large rural expanses, demand for remote tele-rheumatologic consults with high-quality imaging is going to increase, he added.
Here come cannabinoids for pain control: Dr. Troum predicted that in the depths of the national opioid epidemic, in a climate that discourages legitimate prescribing of traditional pain medications, rheumatologists can anticipate growing patient demand for cannabidiol and other cannabinoids for pain relief.
“I have patients coming in their 60s, 70s, and 80s – these are not young people – who are whispering to me, ‘Can I use this for my chronic pain?’ I think there’s going to be a big push for ways other than opioids to treat our patients’ pain,” according to Dr. Troum.
Tipping point nears for JAK inhibitors: In 2018, it will become clear just how seriously the Food and Drug Administration views the signal of possible increased venous thromboembolic risk associated with the oral JAK inhibitors for rheumatoid arthritis. The agency is expected to rule on Eli Lilly and Incyte’s resubmitted application for marketing approval for the JAK inhibitor baricitinib, which was tripped up earlier based in part upon VTE concerns.
“I think the big story in 2018 will be how the JAK story shakes out – whether this VTE thing has legs,” Dr. Ruderman predicted. “A sea change could be coming in our field, and it’s not coming next year or the year after, but 10 years from now: Are we going to move past the era of methotrexate and use generic small molecules instead? We’re going to find out within the next year whether that’s going to happen.”
Phase 3 results coming on tocilizumab for systemic sclerosis: “I think we’re going to see some really exciting systemic sclerosis data coming out this year,” Dr. Stevens said. Based upon the positive phase 2 results presented for tocilizumab (Actemra) last year, she’s optimistic that the ongoing phase 3 randomized trial will demonstrate a significant advantage over placebo in lung function. Also, ongoing separate clinical trials are evaluating an antifibrotic drug and rapamycin for systemic sclerosis.
Dr. Bergman, too, has high hopes for these studies: “I think we may finally be getting to a place where we can see effective drugs in systemic sclerosis.”
Amazon, Berkshire Hathaway, and JPMorgan Chase form a nonprofit to improve employee health care: In a recent press conference, the three CEOs weren’t specific about their plans, but Dr. Martin predicted the companies are likely to self-insure, bypassing Cigna and the other major health insurance companies and then contracting with physicians. He forecast that “probably within the next 5 years, what they do is going to affect everybody in this room.”
Rheumatologists will need to master a new mindset: Many rheumatologists have gotten comfortable with an all-tumor necrosis factor inhibitor treatment menu for their patients with moderate or severe rheumatoid arthritis. That’s got to change, according to Dr. Cush.
“We now have two IL-6 inhibitors, two IL-17 inhibitors, and we’ll soon have two JAK inhibitors. That’s going to be a direct threat to the not right- or left-brain, but the TNF-brain rheumatologist who now writes prescriptions for three TNF inhibitors in a row before questioning the efficacy. The idea is you will now be using drugs with other mechanisms of action first-line, or at the very least, second-line, and that’s going to be a paradigm shift for a lot of people,” he explained.
None of the speakers reported having financial conflicts regarding their comments.
MAUI, HAWAII – Arthur Kavanaugh, MD, program director for the Rheumatology Winter Clinical Symposium, likes to close out the meeting each year in high style by assembling selected conference faculty to offer their personal picks for the top developments in the field during the past year and make predictions about the year to come.
Here’s how they called it:
The top events in rheumatology during the last year
The rise of oral small molecules: The Janus kinase (JAK) inhibitors and other oral small molecules that have begun reaching the marketplace, with many more in development, will bring a paradigm shift in the treatment not only of rheumatic diseases, but in inflammatory bowel disease and skin diseases as well, predicted Alvin F. Wells, MD, PhD, a rheumatologist at Duke University in Durham, N.C., who is also director of the Rheumatology and Immunotherapy Center in Franklin, Wisc.
“The challenge is whether Medicare will cover the pills the way they cover the infusions and the other things we do,” according to Dr. Wells.
A bevy of new drugs for psoriatic arthritis and psoriasis: “I think the most important advance in the past year was the approval of a profusion of drugs for psoriatic arthritis and psoriasis. It’s really opened up the landscape for us in terms of treatment options. The downside is it’s going to take us a while to sort through which drugs fit where,” noted Eric J. Ruderman, MD, professor of medicine and associate chief of clinical affairs in the division of rheumatology at Northwestern University in Chicago.
“The drug I was most impressed with was tofacitinib [Xeljanz, an oral JAK inhibitor], not just by its effectiveness but by its potential to change the game, and particularly the data in tumor necrosis factor inhibitor inadequate responders. That was pretty solid data. It really opens the way to oral small molecules for joint diseases,” he added.
Interleukin-18 binding protein for monogenic inflammasome diseases: The biggest recent breakthrough in pediatric rheumatology was the Food and Drug Administration’s April 2017 designation of Breakthrough Therapy status for the recombinant human IL-18 binding protein known as tadekinig alfa for monogenic IL-18-associated autoinflammatory conditions, as well as the biologic’s Orphan Drug Designation for treatment of hemophagocytic lymphohistiocytosis, according to Anne M. Stevens, MD, PhD, professor of pediatrics at the University of Washington, Seattle, and chief of pediatric rheumatology at Seattle Children’s Hospital.
Novel treatment concept emerges in severe SLE: The study that knocked the socks off of Martin J. Bergman, MD, in 2017 was the Dutch SymBiose study, presented at both the European League Against Rheumatism and American College of Rheumatology annual meetings. It included just 14 patients with severe refractory SLE – including 10 with lupus nephritis – and tested a treatment strategy of rituximab (Rituxan) followed a few weeks later by a course of belimumab (Benlysta).
“The results were very dramatic, to say the least,” said Dr. Bergman of Drexel University in Philadelphia. Indeed, this one-two therapeutic punch resulted in sharply reduced levels of pathogenic autoantibodies and immune complex-mediated neutrophil extracellular traps while also knocking down very high baseline Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores to near zero, even while enabling patients to discontinue systemic corticosteroids and mycophenolate mofetil (CellCept). Several much larger clinical trials of this regimen and other similar ones are ongoing in an effort to duplicate the results.
Dr. Kavanaugh said the SymBiose study was one of his own top picks for study of the year as well.
Mainstream use of dupilumab (Dupixent) for moderate to severe atopic dermatitis: “This is a total game changer. It’s really changed a lot of people’s lives,” commented George M. Martin, MD, a dermatologist in private practice on Maui.
“Interestingly, historically drugs that started out in your realm later made their way to dermatology, but now we’re seeing the IL-23 inhibitors starting with us and then making their way into rheumatology and gastroenterology. The IL-23 inhibitors are very powerful drugs; when we’re seeing half of our psoriasis patients achieve PASI 100 responses, it’s very exciting. And these are durable responses,” he noted.
The opioid crisis: What’s the most important recent event in rheumatology?
“That’s easy: The biggest thing in all of medicine is the opioid crisis. Whether you recognize it or not, it’s gigantic. It’s $500 billion of the U.S. economy, every year. Forty percent of rheumatoid arthritis patients and 30% with ankylosing spondylitis are on opioids, and what goes along with that is a lot of ugly stuff,” said John J. Cush, MD, professor of medicine and rheumatology at Baylor University in Dallas.
Moreover, the FDA is now so leery of opioids that the agency has set the bar unrealistically high for approval of newer agents offering reduced abuse potential.
“I’ve been involved with or watched at least six FDA advisory panels looking at new, lower abuse-potential opioids in the last couple years. Only one agent got through,” according to Dr. Cush.
Dr. Troum commented, “I really think this whole opioid epidemic started with the campaign to make pain the fifth vital sign back in the 1990s. Some of the pharmaceutical companies took that concept and really ran with it.”
Rapamycin for inclusion body myositis: Dr. Kavanaugh’s pick for study of the year was what he described as “a brilliant presentation” of a French multicenter, placebo-controlled clinical trial of rapamycin for patients with inclusion body myositis at the 2017 ACR annual meeting.
“The French group considers IBM [inclusion body myositis] to be essentially Alzheimer’s disease of the muscle, marked by amyloid deposition. They chose to study rapamycin, which not only has immunosuppressive properties because it binds to mTOR [the mammalian target of rapamycin], but it also has the ability to inhibit amyloid protein deposition,” he explained.
The investigators reported improved 6-minute-walk distance and pulmonary function in the rapamycin group, whereas placebo-treated controls rapidly deteriorated.
“This is an approved drug for other indications, and we scratch our heads with IBM. It’s super nice to have something like that,” Dr. Kavanaugh observed.
A look at what’s in store
More tele-rheumatology: “I think the biggest thing is going to be more tele-rheumatology, more tele-ultrasound. Kaiser Permanente said 49% of their visits last year were virtual visits; that number is just going to grow,” predicted Dr. Wells.
Especially in medically underserved areas of the country, including large rural expanses, demand for remote tele-rheumatologic consults with high-quality imaging is going to increase, he added.
Here come cannabinoids for pain control: Dr. Troum predicted that in the depths of the national opioid epidemic, in a climate that discourages legitimate prescribing of traditional pain medications, rheumatologists can anticipate growing patient demand for cannabidiol and other cannabinoids for pain relief.
“I have patients coming in their 60s, 70s, and 80s – these are not young people – who are whispering to me, ‘Can I use this for my chronic pain?’ I think there’s going to be a big push for ways other than opioids to treat our patients’ pain,” according to Dr. Troum.
Tipping point nears for JAK inhibitors: In 2018, it will become clear just how seriously the Food and Drug Administration views the signal of possible increased venous thromboembolic risk associated with the oral JAK inhibitors for rheumatoid arthritis. The agency is expected to rule on Eli Lilly and Incyte’s resubmitted application for marketing approval for the JAK inhibitor baricitinib, which was tripped up earlier based in part upon VTE concerns.
“I think the big story in 2018 will be how the JAK story shakes out – whether this VTE thing has legs,” Dr. Ruderman predicted. “A sea change could be coming in our field, and it’s not coming next year or the year after, but 10 years from now: Are we going to move past the era of methotrexate and use generic small molecules instead? We’re going to find out within the next year whether that’s going to happen.”
Phase 3 results coming on tocilizumab for systemic sclerosis: “I think we’re going to see some really exciting systemic sclerosis data coming out this year,” Dr. Stevens said. Based upon the positive phase 2 results presented for tocilizumab (Actemra) last year, she’s optimistic that the ongoing phase 3 randomized trial will demonstrate a significant advantage over placebo in lung function. Also, ongoing separate clinical trials are evaluating an antifibrotic drug and rapamycin for systemic sclerosis.
Dr. Bergman, too, has high hopes for these studies: “I think we may finally be getting to a place where we can see effective drugs in systemic sclerosis.”
Amazon, Berkshire Hathaway, and JPMorgan Chase form a nonprofit to improve employee health care: In a recent press conference, the three CEOs weren’t specific about their plans, but Dr. Martin predicted the companies are likely to self-insure, bypassing Cigna and the other major health insurance companies and then contracting with physicians. He forecast that “probably within the next 5 years, what they do is going to affect everybody in this room.”
Rheumatologists will need to master a new mindset: Many rheumatologists have gotten comfortable with an all-tumor necrosis factor inhibitor treatment menu for their patients with moderate or severe rheumatoid arthritis. That’s got to change, according to Dr. Cush.
“We now have two IL-6 inhibitors, two IL-17 inhibitors, and we’ll soon have two JAK inhibitors. That’s going to be a direct threat to the not right- or left-brain, but the TNF-brain rheumatologist who now writes prescriptions for three TNF inhibitors in a row before questioning the efficacy. The idea is you will now be using drugs with other mechanisms of action first-line, or at the very least, second-line, and that’s going to be a paradigm shift for a lot of people,” he explained.
None of the speakers reported having financial conflicts regarding their comments.
MAUI, HAWAII – Arthur Kavanaugh, MD, program director for the Rheumatology Winter Clinical Symposium, likes to close out the meeting each year in high style by assembling selected conference faculty to offer their personal picks for the top developments in the field during the past year and make predictions about the year to come.
Here’s how they called it:
The top events in rheumatology during the last year
The rise of oral small molecules: The Janus kinase (JAK) inhibitors and other oral small molecules that have begun reaching the marketplace, with many more in development, will bring a paradigm shift in the treatment not only of rheumatic diseases, but in inflammatory bowel disease and skin diseases as well, predicted Alvin F. Wells, MD, PhD, a rheumatologist at Duke University in Durham, N.C., who is also director of the Rheumatology and Immunotherapy Center in Franklin, Wisc.
“The challenge is whether Medicare will cover the pills the way they cover the infusions and the other things we do,” according to Dr. Wells.
A bevy of new drugs for psoriatic arthritis and psoriasis: “I think the most important advance in the past year was the approval of a profusion of drugs for psoriatic arthritis and psoriasis. It’s really opened up the landscape for us in terms of treatment options. The downside is it’s going to take us a while to sort through which drugs fit where,” noted Eric J. Ruderman, MD, professor of medicine and associate chief of clinical affairs in the division of rheumatology at Northwestern University in Chicago.
“The drug I was most impressed with was tofacitinib [Xeljanz, an oral JAK inhibitor], not just by its effectiveness but by its potential to change the game, and particularly the data in tumor necrosis factor inhibitor inadequate responders. That was pretty solid data. It really opens the way to oral small molecules for joint diseases,” he added.
Interleukin-18 binding protein for monogenic inflammasome diseases: The biggest recent breakthrough in pediatric rheumatology was the Food and Drug Administration’s April 2017 designation of Breakthrough Therapy status for the recombinant human IL-18 binding protein known as tadekinig alfa for monogenic IL-18-associated autoinflammatory conditions, as well as the biologic’s Orphan Drug Designation for treatment of hemophagocytic lymphohistiocytosis, according to Anne M. Stevens, MD, PhD, professor of pediatrics at the University of Washington, Seattle, and chief of pediatric rheumatology at Seattle Children’s Hospital.
Novel treatment concept emerges in severe SLE: The study that knocked the socks off of Martin J. Bergman, MD, in 2017 was the Dutch SymBiose study, presented at both the European League Against Rheumatism and American College of Rheumatology annual meetings. It included just 14 patients with severe refractory SLE – including 10 with lupus nephritis – and tested a treatment strategy of rituximab (Rituxan) followed a few weeks later by a course of belimumab (Benlysta).
“The results were very dramatic, to say the least,” said Dr. Bergman of Drexel University in Philadelphia. Indeed, this one-two therapeutic punch resulted in sharply reduced levels of pathogenic autoantibodies and immune complex-mediated neutrophil extracellular traps while also knocking down very high baseline Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores to near zero, even while enabling patients to discontinue systemic corticosteroids and mycophenolate mofetil (CellCept). Several much larger clinical trials of this regimen and other similar ones are ongoing in an effort to duplicate the results.
Dr. Kavanaugh said the SymBiose study was one of his own top picks for study of the year as well.
Mainstream use of dupilumab (Dupixent) for moderate to severe atopic dermatitis: “This is a total game changer. It’s really changed a lot of people’s lives,” commented George M. Martin, MD, a dermatologist in private practice on Maui.
“Interestingly, historically drugs that started out in your realm later made their way to dermatology, but now we’re seeing the IL-23 inhibitors starting with us and then making their way into rheumatology and gastroenterology. The IL-23 inhibitors are very powerful drugs; when we’re seeing half of our psoriasis patients achieve PASI 100 responses, it’s very exciting. And these are durable responses,” he noted.
The opioid crisis: What’s the most important recent event in rheumatology?
“That’s easy: The biggest thing in all of medicine is the opioid crisis. Whether you recognize it or not, it’s gigantic. It’s $500 billion of the U.S. economy, every year. Forty percent of rheumatoid arthritis patients and 30% with ankylosing spondylitis are on opioids, and what goes along with that is a lot of ugly stuff,” said John J. Cush, MD, professor of medicine and rheumatology at Baylor University in Dallas.
Moreover, the FDA is now so leery of opioids that the agency has set the bar unrealistically high for approval of newer agents offering reduced abuse potential.
“I’ve been involved with or watched at least six FDA advisory panels looking at new, lower abuse-potential opioids in the last couple years. Only one agent got through,” according to Dr. Cush.
Dr. Troum commented, “I really think this whole opioid epidemic started with the campaign to make pain the fifth vital sign back in the 1990s. Some of the pharmaceutical companies took that concept and really ran with it.”
Rapamycin for inclusion body myositis: Dr. Kavanaugh’s pick for study of the year was what he described as “a brilliant presentation” of a French multicenter, placebo-controlled clinical trial of rapamycin for patients with inclusion body myositis at the 2017 ACR annual meeting.
“The French group considers IBM [inclusion body myositis] to be essentially Alzheimer’s disease of the muscle, marked by amyloid deposition. They chose to study rapamycin, which not only has immunosuppressive properties because it binds to mTOR [the mammalian target of rapamycin], but it also has the ability to inhibit amyloid protein deposition,” he explained.
The investigators reported improved 6-minute-walk distance and pulmonary function in the rapamycin group, whereas placebo-treated controls rapidly deteriorated.
“This is an approved drug for other indications, and we scratch our heads with IBM. It’s super nice to have something like that,” Dr. Kavanaugh observed.
A look at what’s in store
More tele-rheumatology: “I think the biggest thing is going to be more tele-rheumatology, more tele-ultrasound. Kaiser Permanente said 49% of their visits last year were virtual visits; that number is just going to grow,” predicted Dr. Wells.
Especially in medically underserved areas of the country, including large rural expanses, demand for remote tele-rheumatologic consults with high-quality imaging is going to increase, he added.
Here come cannabinoids for pain control: Dr. Troum predicted that in the depths of the national opioid epidemic, in a climate that discourages legitimate prescribing of traditional pain medications, rheumatologists can anticipate growing patient demand for cannabidiol and other cannabinoids for pain relief.
“I have patients coming in their 60s, 70s, and 80s – these are not young people – who are whispering to me, ‘Can I use this for my chronic pain?’ I think there’s going to be a big push for ways other than opioids to treat our patients’ pain,” according to Dr. Troum.
Tipping point nears for JAK inhibitors: In 2018, it will become clear just how seriously the Food and Drug Administration views the signal of possible increased venous thromboembolic risk associated with the oral JAK inhibitors for rheumatoid arthritis. The agency is expected to rule on Eli Lilly and Incyte’s resubmitted application for marketing approval for the JAK inhibitor baricitinib, which was tripped up earlier based in part upon VTE concerns.
“I think the big story in 2018 will be how the JAK story shakes out – whether this VTE thing has legs,” Dr. Ruderman predicted. “A sea change could be coming in our field, and it’s not coming next year or the year after, but 10 years from now: Are we going to move past the era of methotrexate and use generic small molecules instead? We’re going to find out within the next year whether that’s going to happen.”
Phase 3 results coming on tocilizumab for systemic sclerosis: “I think we’re going to see some really exciting systemic sclerosis data coming out this year,” Dr. Stevens said. Based upon the positive phase 2 results presented for tocilizumab (Actemra) last year, she’s optimistic that the ongoing phase 3 randomized trial will demonstrate a significant advantage over placebo in lung function. Also, ongoing separate clinical trials are evaluating an antifibrotic drug and rapamycin for systemic sclerosis.
Dr. Bergman, too, has high hopes for these studies: “I think we may finally be getting to a place where we can see effective drugs in systemic sclerosis.”
Amazon, Berkshire Hathaway, and JPMorgan Chase form a nonprofit to improve employee health care: In a recent press conference, the three CEOs weren’t specific about their plans, but Dr. Martin predicted the companies are likely to self-insure, bypassing Cigna and the other major health insurance companies and then contracting with physicians. He forecast that “probably within the next 5 years, what they do is going to affect everybody in this room.”
Rheumatologists will need to master a new mindset: Many rheumatologists have gotten comfortable with an all-tumor necrosis factor inhibitor treatment menu for their patients with moderate or severe rheumatoid arthritis. That’s got to change, according to Dr. Cush.
“We now have two IL-6 inhibitors, two IL-17 inhibitors, and we’ll soon have two JAK inhibitors. That’s going to be a direct threat to the not right- or left-brain, but the TNF-brain rheumatologist who now writes prescriptions for three TNF inhibitors in a row before questioning the efficacy. The idea is you will now be using drugs with other mechanisms of action first-line, or at the very least, second-line, and that’s going to be a paradigm shift for a lot of people,” he explained.
None of the speakers reported having financial conflicts regarding their comments.
EXPERT ANALYSIS FROM RWCS 2018
JAK inhibitors for RA: Is VTE risk overblown?
MAUI, HAWAII – Rheumatologists, regulatory agencies, and the pharmaceutical industry all have gone off the deep end in their fretting over what appears to be a low rate of venous thromboembolic events in the major randomized trials of the oral Janus kinase inhibitors for RA, Mark C. Genovese, MD, asserted at the 2018 Rheumatology Winter Clinical Symposium.
“The reality is all of our drugs pose potential risks. Unfortunately, I think that at least for the moment, the field has turned all attention in one direction: VTE [venous thromboembolic] events. I suspect there’s some truth [to the possible associated risk]. Certainly we are seeing these events. The question is, how overdone is this?” according to Dr. Genovese, professor of medicine and cochief of the division of immunology and rheumatology at Stanford (Calif.) University.
“I think the upadacitinib data has been entirely overshadowed by concerns about VTEs,” he said. “In the last year, we saw three significant phase 3 studies on upadacitinib arrive in the rheumatology community, and I think the only thing we talked about was VTEs.”
All parties interested in developing Janus kinase (JAK) inhibitors for the treatment of RA began to freak out about a possible increase in VTEs when in April 2017 the Food and Drug Administration turned down Eli Lilly and Incyte’s initial application for marketing approval of the JAK inhibitor baricitinib. Among the problems the agency cited was evidence of potential thrombotic risk.
The VTE rate in baricitinib clinical trials up to 48 weeks in duration was 0.53 events/100 patient-years, with no significant difference in risk between the2-mg and 4-mg doses. This appears to be a class effect for the oral JAK inhibitors, as low rates of VTE, albeit numerically higher than in placebo-treated controls, have also been recorded in the RA development programs for tofacitinib (Xeljanz) as well as the investigational agents filgotinib and upadacitinib, the rheumatologist noted.
This begs the question of whether these VTE rates are significantly higher than background rates in patients with RA or other rheumatologic diseases, which are known to be elevated relative to the general population. Indeed, a retrospective study of insurance claims data by investigators at Brigham and Women’s Hospital, Boston, concluded that the VTE rate in RA patients was 0.61 events/100 patient-years, 120% greater than in a matched patient population without RA. After fully adjusting for comorbid conditions and demographics, the relative risk increase associated with RA dropped to 40%, still significantly higher than in controls (Arthritis Care Res [Hoboken]. 2013 Oct;65[10]:1600-7).
Similarly, Canadian investigators conducted a meta-analysis of 25 studies with VTE data in patients with RA, systemic lupus erythematosus, Sjögren’s syndrome, systemic sclerosis, or inflammatory myositis. This meta-analysis included 10 studies of more than 5.2 million RA patients and nearly 900,000 controls. The conclusion: each of these rheumatic diseases was associated with a VTE rate more than three times higher than in the general population (Arthritis Res Ther. 2014 Sep 25;16[5]:435).
“Patients with RA are at higher risk for VTE than those without RA. It’s unfortunate, and it’s certainly something I don’t think many of us have thought much about before. It’s something we don’t often get to see and something we don’t like to think about,” the rheumatologist observed.
Dr. Genovese admitted to a degree of personal frustration with the current tunnel vision focus on VTEs in JAK inhibitor trials. At the 2017 annual meeting of the American College of Rheumatology he presented the results of the phase 3 SELECT-BEYOND study in which 499 RA patients who had previously failed to respond or were intolerant to biologic therapy were randomized to once daily upadacitinib at 15 or 30 mg or placebo on top of background methotrexate. At week 12, the ACR 20 response rate was 65% for upadacitinib at 15 mg, 56% at 30 mg, and 28% in placebo-treated controls.
“That’s almost a 40% placebo-adjusted response rate. In fact, it’s the highest response I’ve ever seen in a biologic inadequate-responder population. This really looked pretty good, but I don’t think anyone ever took notice. Why not? Because we were all worried about VTE,” he said.
There were in fact a handful of VTEs in upadacitinib-treated patients, Dr. Genovese was quick to note. But he was more impressed by the week 12 ACR 20 responses in patients who had previously failed on three or more biologics: 71% with upadacitinib at 15 mg and 50% at 30 mg, compared with 23% in controls. Moreover, among patients with a baseline history of failure to respond to anti–interleukin-6 therapy, the week 12 ACR 20 rate was 56% with upadacitinib at 15 mg and 58% at 30 mg, versus 20% in controls.
“This looks like a pretty effective drug for patients who’ve failed everything else in our practice,” he commented.
Dr. Genovese reminded his audience that the rheumatology community has a history of overreacting to safety signals in the early days after introduction of new therapies. Examples: tuberculosis with tumor necrosis factor inhibitors, lymphoma with abatacept (Orencia), lymphoma with anti–tumor necrosis factor agents, and cardiovascular events with anti–interleukin-6 inhibition.
“PML [progressive multifocal leukoencephalopathy] is a breathtaking side effect with rituximab [Rituxan], but we’ve gotten over that. We recognize that it’s a potential problem, but we still prescribe rituximab,” the rheumatologist noted. “We’re probably going to need to address the issue of which of our patients are potentially at higher risk for VTE, and maybe we avoid this class in those patients. Like we now do as we look at patients we think are at increased risk for infection, or multiple sclerosis, or TB, we may also need to think of VTE risk.”
But , he argued. There is a pressing unmet need for new therapies for RA with novel mechanisms of action. Only about one-half of patients on contemporary biologic therapies are still on that agent 5 years after initiating therapy.
“Virtually all our patients are partial responders. Everybody gets some benefit. But true remission is achieved by only a minority,” Dr. Genovese said. “The gap between where we are and where we want to be is actually much greater than we often perceive.”
He reported having financial relationships with AbbVie, which is developing upadacitinib, and more than a dozen other medical companies.
MAUI, HAWAII – Rheumatologists, regulatory agencies, and the pharmaceutical industry all have gone off the deep end in their fretting over what appears to be a low rate of venous thromboembolic events in the major randomized trials of the oral Janus kinase inhibitors for RA, Mark C. Genovese, MD, asserted at the 2018 Rheumatology Winter Clinical Symposium.
“The reality is all of our drugs pose potential risks. Unfortunately, I think that at least for the moment, the field has turned all attention in one direction: VTE [venous thromboembolic] events. I suspect there’s some truth [to the possible associated risk]. Certainly we are seeing these events. The question is, how overdone is this?” according to Dr. Genovese, professor of medicine and cochief of the division of immunology and rheumatology at Stanford (Calif.) University.
“I think the upadacitinib data has been entirely overshadowed by concerns about VTEs,” he said. “In the last year, we saw three significant phase 3 studies on upadacitinib arrive in the rheumatology community, and I think the only thing we talked about was VTEs.”
All parties interested in developing Janus kinase (JAK) inhibitors for the treatment of RA began to freak out about a possible increase in VTEs when in April 2017 the Food and Drug Administration turned down Eli Lilly and Incyte’s initial application for marketing approval of the JAK inhibitor baricitinib. Among the problems the agency cited was evidence of potential thrombotic risk.
The VTE rate in baricitinib clinical trials up to 48 weeks in duration was 0.53 events/100 patient-years, with no significant difference in risk between the2-mg and 4-mg doses. This appears to be a class effect for the oral JAK inhibitors, as low rates of VTE, albeit numerically higher than in placebo-treated controls, have also been recorded in the RA development programs for tofacitinib (Xeljanz) as well as the investigational agents filgotinib and upadacitinib, the rheumatologist noted.
This begs the question of whether these VTE rates are significantly higher than background rates in patients with RA or other rheumatologic diseases, which are known to be elevated relative to the general population. Indeed, a retrospective study of insurance claims data by investigators at Brigham and Women’s Hospital, Boston, concluded that the VTE rate in RA patients was 0.61 events/100 patient-years, 120% greater than in a matched patient population without RA. After fully adjusting for comorbid conditions and demographics, the relative risk increase associated with RA dropped to 40%, still significantly higher than in controls (Arthritis Care Res [Hoboken]. 2013 Oct;65[10]:1600-7).
Similarly, Canadian investigators conducted a meta-analysis of 25 studies with VTE data in patients with RA, systemic lupus erythematosus, Sjögren’s syndrome, systemic sclerosis, or inflammatory myositis. This meta-analysis included 10 studies of more than 5.2 million RA patients and nearly 900,000 controls. The conclusion: each of these rheumatic diseases was associated with a VTE rate more than three times higher than in the general population (Arthritis Res Ther. 2014 Sep 25;16[5]:435).
“Patients with RA are at higher risk for VTE than those without RA. It’s unfortunate, and it’s certainly something I don’t think many of us have thought much about before. It’s something we don’t often get to see and something we don’t like to think about,” the rheumatologist observed.
Dr. Genovese admitted to a degree of personal frustration with the current tunnel vision focus on VTEs in JAK inhibitor trials. At the 2017 annual meeting of the American College of Rheumatology he presented the results of the phase 3 SELECT-BEYOND study in which 499 RA patients who had previously failed to respond or were intolerant to biologic therapy were randomized to once daily upadacitinib at 15 or 30 mg or placebo on top of background methotrexate. At week 12, the ACR 20 response rate was 65% for upadacitinib at 15 mg, 56% at 30 mg, and 28% in placebo-treated controls.
“That’s almost a 40% placebo-adjusted response rate. In fact, it’s the highest response I’ve ever seen in a biologic inadequate-responder population. This really looked pretty good, but I don’t think anyone ever took notice. Why not? Because we were all worried about VTE,” he said.
There were in fact a handful of VTEs in upadacitinib-treated patients, Dr. Genovese was quick to note. But he was more impressed by the week 12 ACR 20 responses in patients who had previously failed on three or more biologics: 71% with upadacitinib at 15 mg and 50% at 30 mg, compared with 23% in controls. Moreover, among patients with a baseline history of failure to respond to anti–interleukin-6 therapy, the week 12 ACR 20 rate was 56% with upadacitinib at 15 mg and 58% at 30 mg, versus 20% in controls.
“This looks like a pretty effective drug for patients who’ve failed everything else in our practice,” he commented.
Dr. Genovese reminded his audience that the rheumatology community has a history of overreacting to safety signals in the early days after introduction of new therapies. Examples: tuberculosis with tumor necrosis factor inhibitors, lymphoma with abatacept (Orencia), lymphoma with anti–tumor necrosis factor agents, and cardiovascular events with anti–interleukin-6 inhibition.
“PML [progressive multifocal leukoencephalopathy] is a breathtaking side effect with rituximab [Rituxan], but we’ve gotten over that. We recognize that it’s a potential problem, but we still prescribe rituximab,” the rheumatologist noted. “We’re probably going to need to address the issue of which of our patients are potentially at higher risk for VTE, and maybe we avoid this class in those patients. Like we now do as we look at patients we think are at increased risk for infection, or multiple sclerosis, or TB, we may also need to think of VTE risk.”
But , he argued. There is a pressing unmet need for new therapies for RA with novel mechanisms of action. Only about one-half of patients on contemporary biologic therapies are still on that agent 5 years after initiating therapy.
“Virtually all our patients are partial responders. Everybody gets some benefit. But true remission is achieved by only a minority,” Dr. Genovese said. “The gap between where we are and where we want to be is actually much greater than we often perceive.”
He reported having financial relationships with AbbVie, which is developing upadacitinib, and more than a dozen other medical companies.
MAUI, HAWAII – Rheumatologists, regulatory agencies, and the pharmaceutical industry all have gone off the deep end in their fretting over what appears to be a low rate of venous thromboembolic events in the major randomized trials of the oral Janus kinase inhibitors for RA, Mark C. Genovese, MD, asserted at the 2018 Rheumatology Winter Clinical Symposium.
“The reality is all of our drugs pose potential risks. Unfortunately, I think that at least for the moment, the field has turned all attention in one direction: VTE [venous thromboembolic] events. I suspect there’s some truth [to the possible associated risk]. Certainly we are seeing these events. The question is, how overdone is this?” according to Dr. Genovese, professor of medicine and cochief of the division of immunology and rheumatology at Stanford (Calif.) University.
“I think the upadacitinib data has been entirely overshadowed by concerns about VTEs,” he said. “In the last year, we saw three significant phase 3 studies on upadacitinib arrive in the rheumatology community, and I think the only thing we talked about was VTEs.”
All parties interested in developing Janus kinase (JAK) inhibitors for the treatment of RA began to freak out about a possible increase in VTEs when in April 2017 the Food and Drug Administration turned down Eli Lilly and Incyte’s initial application for marketing approval of the JAK inhibitor baricitinib. Among the problems the agency cited was evidence of potential thrombotic risk.
The VTE rate in baricitinib clinical trials up to 48 weeks in duration was 0.53 events/100 patient-years, with no significant difference in risk between the2-mg and 4-mg doses. This appears to be a class effect for the oral JAK inhibitors, as low rates of VTE, albeit numerically higher than in placebo-treated controls, have also been recorded in the RA development programs for tofacitinib (Xeljanz) as well as the investigational agents filgotinib and upadacitinib, the rheumatologist noted.
This begs the question of whether these VTE rates are significantly higher than background rates in patients with RA or other rheumatologic diseases, which are known to be elevated relative to the general population. Indeed, a retrospective study of insurance claims data by investigators at Brigham and Women’s Hospital, Boston, concluded that the VTE rate in RA patients was 0.61 events/100 patient-years, 120% greater than in a matched patient population without RA. After fully adjusting for comorbid conditions and demographics, the relative risk increase associated with RA dropped to 40%, still significantly higher than in controls (Arthritis Care Res [Hoboken]. 2013 Oct;65[10]:1600-7).
Similarly, Canadian investigators conducted a meta-analysis of 25 studies with VTE data in patients with RA, systemic lupus erythematosus, Sjögren’s syndrome, systemic sclerosis, or inflammatory myositis. This meta-analysis included 10 studies of more than 5.2 million RA patients and nearly 900,000 controls. The conclusion: each of these rheumatic diseases was associated with a VTE rate more than three times higher than in the general population (Arthritis Res Ther. 2014 Sep 25;16[5]:435).
“Patients with RA are at higher risk for VTE than those without RA. It’s unfortunate, and it’s certainly something I don’t think many of us have thought much about before. It’s something we don’t often get to see and something we don’t like to think about,” the rheumatologist observed.
Dr. Genovese admitted to a degree of personal frustration with the current tunnel vision focus on VTEs in JAK inhibitor trials. At the 2017 annual meeting of the American College of Rheumatology he presented the results of the phase 3 SELECT-BEYOND study in which 499 RA patients who had previously failed to respond or were intolerant to biologic therapy were randomized to once daily upadacitinib at 15 or 30 mg or placebo on top of background methotrexate. At week 12, the ACR 20 response rate was 65% for upadacitinib at 15 mg, 56% at 30 mg, and 28% in placebo-treated controls.
“That’s almost a 40% placebo-adjusted response rate. In fact, it’s the highest response I’ve ever seen in a biologic inadequate-responder population. This really looked pretty good, but I don’t think anyone ever took notice. Why not? Because we were all worried about VTE,” he said.
There were in fact a handful of VTEs in upadacitinib-treated patients, Dr. Genovese was quick to note. But he was more impressed by the week 12 ACR 20 responses in patients who had previously failed on three or more biologics: 71% with upadacitinib at 15 mg and 50% at 30 mg, compared with 23% in controls. Moreover, among patients with a baseline history of failure to respond to anti–interleukin-6 therapy, the week 12 ACR 20 rate was 56% with upadacitinib at 15 mg and 58% at 30 mg, versus 20% in controls.
“This looks like a pretty effective drug for patients who’ve failed everything else in our practice,” he commented.
Dr. Genovese reminded his audience that the rheumatology community has a history of overreacting to safety signals in the early days after introduction of new therapies. Examples: tuberculosis with tumor necrosis factor inhibitors, lymphoma with abatacept (Orencia), lymphoma with anti–tumor necrosis factor agents, and cardiovascular events with anti–interleukin-6 inhibition.
“PML [progressive multifocal leukoencephalopathy] is a breathtaking side effect with rituximab [Rituxan], but we’ve gotten over that. We recognize that it’s a potential problem, but we still prescribe rituximab,” the rheumatologist noted. “We’re probably going to need to address the issue of which of our patients are potentially at higher risk for VTE, and maybe we avoid this class in those patients. Like we now do as we look at patients we think are at increased risk for infection, or multiple sclerosis, or TB, we may also need to think of VTE risk.”
But , he argued. There is a pressing unmet need for new therapies for RA with novel mechanisms of action. Only about one-half of patients on contemporary biologic therapies are still on that agent 5 years after initiating therapy.
“Virtually all our patients are partial responders. Everybody gets some benefit. But true remission is achieved by only a minority,” Dr. Genovese said. “The gap between where we are and where we want to be is actually much greater than we often perceive.”
He reported having financial relationships with AbbVie, which is developing upadacitinib, and more than a dozen other medical companies.
EXPERT ANALYSIS FROM RWCS 2018