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Secukinumab’s antipsoriatic effects confirmed in U.S. patient population
and those who up-titrated to 300 mg from the lower approved dose of 150 mg also saw benefits obtained at that level.
Researchers conducted a postmarketing trial of secukinumab in patients at U.S. centers, called CHOICE, after it was approved for psoriasis and PsA in 2015 and 2016 based on trials mainly conducted outside of the United States. The American patients in those studies “had a baseline clinical profile indicating harder-to-treat disease than the total study population, including higher body mass index (BMI), higher tender and swollen joint counts, increased prevalence of enthesitis and dactylitis, and more tumor necrosis factor inhibitor (TNFi) experience,” Tien Q. Nguyen, MD, a dermatologist in private practice in Irvine, Calif., and colleagues wrote in the Journal of Rheumatology.
In order to get a better sense of how secukinumab performs in U.S. patients who have not been treated with biologics, the researchers conducted the multicenter, randomized, double-blind, placebo-controlled, parallel-group, phase 4 CHOICE trial. It recruited patients for about 26 months at 67 U.S. centers during 2016-2018. The 258 patients randomized in the study to 300 mg (n = 103), 150 mg secukinumab (n = 103), or placebo (n = 52) had a mean time since PsA diagnosis of 3.0-3.9 years and all had a mean BMI of greater than 30 kg/m2, with dactylitis present in 48% and enthesitis in 73%. About one-third were taking methotrexate at baseline.
At week 16, patients taking secukinumab 300 mg were about 3.5 times more likely to have 20% improvement in American College of Rheumatology response criteria than with placebo (51.5% vs. 23.1%), whereas the response rate with 150 mg was not significantly different from placebo (36.9%). Rates of achieving ACR50 were significantly greater for both 300- and 150-mg doses versus placebo (28.2% and 24.3% vs. 5.8%), but only 300 mg led to a statistically significant difference in the rate of ACR70 responses, compared with placebo (17.5% vs. 1.9%).
In general, efficacy based on ACR20/50/70 responses and either remission or low disease activity on the Disease Activity in Psoriatic Arthritis index was lower among patients with less than 10 tender joints and less than 10 swollen joints at baseline. Methotrexate use at baseline did not affect ACR20 rates at week 16 in patients taking secukinumab, but the effect of methotrexate on ACR20 rates was noticeable among placebo-treated patients (38.9% vs. 14.7%). Enthesitis appeared to resolve significantly more often among patients on secukinumab, and more patients on secukinumab also had their dactylitis resolve, but the difference was not statistically significant.
Patients with psoriasis affecting more than 3% of their body surface area experienced higher response rates on the Psoriasis Area Severity Index (PASI) for 75%, 90%, and 100% skin lesion clearance than did patients taking placebo.
Patients who switched from 150 mg to 300 mg secukinumab after week 16 in the second treatment period of the trial more often achieved ACR20/50/70 responses by week 52, going from 2.4% to 65.9% of the up-titration subset for ACR20 and from 0% to 34.1% for ACR50 and to 12.2% for ACR70. Patients on placebo who switched also experienced increases in these response rates out to week 52. However, BMI above 30 kg/m2 led to numerically lower ACR50, ACR70, and PASI response rates at week 52.
The researchers noted that the response rates observed in CHOICE were lower than for the pivotal trials used for Food and Drug Administration approval for PsA, which “may have been due to patients in CHOICE having higher disease activity scores at baseline, compared with TNFi-naive patients” in the pivotal trials.
The safety profile of secukinumab appeared to be no different from what has been reported previously. The researchers said that, throughout the 52-week study, the most common adverse events in patients receiving secukinumab were upper respiratory tract infection in about 13% and diarrhea in about 7%. Most adverse events were mild or moderate, with serious adverse events occurring in 9.6% of patients taking secukinumab 300 mg and in 7.8% of patients taking secukinumab 150 mg over the 52 weeks.
“Overall, the findings from CHOICE were consistent with previous studies and demonstrated that secukinumab provides significant and sustained improvements in signs and symptoms of psoriatic arthritis. Our findings suggest that secukinumab 300 mg is safe and efficacious as a first-line biologic treatment for patients with PsA. Further studies will also help determine the optimal dose of secukinumab for treating overweight patients or those with high disease activity at treatment initiation,” the authors wrote.
The study was funded by Novartis, which manufactures secukinumab. Dr. Nguyen and some coauthors reported serving as a consultant, investigator, and/or speaker for numerous pharmaceutical companies, including Novartis.
and those who up-titrated to 300 mg from the lower approved dose of 150 mg also saw benefits obtained at that level.
Researchers conducted a postmarketing trial of secukinumab in patients at U.S. centers, called CHOICE, after it was approved for psoriasis and PsA in 2015 and 2016 based on trials mainly conducted outside of the United States. The American patients in those studies “had a baseline clinical profile indicating harder-to-treat disease than the total study population, including higher body mass index (BMI), higher tender and swollen joint counts, increased prevalence of enthesitis and dactylitis, and more tumor necrosis factor inhibitor (TNFi) experience,” Tien Q. Nguyen, MD, a dermatologist in private practice in Irvine, Calif., and colleagues wrote in the Journal of Rheumatology.
In order to get a better sense of how secukinumab performs in U.S. patients who have not been treated with biologics, the researchers conducted the multicenter, randomized, double-blind, placebo-controlled, parallel-group, phase 4 CHOICE trial. It recruited patients for about 26 months at 67 U.S. centers during 2016-2018. The 258 patients randomized in the study to 300 mg (n = 103), 150 mg secukinumab (n = 103), or placebo (n = 52) had a mean time since PsA diagnosis of 3.0-3.9 years and all had a mean BMI of greater than 30 kg/m2, with dactylitis present in 48% and enthesitis in 73%. About one-third were taking methotrexate at baseline.
At week 16, patients taking secukinumab 300 mg were about 3.5 times more likely to have 20% improvement in American College of Rheumatology response criteria than with placebo (51.5% vs. 23.1%), whereas the response rate with 150 mg was not significantly different from placebo (36.9%). Rates of achieving ACR50 were significantly greater for both 300- and 150-mg doses versus placebo (28.2% and 24.3% vs. 5.8%), but only 300 mg led to a statistically significant difference in the rate of ACR70 responses, compared with placebo (17.5% vs. 1.9%).
In general, efficacy based on ACR20/50/70 responses and either remission or low disease activity on the Disease Activity in Psoriatic Arthritis index was lower among patients with less than 10 tender joints and less than 10 swollen joints at baseline. Methotrexate use at baseline did not affect ACR20 rates at week 16 in patients taking secukinumab, but the effect of methotrexate on ACR20 rates was noticeable among placebo-treated patients (38.9% vs. 14.7%). Enthesitis appeared to resolve significantly more often among patients on secukinumab, and more patients on secukinumab also had their dactylitis resolve, but the difference was not statistically significant.
Patients with psoriasis affecting more than 3% of their body surface area experienced higher response rates on the Psoriasis Area Severity Index (PASI) for 75%, 90%, and 100% skin lesion clearance than did patients taking placebo.
Patients who switched from 150 mg to 300 mg secukinumab after week 16 in the second treatment period of the trial more often achieved ACR20/50/70 responses by week 52, going from 2.4% to 65.9% of the up-titration subset for ACR20 and from 0% to 34.1% for ACR50 and to 12.2% for ACR70. Patients on placebo who switched also experienced increases in these response rates out to week 52. However, BMI above 30 kg/m2 led to numerically lower ACR50, ACR70, and PASI response rates at week 52.
The researchers noted that the response rates observed in CHOICE were lower than for the pivotal trials used for Food and Drug Administration approval for PsA, which “may have been due to patients in CHOICE having higher disease activity scores at baseline, compared with TNFi-naive patients” in the pivotal trials.
The safety profile of secukinumab appeared to be no different from what has been reported previously. The researchers said that, throughout the 52-week study, the most common adverse events in patients receiving secukinumab were upper respiratory tract infection in about 13% and diarrhea in about 7%. Most adverse events were mild or moderate, with serious adverse events occurring in 9.6% of patients taking secukinumab 300 mg and in 7.8% of patients taking secukinumab 150 mg over the 52 weeks.
“Overall, the findings from CHOICE were consistent with previous studies and demonstrated that secukinumab provides significant and sustained improvements in signs and symptoms of psoriatic arthritis. Our findings suggest that secukinumab 300 mg is safe and efficacious as a first-line biologic treatment for patients with PsA. Further studies will also help determine the optimal dose of secukinumab for treating overweight patients or those with high disease activity at treatment initiation,” the authors wrote.
The study was funded by Novartis, which manufactures secukinumab. Dr. Nguyen and some coauthors reported serving as a consultant, investigator, and/or speaker for numerous pharmaceutical companies, including Novartis.
and those who up-titrated to 300 mg from the lower approved dose of 150 mg also saw benefits obtained at that level.
Researchers conducted a postmarketing trial of secukinumab in patients at U.S. centers, called CHOICE, after it was approved for psoriasis and PsA in 2015 and 2016 based on trials mainly conducted outside of the United States. The American patients in those studies “had a baseline clinical profile indicating harder-to-treat disease than the total study population, including higher body mass index (BMI), higher tender and swollen joint counts, increased prevalence of enthesitis and dactylitis, and more tumor necrosis factor inhibitor (TNFi) experience,” Tien Q. Nguyen, MD, a dermatologist in private practice in Irvine, Calif., and colleagues wrote in the Journal of Rheumatology.
In order to get a better sense of how secukinumab performs in U.S. patients who have not been treated with biologics, the researchers conducted the multicenter, randomized, double-blind, placebo-controlled, parallel-group, phase 4 CHOICE trial. It recruited patients for about 26 months at 67 U.S. centers during 2016-2018. The 258 patients randomized in the study to 300 mg (n = 103), 150 mg secukinumab (n = 103), or placebo (n = 52) had a mean time since PsA diagnosis of 3.0-3.9 years and all had a mean BMI of greater than 30 kg/m2, with dactylitis present in 48% and enthesitis in 73%. About one-third were taking methotrexate at baseline.
At week 16, patients taking secukinumab 300 mg were about 3.5 times more likely to have 20% improvement in American College of Rheumatology response criteria than with placebo (51.5% vs. 23.1%), whereas the response rate with 150 mg was not significantly different from placebo (36.9%). Rates of achieving ACR50 were significantly greater for both 300- and 150-mg doses versus placebo (28.2% and 24.3% vs. 5.8%), but only 300 mg led to a statistically significant difference in the rate of ACR70 responses, compared with placebo (17.5% vs. 1.9%).
In general, efficacy based on ACR20/50/70 responses and either remission or low disease activity on the Disease Activity in Psoriatic Arthritis index was lower among patients with less than 10 tender joints and less than 10 swollen joints at baseline. Methotrexate use at baseline did not affect ACR20 rates at week 16 in patients taking secukinumab, but the effect of methotrexate on ACR20 rates was noticeable among placebo-treated patients (38.9% vs. 14.7%). Enthesitis appeared to resolve significantly more often among patients on secukinumab, and more patients on secukinumab also had their dactylitis resolve, but the difference was not statistically significant.
Patients with psoriasis affecting more than 3% of their body surface area experienced higher response rates on the Psoriasis Area Severity Index (PASI) for 75%, 90%, and 100% skin lesion clearance than did patients taking placebo.
Patients who switched from 150 mg to 300 mg secukinumab after week 16 in the second treatment period of the trial more often achieved ACR20/50/70 responses by week 52, going from 2.4% to 65.9% of the up-titration subset for ACR20 and from 0% to 34.1% for ACR50 and to 12.2% for ACR70. Patients on placebo who switched also experienced increases in these response rates out to week 52. However, BMI above 30 kg/m2 led to numerically lower ACR50, ACR70, and PASI response rates at week 52.
The researchers noted that the response rates observed in CHOICE were lower than for the pivotal trials used for Food and Drug Administration approval for PsA, which “may have been due to patients in CHOICE having higher disease activity scores at baseline, compared with TNFi-naive patients” in the pivotal trials.
The safety profile of secukinumab appeared to be no different from what has been reported previously. The researchers said that, throughout the 52-week study, the most common adverse events in patients receiving secukinumab were upper respiratory tract infection in about 13% and diarrhea in about 7%. Most adverse events were mild or moderate, with serious adverse events occurring in 9.6% of patients taking secukinumab 300 mg and in 7.8% of patients taking secukinumab 150 mg over the 52 weeks.
“Overall, the findings from CHOICE were consistent with previous studies and demonstrated that secukinumab provides significant and sustained improvements in signs and symptoms of psoriatic arthritis. Our findings suggest that secukinumab 300 mg is safe and efficacious as a first-line biologic treatment for patients with PsA. Further studies will also help determine the optimal dose of secukinumab for treating overweight patients or those with high disease activity at treatment initiation,” the authors wrote.
The study was funded by Novartis, which manufactures secukinumab. Dr. Nguyen and some coauthors reported serving as a consultant, investigator, and/or speaker for numerous pharmaceutical companies, including Novartis.
FROM THE JOURNAL OF RHEUMATOLOGY
An aspirin a day ... for CRC?
Dear colleagues,
We are all often asked by friends, colleagues, and especially patients how to reduce the risk of getting colorectal cancer. We offer exercise, diet, and smoking cessation as some possible ways to mitigate risk. But what about that wonder drug – the ubiquitous aspirin? The American Gastroenterological Association’s recent clinical practice update suggests that aspirin may be protective in some patients younger than 70 years depending on their cardiovascular and gastrointestinal bleeding risks. If so, should we gastroenterologists be the ones to recommend or even prescribe aspirin? Or are the data just not there yet? We invite two colorectal cancer experts, Dr. Sonia Kupfer and Dr. Jennifer Weiss, to share their perspectives in light of these new recommendations. I invite you to a great debate and look forward to hearing your own thoughts online and by email at ginews@gastro.org.
Gyanprakash A. Ketwaroo, MD, MSc, is assistant professor of medicine at Baylor College of Medicine, Houston. He is an associate editor for GI & Hepatology News.
Not our lane
By Jennifer Weiss, MD, MS
In 2021, the AGA published a clinical practice update on chemoprevention for colorectal neoplasia that advises clinicians to use low-dose aspirin to reduce colorectal cancer (CRC) incidence and mortality in average-risk individuals who are (1) younger than 70 years with a life expectancy of at least 10 years, (2) have at least a 10% 10-year cardiovascular disease (CVD) risk, and (3) are not at high risk for gastrointestinal bleeding.1 As gastroenterologists, we may see average-risk patients only at the time of their screening or surveillance colonoscopies, and I wonder if we should be taking the lead in prescribing/recommending aspirin for CRC chemoprevention in these patients. To answer this question, I will review three main concerns: (1) issues with the overall strength of the evidence on the effectiveness of aspirin to reduce CRC incidence and mortality, (2) determining an individual’s long-term CVD risk and life expectancy may be outside of a gastroenterologist’s purview, and (3) the potential for serious gastrointestinal bleeding is dynamic and requires continual review.
Studies examining the effects of aspirin on CRC incidence and mortality have limitations and mixed results. Many of the randomized controlled trials have primarily been secondary analyses of studies with primary CVD endpoints. When examined individually some studies show no significant reduction in CRC risk such as the Women’s Health Study (at 10 years of follow-up), the Swedish Aspirin Low-Dose Trial, and the UK-TIA Aspirin Trial, while some meta-analyses have shown a decrease in CRC incidence and mortality.2 One reason for this discrepancy may be varying lengths of follow-up across studies. In addition, we do not yet know the optimal aspirin dose or duration of therapy. The protective effect of aspirin on CRC incidence and mortality in average-risk individuals is mostly seen after 10-20 years of follow-up. This is relevant to the first part of the AGA clinical practice update recommendation that refers to individuals with a life expectancy of at least 10 years. The second part of the recommendation includes individuals with a 10-year CVD risk of at least 10%. As gastroenterologists, we may see these patients only two to three times over a 10-20 year period and only for their screening/surveillance colonoscopy. I would argue that we are not in the best position to address changes in life expectancy and 10-year CVD risk status over time and determine if they should start or continue taking aspirin for CRC chemoprevention.
The United States Preventive Services Task Force is also reexamining their previous recommendations for aspirin for primary prevention of cardiovascular disease. The 2016 guidelines recommended initiation of low-dose aspirin for primary prevention of CVD and CRC in adults aged 50-59 years who have a 10% or greater 10-year CVD risk and at least a 10-year life expectancy (Grade B). The current draft recommendations state that aspirin use for the primary prevention of CVD events in adults aged 40-59 years who have a 10% or greater 10-year CVD risk has a small net benefit (Grade C) and that initiating aspirin for the primary prevention of CVD events in adults aged 60 years and older has no net benefit (Grade D). They also state that, based on longer-term follow-up data from the Women’s Health Study and newer trials, the evidence is inadequate that low-dose aspirin use reduces CRC incidence and mortality.3 Because of these moving targets, we may also find ourselves walking back the AGA clinical practice update recommendations in the future.
One main concern for long-term aspirin use is the potential for gastrointestinal bleeding. Participants in more than one of the CVD prevention trials had a significant increase in gastrointestinal bleeding.1,2 While gastrointestinal bleeding falls within our wheelhouse, we are not always privy to a patient’s risk factors for bleeding. For example, patients may receive multiple courses of steroids for arthritis or chronic pulmonary disorders and not take concomitant acid suppression. These risks are dynamic and require continual reassessment as individuals age, new diagnoses are made, and new medications are started or stopped by providers other than their gastroenterologist. If a patient is taking aspirin, regardless of the reason, we need to make sure it is correctly recorded in their medication list, especially if they are obtaining it over the counter. This is one area where we should definitely play a role.
There is a population in which I do recommend aspirin for reduction of CRC chemoprevention – individuals with Lynch syndrome. I believe the data for the protective effects of aspirin on CRC incidence are much stronger for individuals with Lynch syndrome than the average-risk population. The CAPP2 trial was a randomized trial with a two-by-two factorial design where individuals with Lynch syndrome were randomly assigned to aspirin 600 mg/day or aspirin placebo or resistant starch or starch placebo for up to 4 years. The primary endpoint of this trial was development of CRC (unlike the CVD trials referred to earlier in this article). Long-term follow-up of the CAPP2 trial participants found a significantly decreased risk of CRC after 2 years of aspirin use (hazard ratio, 0.56, 95% confidence interval, 0.34-0.91).4 The current CAPP3 trial will answer questions about the effectiveness of lower doses of aspirin (100 mg and 300 mg).
The recommendation for aspirin use for CRC chemoprevention in average-risk individuals depends on multiple factors (life expectancy, determination of CVD risk, and dynamic assessment of gastrointestinal bleeding risk) that are outside the purview of a gastroenterologist who sees the patient only at a screening or surveillance colonoscopy. This is not in our lane. What is in our lane, however, is the recommendation for aspirin use for CRC chemoprevention in select high-risk populations such as individuals with Lynch syndrome.
Dr. Weiss is associate professor in the division of gastroenterology and hepatology and director of the University of Wisconsin Gastroenterology Genetics Clinic at University of Wisconsin School of Medicine and Public Health. She reports receiving research support from Exact Sciences as a site-PI of a multisite trial.
References
1. Liang PS et al. Clin Gastroenterol Hepatol. 2021 Jul;19(7):1327-36. doi: 10.1016/j.cgh.2021.02.014
2. Katona BW and Weiss JM. Gastroenterology. 2020 Jan;158(2):368-88. doi: 10.1053/j.gastro.2019.06.047
3. United States Preventive Services Task Force. “Aspirin Use to Prevent Cardiovascular Disease: Preventive Medication.” Accessed April 5, 2022.
4. Burn J et al. Lancet. 2020 Jun13;395(10240):1855-63. doi: 10.1016/s0140-6736(20)30366-4
Yes, but individualize it
By Sonia S. Kupfer, MD
Colorectal cancer (CRC) is one of the top three causes of cancer and cancer death worldwide with an alarming rise in younger adults. Preventive strategies including screening, chemoprevention, and risk factor modification are important to reduce overall CRC burden. Aspirin, which is cheap and readily available, is supported for CRC chemoprevention by multiple lines of strong evidence. Recent AGA practice guidelines recommend low-dose aspirin chemoprevention in individuals at average CRC risk who are younger than 70 years with a life expectancy of at least 10 years, have a 10-year cardiovascular disease risk of at least 10% and are not at high risk for bleeding.1 This advice diverges from the most recent U.S. Preventive Services Task Force–proposed guidelines2 that reverse the 2016 USPSTF recommendation for aspirin CRC chemoprevention (and primary prevention of cardiovascular disease) based on uncertainty of net benefit over harms, especially in older individuals. In light of conflicting advice, how should we counsel our patients about aspirin use for CRC chemoprevention? In my opinion, we shouldn’t “throw the baby out with the bathwater” and should follow the AGA practice guideline to individualize aspirin chemoprevention based on balancing known benefits and risks.
As reviewed in the AGA practice guidelines1, many, but not all, randomized controlled and observational trials have shown efficacy of aspirin for reduction of CRC mortality, incidence, and adenoma recurrence. Analysis of cardiovascular prevention trials including over 14,000 mostly middle-aged people showed 33% reduction in 20-year cumulative CRC mortality. While a pooled estimate of four trials did not show reduced incidence 0-12 years after aspirin initiation, as noted in the practice guideline, three of these trials did show a 40% reduction between 10 and 19 years, a finding that is in line with results from a 20-year pooled analysis showing 24% reduction in CRC incidence by aspirin. Among Lynch syndrome patients, exposure to high-dose aspirin also significantly reduced CRC incidence in a randomized controlled trial with up to 20 years of follow-up3 highlighting that chemoprotective effects take years to manifest, and long-term follow-up in cancer chemoprevention trials is needed. Studies also have shown reduced adenoma incidence or recurrence by aspirin ranging from 17% to 51% depending on the study population, dose, and adherence. In addition to clinical trials, experimental data have demonstrated protective cellular effects of aspirin on colonic carcinogenesis, though exact mechanisms of this protective effect remain incompletely understood and are active areas of research, including in my lab. Taken together, there is a large body of evidence supporting a protective effect of aspirin on CRC mortality and colorectal neoplasia incidence most evident after 1-2 decades of follow-up.
Not all trials have shown that aspirin is chemoprotective, and, in fact, the ASPREE trial,4 that randomized over 19,000 healthy adults over the age of 70 to 100 mg aspirin or placebo, showed increased cancer mortality when the trial was stopped prematurely after 5 years. Individuals who started aspirin under age 70 appear to have continued chemoprotection as they age5 suggesting that aspirin, if it is tolerated, might not necessarily need to be stopped at a certain age. Notably, the ASPREE trial did not show increased CRC incidence, which begs the question of the biological mechanism underlying increased cancer mortality in trial participants. Beyond the findings of ASPREE, aspirin use is associated with risks of intracranial and gastrointestinal bleeding with estimated odds ratios of 1.29 and 1.59, respectively. The AGA practice guideline acknowledges these risks especially in older adults and recommends initiation of aspirin in individuals under the age of 70 who are expected to live another 10 years without bleeding risks in order to reap the benefits and minimize the risks.
Risk stratification hinges on acceptance and feasibility. Three-quarters of providers, when surveyed, reported aspirin to be a suitable preventive treatment with more favorable views expressed by gastroenterologists and genetics providers, compared with colorectal surgeons.6 In Lynch syndrome, rates of aspirin chemoprevention recommendation by providers in real-world practices ranged from 35% to 67%; my own practice strives to discuss aspirin use with every Lynch patient at every clinic and endoscopy visit. Real-world data for uptake and adherence of aspirin CRC chemoprevention are sparse. Uptake and adherence of aspirin for cancer chemoprevention in clinical trials ranged from 41% to 80% with good adherence, although these findings likely are not generalizable to routine practice. Current blood pressure and cholesterol guidelines for primary prevention include calculation of 10-year cardiovascular risk using automatic calculators in the electronic health record; thus, it should be relatively straightforward to apply this approach for aspirin CRC chemoprevention as well. While calculation of bleeding risk is less well established, there are publicly available calculators that combine cardiovascular and bleeding risk for primary aspirin prevention and such decision aids should be explored for aspirin CRC chemoprevention. However, given the recent recommendation reversal by the USPSTF, I am concerned that recommendation and uptake of aspirin CRC chemoprevention will decline substantially.
In order to reduce CRC burden, we should employ everything in our armamentarium including aspirin chemoprevention. Individualized risk assessment for aspirin chemoprevention, as advised by the AGA practice guideline, will enable the right people to benefit while minimizing risks. Future studies should strengthen the evidence base for aspirin CRC chemoprevention and refine risk stratification, including for younger individuals given the rise in early-onset CRC. The optimal approach to aspirin chemoprevention was best summed up by the foremost expert in the field, Dr. Andy Chan, to the New York Times:7 “we need to think about personalizing who we give aspirin to, and move away from a one-size-fits-all solution”.
Dr. Kupfer is associate professor of medicine, director of the Gastrointestinal Cancer Risk and Prevention Clinic, and codirector of the Comprehensive Cancer Risk and Prevention Clinic at the University of Chicago. She reports no relevant conflicts of interest.
References
1. Liang PS et al. Clin Gastroenterol Hepatol. 2021 Jul;19(7):1327-36.
2. United States Preventive Services Task Force. “Aspirin Use to Prevent Cardiovascular Disease: Preventive Medication.” Accessed April 10, 2022.
3. Burn J et al. Lancet. 2020 Jun 13;395(10240):1855-63.
4. McNeil JJ et al. N Engl J Med. 2018 Oct 18;379(16):1519-28.
5. Guo CG et al. JAMA Oncol. 2021 Mar 1;7(3):428-35.
6. Lloyd KE et al. Prev Med. 2022 Jan;154:106872.
7. Rabin RC. “Aspirin Use to Prevent 1st Heart Attack or Stroke Should Be Curtailed, U.S. Panel Says.” New York Times. Oct. 13, 2021. Accessed April 10, 2022.
Dear colleagues,
We are all often asked by friends, colleagues, and especially patients how to reduce the risk of getting colorectal cancer. We offer exercise, diet, and smoking cessation as some possible ways to mitigate risk. But what about that wonder drug – the ubiquitous aspirin? The American Gastroenterological Association’s recent clinical practice update suggests that aspirin may be protective in some patients younger than 70 years depending on their cardiovascular and gastrointestinal bleeding risks. If so, should we gastroenterologists be the ones to recommend or even prescribe aspirin? Or are the data just not there yet? We invite two colorectal cancer experts, Dr. Sonia Kupfer and Dr. Jennifer Weiss, to share their perspectives in light of these new recommendations. I invite you to a great debate and look forward to hearing your own thoughts online and by email at ginews@gastro.org.
Gyanprakash A. Ketwaroo, MD, MSc, is assistant professor of medicine at Baylor College of Medicine, Houston. He is an associate editor for GI & Hepatology News.
Not our lane
By Jennifer Weiss, MD, MS
In 2021, the AGA published a clinical practice update on chemoprevention for colorectal neoplasia that advises clinicians to use low-dose aspirin to reduce colorectal cancer (CRC) incidence and mortality in average-risk individuals who are (1) younger than 70 years with a life expectancy of at least 10 years, (2) have at least a 10% 10-year cardiovascular disease (CVD) risk, and (3) are not at high risk for gastrointestinal bleeding.1 As gastroenterologists, we may see average-risk patients only at the time of their screening or surveillance colonoscopies, and I wonder if we should be taking the lead in prescribing/recommending aspirin for CRC chemoprevention in these patients. To answer this question, I will review three main concerns: (1) issues with the overall strength of the evidence on the effectiveness of aspirin to reduce CRC incidence and mortality, (2) determining an individual’s long-term CVD risk and life expectancy may be outside of a gastroenterologist’s purview, and (3) the potential for serious gastrointestinal bleeding is dynamic and requires continual review.
Studies examining the effects of aspirin on CRC incidence and mortality have limitations and mixed results. Many of the randomized controlled trials have primarily been secondary analyses of studies with primary CVD endpoints. When examined individually some studies show no significant reduction in CRC risk such as the Women’s Health Study (at 10 years of follow-up), the Swedish Aspirin Low-Dose Trial, and the UK-TIA Aspirin Trial, while some meta-analyses have shown a decrease in CRC incidence and mortality.2 One reason for this discrepancy may be varying lengths of follow-up across studies. In addition, we do not yet know the optimal aspirin dose or duration of therapy. The protective effect of aspirin on CRC incidence and mortality in average-risk individuals is mostly seen after 10-20 years of follow-up. This is relevant to the first part of the AGA clinical practice update recommendation that refers to individuals with a life expectancy of at least 10 years. The second part of the recommendation includes individuals with a 10-year CVD risk of at least 10%. As gastroenterologists, we may see these patients only two to three times over a 10-20 year period and only for their screening/surveillance colonoscopy. I would argue that we are not in the best position to address changes in life expectancy and 10-year CVD risk status over time and determine if they should start or continue taking aspirin for CRC chemoprevention.
The United States Preventive Services Task Force is also reexamining their previous recommendations for aspirin for primary prevention of cardiovascular disease. The 2016 guidelines recommended initiation of low-dose aspirin for primary prevention of CVD and CRC in adults aged 50-59 years who have a 10% or greater 10-year CVD risk and at least a 10-year life expectancy (Grade B). The current draft recommendations state that aspirin use for the primary prevention of CVD events in adults aged 40-59 years who have a 10% or greater 10-year CVD risk has a small net benefit (Grade C) and that initiating aspirin for the primary prevention of CVD events in adults aged 60 years and older has no net benefit (Grade D). They also state that, based on longer-term follow-up data from the Women’s Health Study and newer trials, the evidence is inadequate that low-dose aspirin use reduces CRC incidence and mortality.3 Because of these moving targets, we may also find ourselves walking back the AGA clinical practice update recommendations in the future.
One main concern for long-term aspirin use is the potential for gastrointestinal bleeding. Participants in more than one of the CVD prevention trials had a significant increase in gastrointestinal bleeding.1,2 While gastrointestinal bleeding falls within our wheelhouse, we are not always privy to a patient’s risk factors for bleeding. For example, patients may receive multiple courses of steroids for arthritis or chronic pulmonary disorders and not take concomitant acid suppression. These risks are dynamic and require continual reassessment as individuals age, new diagnoses are made, and new medications are started or stopped by providers other than their gastroenterologist. If a patient is taking aspirin, regardless of the reason, we need to make sure it is correctly recorded in their medication list, especially if they are obtaining it over the counter. This is one area where we should definitely play a role.
There is a population in which I do recommend aspirin for reduction of CRC chemoprevention – individuals with Lynch syndrome. I believe the data for the protective effects of aspirin on CRC incidence are much stronger for individuals with Lynch syndrome than the average-risk population. The CAPP2 trial was a randomized trial with a two-by-two factorial design where individuals with Lynch syndrome were randomly assigned to aspirin 600 mg/day or aspirin placebo or resistant starch or starch placebo for up to 4 years. The primary endpoint of this trial was development of CRC (unlike the CVD trials referred to earlier in this article). Long-term follow-up of the CAPP2 trial participants found a significantly decreased risk of CRC after 2 years of aspirin use (hazard ratio, 0.56, 95% confidence interval, 0.34-0.91).4 The current CAPP3 trial will answer questions about the effectiveness of lower doses of aspirin (100 mg and 300 mg).
The recommendation for aspirin use for CRC chemoprevention in average-risk individuals depends on multiple factors (life expectancy, determination of CVD risk, and dynamic assessment of gastrointestinal bleeding risk) that are outside the purview of a gastroenterologist who sees the patient only at a screening or surveillance colonoscopy. This is not in our lane. What is in our lane, however, is the recommendation for aspirin use for CRC chemoprevention in select high-risk populations such as individuals with Lynch syndrome.
Dr. Weiss is associate professor in the division of gastroenterology and hepatology and director of the University of Wisconsin Gastroenterology Genetics Clinic at University of Wisconsin School of Medicine and Public Health. She reports receiving research support from Exact Sciences as a site-PI of a multisite trial.
References
1. Liang PS et al. Clin Gastroenterol Hepatol. 2021 Jul;19(7):1327-36. doi: 10.1016/j.cgh.2021.02.014
2. Katona BW and Weiss JM. Gastroenterology. 2020 Jan;158(2):368-88. doi: 10.1053/j.gastro.2019.06.047
3. United States Preventive Services Task Force. “Aspirin Use to Prevent Cardiovascular Disease: Preventive Medication.” Accessed April 5, 2022.
4. Burn J et al. Lancet. 2020 Jun13;395(10240):1855-63. doi: 10.1016/s0140-6736(20)30366-4
Yes, but individualize it
By Sonia S. Kupfer, MD
Colorectal cancer (CRC) is one of the top three causes of cancer and cancer death worldwide with an alarming rise in younger adults. Preventive strategies including screening, chemoprevention, and risk factor modification are important to reduce overall CRC burden. Aspirin, which is cheap and readily available, is supported for CRC chemoprevention by multiple lines of strong evidence. Recent AGA practice guidelines recommend low-dose aspirin chemoprevention in individuals at average CRC risk who are younger than 70 years with a life expectancy of at least 10 years, have a 10-year cardiovascular disease risk of at least 10% and are not at high risk for bleeding.1 This advice diverges from the most recent U.S. Preventive Services Task Force–proposed guidelines2 that reverse the 2016 USPSTF recommendation for aspirin CRC chemoprevention (and primary prevention of cardiovascular disease) based on uncertainty of net benefit over harms, especially in older individuals. In light of conflicting advice, how should we counsel our patients about aspirin use for CRC chemoprevention? In my opinion, we shouldn’t “throw the baby out with the bathwater” and should follow the AGA practice guideline to individualize aspirin chemoprevention based on balancing known benefits and risks.
As reviewed in the AGA practice guidelines1, many, but not all, randomized controlled and observational trials have shown efficacy of aspirin for reduction of CRC mortality, incidence, and adenoma recurrence. Analysis of cardiovascular prevention trials including over 14,000 mostly middle-aged people showed 33% reduction in 20-year cumulative CRC mortality. While a pooled estimate of four trials did not show reduced incidence 0-12 years after aspirin initiation, as noted in the practice guideline, three of these trials did show a 40% reduction between 10 and 19 years, a finding that is in line with results from a 20-year pooled analysis showing 24% reduction in CRC incidence by aspirin. Among Lynch syndrome patients, exposure to high-dose aspirin also significantly reduced CRC incidence in a randomized controlled trial with up to 20 years of follow-up3 highlighting that chemoprotective effects take years to manifest, and long-term follow-up in cancer chemoprevention trials is needed. Studies also have shown reduced adenoma incidence or recurrence by aspirin ranging from 17% to 51% depending on the study population, dose, and adherence. In addition to clinical trials, experimental data have demonstrated protective cellular effects of aspirin on colonic carcinogenesis, though exact mechanisms of this protective effect remain incompletely understood and are active areas of research, including in my lab. Taken together, there is a large body of evidence supporting a protective effect of aspirin on CRC mortality and colorectal neoplasia incidence most evident after 1-2 decades of follow-up.
Not all trials have shown that aspirin is chemoprotective, and, in fact, the ASPREE trial,4 that randomized over 19,000 healthy adults over the age of 70 to 100 mg aspirin or placebo, showed increased cancer mortality when the trial was stopped prematurely after 5 years. Individuals who started aspirin under age 70 appear to have continued chemoprotection as they age5 suggesting that aspirin, if it is tolerated, might not necessarily need to be stopped at a certain age. Notably, the ASPREE trial did not show increased CRC incidence, which begs the question of the biological mechanism underlying increased cancer mortality in trial participants. Beyond the findings of ASPREE, aspirin use is associated with risks of intracranial and gastrointestinal bleeding with estimated odds ratios of 1.29 and 1.59, respectively. The AGA practice guideline acknowledges these risks especially in older adults and recommends initiation of aspirin in individuals under the age of 70 who are expected to live another 10 years without bleeding risks in order to reap the benefits and minimize the risks.
Risk stratification hinges on acceptance and feasibility. Three-quarters of providers, when surveyed, reported aspirin to be a suitable preventive treatment with more favorable views expressed by gastroenterologists and genetics providers, compared with colorectal surgeons.6 In Lynch syndrome, rates of aspirin chemoprevention recommendation by providers in real-world practices ranged from 35% to 67%; my own practice strives to discuss aspirin use with every Lynch patient at every clinic and endoscopy visit. Real-world data for uptake and adherence of aspirin CRC chemoprevention are sparse. Uptake and adherence of aspirin for cancer chemoprevention in clinical trials ranged from 41% to 80% with good adherence, although these findings likely are not generalizable to routine practice. Current blood pressure and cholesterol guidelines for primary prevention include calculation of 10-year cardiovascular risk using automatic calculators in the electronic health record; thus, it should be relatively straightforward to apply this approach for aspirin CRC chemoprevention as well. While calculation of bleeding risk is less well established, there are publicly available calculators that combine cardiovascular and bleeding risk for primary aspirin prevention and such decision aids should be explored for aspirin CRC chemoprevention. However, given the recent recommendation reversal by the USPSTF, I am concerned that recommendation and uptake of aspirin CRC chemoprevention will decline substantially.
In order to reduce CRC burden, we should employ everything in our armamentarium including aspirin chemoprevention. Individualized risk assessment for aspirin chemoprevention, as advised by the AGA practice guideline, will enable the right people to benefit while minimizing risks. Future studies should strengthen the evidence base for aspirin CRC chemoprevention and refine risk stratification, including for younger individuals given the rise in early-onset CRC. The optimal approach to aspirin chemoprevention was best summed up by the foremost expert in the field, Dr. Andy Chan, to the New York Times:7 “we need to think about personalizing who we give aspirin to, and move away from a one-size-fits-all solution”.
Dr. Kupfer is associate professor of medicine, director of the Gastrointestinal Cancer Risk and Prevention Clinic, and codirector of the Comprehensive Cancer Risk and Prevention Clinic at the University of Chicago. She reports no relevant conflicts of interest.
References
1. Liang PS et al. Clin Gastroenterol Hepatol. 2021 Jul;19(7):1327-36.
2. United States Preventive Services Task Force. “Aspirin Use to Prevent Cardiovascular Disease: Preventive Medication.” Accessed April 10, 2022.
3. Burn J et al. Lancet. 2020 Jun 13;395(10240):1855-63.
4. McNeil JJ et al. N Engl J Med. 2018 Oct 18;379(16):1519-28.
5. Guo CG et al. JAMA Oncol. 2021 Mar 1;7(3):428-35.
6. Lloyd KE et al. Prev Med. 2022 Jan;154:106872.
7. Rabin RC. “Aspirin Use to Prevent 1st Heart Attack or Stroke Should Be Curtailed, U.S. Panel Says.” New York Times. Oct. 13, 2021. Accessed April 10, 2022.
Dear colleagues,
We are all often asked by friends, colleagues, and especially patients how to reduce the risk of getting colorectal cancer. We offer exercise, diet, and smoking cessation as some possible ways to mitigate risk. But what about that wonder drug – the ubiquitous aspirin? The American Gastroenterological Association’s recent clinical practice update suggests that aspirin may be protective in some patients younger than 70 years depending on their cardiovascular and gastrointestinal bleeding risks. If so, should we gastroenterologists be the ones to recommend or even prescribe aspirin? Or are the data just not there yet? We invite two colorectal cancer experts, Dr. Sonia Kupfer and Dr. Jennifer Weiss, to share their perspectives in light of these new recommendations. I invite you to a great debate and look forward to hearing your own thoughts online and by email at ginews@gastro.org.
Gyanprakash A. Ketwaroo, MD, MSc, is assistant professor of medicine at Baylor College of Medicine, Houston. He is an associate editor for GI & Hepatology News.
Not our lane
By Jennifer Weiss, MD, MS
In 2021, the AGA published a clinical practice update on chemoprevention for colorectal neoplasia that advises clinicians to use low-dose aspirin to reduce colorectal cancer (CRC) incidence and mortality in average-risk individuals who are (1) younger than 70 years with a life expectancy of at least 10 years, (2) have at least a 10% 10-year cardiovascular disease (CVD) risk, and (3) are not at high risk for gastrointestinal bleeding.1 As gastroenterologists, we may see average-risk patients only at the time of their screening or surveillance colonoscopies, and I wonder if we should be taking the lead in prescribing/recommending aspirin for CRC chemoprevention in these patients. To answer this question, I will review three main concerns: (1) issues with the overall strength of the evidence on the effectiveness of aspirin to reduce CRC incidence and mortality, (2) determining an individual’s long-term CVD risk and life expectancy may be outside of a gastroenterologist’s purview, and (3) the potential for serious gastrointestinal bleeding is dynamic and requires continual review.
Studies examining the effects of aspirin on CRC incidence and mortality have limitations and mixed results. Many of the randomized controlled trials have primarily been secondary analyses of studies with primary CVD endpoints. When examined individually some studies show no significant reduction in CRC risk such as the Women’s Health Study (at 10 years of follow-up), the Swedish Aspirin Low-Dose Trial, and the UK-TIA Aspirin Trial, while some meta-analyses have shown a decrease in CRC incidence and mortality.2 One reason for this discrepancy may be varying lengths of follow-up across studies. In addition, we do not yet know the optimal aspirin dose or duration of therapy. The protective effect of aspirin on CRC incidence and mortality in average-risk individuals is mostly seen after 10-20 years of follow-up. This is relevant to the first part of the AGA clinical practice update recommendation that refers to individuals with a life expectancy of at least 10 years. The second part of the recommendation includes individuals with a 10-year CVD risk of at least 10%. As gastroenterologists, we may see these patients only two to three times over a 10-20 year period and only for their screening/surveillance colonoscopy. I would argue that we are not in the best position to address changes in life expectancy and 10-year CVD risk status over time and determine if they should start or continue taking aspirin for CRC chemoprevention.
The United States Preventive Services Task Force is also reexamining their previous recommendations for aspirin for primary prevention of cardiovascular disease. The 2016 guidelines recommended initiation of low-dose aspirin for primary prevention of CVD and CRC in adults aged 50-59 years who have a 10% or greater 10-year CVD risk and at least a 10-year life expectancy (Grade B). The current draft recommendations state that aspirin use for the primary prevention of CVD events in adults aged 40-59 years who have a 10% or greater 10-year CVD risk has a small net benefit (Grade C) and that initiating aspirin for the primary prevention of CVD events in adults aged 60 years and older has no net benefit (Grade D). They also state that, based on longer-term follow-up data from the Women’s Health Study and newer trials, the evidence is inadequate that low-dose aspirin use reduces CRC incidence and mortality.3 Because of these moving targets, we may also find ourselves walking back the AGA clinical practice update recommendations in the future.
One main concern for long-term aspirin use is the potential for gastrointestinal bleeding. Participants in more than one of the CVD prevention trials had a significant increase in gastrointestinal bleeding.1,2 While gastrointestinal bleeding falls within our wheelhouse, we are not always privy to a patient’s risk factors for bleeding. For example, patients may receive multiple courses of steroids for arthritis or chronic pulmonary disorders and not take concomitant acid suppression. These risks are dynamic and require continual reassessment as individuals age, new diagnoses are made, and new medications are started or stopped by providers other than their gastroenterologist. If a patient is taking aspirin, regardless of the reason, we need to make sure it is correctly recorded in their medication list, especially if they are obtaining it over the counter. This is one area where we should definitely play a role.
There is a population in which I do recommend aspirin for reduction of CRC chemoprevention – individuals with Lynch syndrome. I believe the data for the protective effects of aspirin on CRC incidence are much stronger for individuals with Lynch syndrome than the average-risk population. The CAPP2 trial was a randomized trial with a two-by-two factorial design where individuals with Lynch syndrome were randomly assigned to aspirin 600 mg/day or aspirin placebo or resistant starch or starch placebo for up to 4 years. The primary endpoint of this trial was development of CRC (unlike the CVD trials referred to earlier in this article). Long-term follow-up of the CAPP2 trial participants found a significantly decreased risk of CRC after 2 years of aspirin use (hazard ratio, 0.56, 95% confidence interval, 0.34-0.91).4 The current CAPP3 trial will answer questions about the effectiveness of lower doses of aspirin (100 mg and 300 mg).
The recommendation for aspirin use for CRC chemoprevention in average-risk individuals depends on multiple factors (life expectancy, determination of CVD risk, and dynamic assessment of gastrointestinal bleeding risk) that are outside the purview of a gastroenterologist who sees the patient only at a screening or surveillance colonoscopy. This is not in our lane. What is in our lane, however, is the recommendation for aspirin use for CRC chemoprevention in select high-risk populations such as individuals with Lynch syndrome.
Dr. Weiss is associate professor in the division of gastroenterology and hepatology and director of the University of Wisconsin Gastroenterology Genetics Clinic at University of Wisconsin School of Medicine and Public Health. She reports receiving research support from Exact Sciences as a site-PI of a multisite trial.
References
1. Liang PS et al. Clin Gastroenterol Hepatol. 2021 Jul;19(7):1327-36. doi: 10.1016/j.cgh.2021.02.014
2. Katona BW and Weiss JM. Gastroenterology. 2020 Jan;158(2):368-88. doi: 10.1053/j.gastro.2019.06.047
3. United States Preventive Services Task Force. “Aspirin Use to Prevent Cardiovascular Disease: Preventive Medication.” Accessed April 5, 2022.
4. Burn J et al. Lancet. 2020 Jun13;395(10240):1855-63. doi: 10.1016/s0140-6736(20)30366-4
Yes, but individualize it
By Sonia S. Kupfer, MD
Colorectal cancer (CRC) is one of the top three causes of cancer and cancer death worldwide with an alarming rise in younger adults. Preventive strategies including screening, chemoprevention, and risk factor modification are important to reduce overall CRC burden. Aspirin, which is cheap and readily available, is supported for CRC chemoprevention by multiple lines of strong evidence. Recent AGA practice guidelines recommend low-dose aspirin chemoprevention in individuals at average CRC risk who are younger than 70 years with a life expectancy of at least 10 years, have a 10-year cardiovascular disease risk of at least 10% and are not at high risk for bleeding.1 This advice diverges from the most recent U.S. Preventive Services Task Force–proposed guidelines2 that reverse the 2016 USPSTF recommendation for aspirin CRC chemoprevention (and primary prevention of cardiovascular disease) based on uncertainty of net benefit over harms, especially in older individuals. In light of conflicting advice, how should we counsel our patients about aspirin use for CRC chemoprevention? In my opinion, we shouldn’t “throw the baby out with the bathwater” and should follow the AGA practice guideline to individualize aspirin chemoprevention based on balancing known benefits and risks.
As reviewed in the AGA practice guidelines1, many, but not all, randomized controlled and observational trials have shown efficacy of aspirin for reduction of CRC mortality, incidence, and adenoma recurrence. Analysis of cardiovascular prevention trials including over 14,000 mostly middle-aged people showed 33% reduction in 20-year cumulative CRC mortality. While a pooled estimate of four trials did not show reduced incidence 0-12 years after aspirin initiation, as noted in the practice guideline, three of these trials did show a 40% reduction between 10 and 19 years, a finding that is in line with results from a 20-year pooled analysis showing 24% reduction in CRC incidence by aspirin. Among Lynch syndrome patients, exposure to high-dose aspirin also significantly reduced CRC incidence in a randomized controlled trial with up to 20 years of follow-up3 highlighting that chemoprotective effects take years to manifest, and long-term follow-up in cancer chemoprevention trials is needed. Studies also have shown reduced adenoma incidence or recurrence by aspirin ranging from 17% to 51% depending on the study population, dose, and adherence. In addition to clinical trials, experimental data have demonstrated protective cellular effects of aspirin on colonic carcinogenesis, though exact mechanisms of this protective effect remain incompletely understood and are active areas of research, including in my lab. Taken together, there is a large body of evidence supporting a protective effect of aspirin on CRC mortality and colorectal neoplasia incidence most evident after 1-2 decades of follow-up.
Not all trials have shown that aspirin is chemoprotective, and, in fact, the ASPREE trial,4 that randomized over 19,000 healthy adults over the age of 70 to 100 mg aspirin or placebo, showed increased cancer mortality when the trial was stopped prematurely after 5 years. Individuals who started aspirin under age 70 appear to have continued chemoprotection as they age5 suggesting that aspirin, if it is tolerated, might not necessarily need to be stopped at a certain age. Notably, the ASPREE trial did not show increased CRC incidence, which begs the question of the biological mechanism underlying increased cancer mortality in trial participants. Beyond the findings of ASPREE, aspirin use is associated with risks of intracranial and gastrointestinal bleeding with estimated odds ratios of 1.29 and 1.59, respectively. The AGA practice guideline acknowledges these risks especially in older adults and recommends initiation of aspirin in individuals under the age of 70 who are expected to live another 10 years without bleeding risks in order to reap the benefits and minimize the risks.
Risk stratification hinges on acceptance and feasibility. Three-quarters of providers, when surveyed, reported aspirin to be a suitable preventive treatment with more favorable views expressed by gastroenterologists and genetics providers, compared with colorectal surgeons.6 In Lynch syndrome, rates of aspirin chemoprevention recommendation by providers in real-world practices ranged from 35% to 67%; my own practice strives to discuss aspirin use with every Lynch patient at every clinic and endoscopy visit. Real-world data for uptake and adherence of aspirin CRC chemoprevention are sparse. Uptake and adherence of aspirin for cancer chemoprevention in clinical trials ranged from 41% to 80% with good adherence, although these findings likely are not generalizable to routine practice. Current blood pressure and cholesterol guidelines for primary prevention include calculation of 10-year cardiovascular risk using automatic calculators in the electronic health record; thus, it should be relatively straightforward to apply this approach for aspirin CRC chemoprevention as well. While calculation of bleeding risk is less well established, there are publicly available calculators that combine cardiovascular and bleeding risk for primary aspirin prevention and such decision aids should be explored for aspirin CRC chemoprevention. However, given the recent recommendation reversal by the USPSTF, I am concerned that recommendation and uptake of aspirin CRC chemoprevention will decline substantially.
In order to reduce CRC burden, we should employ everything in our armamentarium including aspirin chemoprevention. Individualized risk assessment for aspirin chemoprevention, as advised by the AGA practice guideline, will enable the right people to benefit while minimizing risks. Future studies should strengthen the evidence base for aspirin CRC chemoprevention and refine risk stratification, including for younger individuals given the rise in early-onset CRC. The optimal approach to aspirin chemoprevention was best summed up by the foremost expert in the field, Dr. Andy Chan, to the New York Times:7 “we need to think about personalizing who we give aspirin to, and move away from a one-size-fits-all solution”.
Dr. Kupfer is associate professor of medicine, director of the Gastrointestinal Cancer Risk and Prevention Clinic, and codirector of the Comprehensive Cancer Risk and Prevention Clinic at the University of Chicago. She reports no relevant conflicts of interest.
References
1. Liang PS et al. Clin Gastroenterol Hepatol. 2021 Jul;19(7):1327-36.
2. United States Preventive Services Task Force. “Aspirin Use to Prevent Cardiovascular Disease: Preventive Medication.” Accessed April 10, 2022.
3. Burn J et al. Lancet. 2020 Jun 13;395(10240):1855-63.
4. McNeil JJ et al. N Engl J Med. 2018 Oct 18;379(16):1519-28.
5. Guo CG et al. JAMA Oncol. 2021 Mar 1;7(3):428-35.
6. Lloyd KE et al. Prev Med. 2022 Jan;154:106872.
7. Rabin RC. “Aspirin Use to Prevent 1st Heart Attack or Stroke Should Be Curtailed, U.S. Panel Says.” New York Times. Oct. 13, 2021. Accessed April 10, 2022.
OARSI sets sights on classifying early-stage knee OA
An expert task force convened by the Osteoarthritis Research Society International (OARSI) has started the process of consolidating classification criteria for early-stage knee osteoarthritis (OA).
“Early-stage knee OA classification criteria, we believe are critically required,” Gillian Hawker, MD, MSc, said at the OARSI 2022 World Congress.
Dr. Hawker, who is the chair of the Task Force Steering Committee, noted that classification criteria are needed for several reasons, such as “to advance OA therapeutics and [the] earlier identification of people with knee OA who can benefit from existing treatments.”
Moreover, they are needed so that people with knee OA can “be poised and ready to receive available therapies once we develop them,” said Dr. Hawker, professor of medicine at the University of Toronto and a senior clinician-scientist in the Women’s College Research Institute at Women’s College Hospital in Toronto.
Reasoning for looking at early OA
“Osteoarthritis is a very serious disease with a growing population burden,” Dr. Hawker reminded delegates at the congress. Yet despite “amazing advances” in the understanding of the pathophysiology of disease and several potential druggable targets being identified, “we still have no safe and effective interventions to prevent or slow the progression of the disease.”
“Why have all the DMOADs [disease-modifying osteoarthritis drugs] failed?” she questioned.
One hypothesis is that it’s down to the heterogeneity of OA. “We’ve been plugging people with different kinds or phenotypes of OA into the same clinical trials, and we need to better match OA phenotypes with appropriate treatment,” Dr. Hawker said.
Also, “structural changes on imaging, and the symptoms that characterize the disease of function, pain, stiffness, etc., are not super well correlated. It may be that any attempts at structure modification alone won’t adequately improve clinical symptoms.”
Perhaps most importantly, however, “we’re treating people way too late in the course of their disease,” Dr. Hawker said. “When we keep putting people with Kellgren and Lawrence [grade] 2 or 3 into clinical trials, it may be that we there’s nothing that we’re going to be able to do that’s really going to make a difference.”
Why just knee OA?
The reason for looking at early-stage OA specifically is that current knee OA classification criteria were developed nearly 40 years ago and were looking at a later stage of disease, mainly differentiating OA from other types of inflammatory arthritis, notably rheumatoid arthritis (RA).
The aim of the OARSI Early OA Task Force is thus to develop, refine, and validate classification criteria that will not only help identify people with early-stage OA who can then be entered into clinical trials of new therapies but also define a population that can be used in preclinical and prognostic work.
“The task force decided to start with early-stage knee OA due to the highest burden and the focus of most clinical trials,” steering committee member Martin Englund, MD, PhD, observed during the discussion.
“When we see how that goes, we may consider early hip OA,” said Dr. Englund, of Lund University and Skåne University Hospital in Sweden.
Dr. Hawker added that the task force felt that lumping hip and knee OA together would complicate matters because they thought that the classification criteria will likely look very different from each other.
“But the good news is we think that if we can identify early knee OA, we will likely also identify people with at least hand OA,” she said.
Building on previous work
The OARSI Task Force initiative will build on the early OA work by Stefan Lohmander, MD, PhD, and Frank Luyten, MD, PhD, who were part of a consensus panel that proposed draft classification criteria a few years ago. Those criteria, derived from a consensus workshop that had included basic scientists, physician-scientists, rheumatologists, orthopedic surgeons, and physiotherapists, identified three main areas of importance: Patient symptoms such as pain and function, the presence of crepitus or tender joints on clinical examination, and having a low Kellgren and Lawrence grade (0 or 1).
Dr. Lohmander remains heavily involved, heading up the advisory committee, with many other ad hoc committees likely to be set up during the project.
“We had over 70 people in the OARSI community volunteering to participate in some way, shape, or form,” Dr. Hawker said. All will be needed, she said, as there will be a lot of work to do. The starting point is people with undifferentiated knee symptoms, identifying the factors that increase or decrease the likelihood of having early-stage OA. Once a population has been found, the outcomes for prevention need to be defined.
A systematic search of the available literature has started and full-text review of more than 200 papers is in progress. The challenge ahead is to define what the ‘anchor question’ will be. That is, what question should be asked in order to determine whether a patient fulfills the criteria?
Dr. Hawker noted that when the American College of Rheumatology developed the RA classification criteria, the anchor question had been around whether methotrexate should be prescribed.
“We don’t have a ‘methotrexate’ in osteoarthritis, and it’s pretty low risk to start weight management or physical activity or even prescribe a topical anti-inflammatory,” she said. “So, we’re still trying to work out exactly how we create our anchor.”
It’s likely that the anchor question will be based on expert opinion rather than hard data. Perhaps it will focus on the chances that a patient’s symptoms will become persistent with loss of function or that they will develop established OA. It could perhaps be around the initiation of a novel DMOAD, if one proved effective enough to be used.
“We have many, many, many, questions!” Dr. Hawker said. One of the important ones is deciding what exactly should be prevented. Symptoms? Structural damage?
“I think a combination of symptoms and loss of function are probably what we want to prevent. But again, we’re going to have to define that very clearly. This is going to take us quite a bit of time.”
It’s likely to be a two-stage process: “First we define what is early stage OA, and then we identify those who are at the highest risk of rapid progression so that we can target those individuals for clinical trials.”
Dr. Hawker and Dr. Englund had no conflicts of interest to disclose.
An expert task force convened by the Osteoarthritis Research Society International (OARSI) has started the process of consolidating classification criteria for early-stage knee osteoarthritis (OA).
“Early-stage knee OA classification criteria, we believe are critically required,” Gillian Hawker, MD, MSc, said at the OARSI 2022 World Congress.
Dr. Hawker, who is the chair of the Task Force Steering Committee, noted that classification criteria are needed for several reasons, such as “to advance OA therapeutics and [the] earlier identification of people with knee OA who can benefit from existing treatments.”
Moreover, they are needed so that people with knee OA can “be poised and ready to receive available therapies once we develop them,” said Dr. Hawker, professor of medicine at the University of Toronto and a senior clinician-scientist in the Women’s College Research Institute at Women’s College Hospital in Toronto.
Reasoning for looking at early OA
“Osteoarthritis is a very serious disease with a growing population burden,” Dr. Hawker reminded delegates at the congress. Yet despite “amazing advances” in the understanding of the pathophysiology of disease and several potential druggable targets being identified, “we still have no safe and effective interventions to prevent or slow the progression of the disease.”
“Why have all the DMOADs [disease-modifying osteoarthritis drugs] failed?” she questioned.
One hypothesis is that it’s down to the heterogeneity of OA. “We’ve been plugging people with different kinds or phenotypes of OA into the same clinical trials, and we need to better match OA phenotypes with appropriate treatment,” Dr. Hawker said.
Also, “structural changes on imaging, and the symptoms that characterize the disease of function, pain, stiffness, etc., are not super well correlated. It may be that any attempts at structure modification alone won’t adequately improve clinical symptoms.”
Perhaps most importantly, however, “we’re treating people way too late in the course of their disease,” Dr. Hawker said. “When we keep putting people with Kellgren and Lawrence [grade] 2 or 3 into clinical trials, it may be that we there’s nothing that we’re going to be able to do that’s really going to make a difference.”
Why just knee OA?
The reason for looking at early-stage OA specifically is that current knee OA classification criteria were developed nearly 40 years ago and were looking at a later stage of disease, mainly differentiating OA from other types of inflammatory arthritis, notably rheumatoid arthritis (RA).
The aim of the OARSI Early OA Task Force is thus to develop, refine, and validate classification criteria that will not only help identify people with early-stage OA who can then be entered into clinical trials of new therapies but also define a population that can be used in preclinical and prognostic work.
“The task force decided to start with early-stage knee OA due to the highest burden and the focus of most clinical trials,” steering committee member Martin Englund, MD, PhD, observed during the discussion.
“When we see how that goes, we may consider early hip OA,” said Dr. Englund, of Lund University and Skåne University Hospital in Sweden.
Dr. Hawker added that the task force felt that lumping hip and knee OA together would complicate matters because they thought that the classification criteria will likely look very different from each other.
“But the good news is we think that if we can identify early knee OA, we will likely also identify people with at least hand OA,” she said.
Building on previous work
The OARSI Task Force initiative will build on the early OA work by Stefan Lohmander, MD, PhD, and Frank Luyten, MD, PhD, who were part of a consensus panel that proposed draft classification criteria a few years ago. Those criteria, derived from a consensus workshop that had included basic scientists, physician-scientists, rheumatologists, orthopedic surgeons, and physiotherapists, identified three main areas of importance: Patient symptoms such as pain and function, the presence of crepitus or tender joints on clinical examination, and having a low Kellgren and Lawrence grade (0 or 1).
Dr. Lohmander remains heavily involved, heading up the advisory committee, with many other ad hoc committees likely to be set up during the project.
“We had over 70 people in the OARSI community volunteering to participate in some way, shape, or form,” Dr. Hawker said. All will be needed, she said, as there will be a lot of work to do. The starting point is people with undifferentiated knee symptoms, identifying the factors that increase or decrease the likelihood of having early-stage OA. Once a population has been found, the outcomes for prevention need to be defined.
A systematic search of the available literature has started and full-text review of more than 200 papers is in progress. The challenge ahead is to define what the ‘anchor question’ will be. That is, what question should be asked in order to determine whether a patient fulfills the criteria?
Dr. Hawker noted that when the American College of Rheumatology developed the RA classification criteria, the anchor question had been around whether methotrexate should be prescribed.
“We don’t have a ‘methotrexate’ in osteoarthritis, and it’s pretty low risk to start weight management or physical activity or even prescribe a topical anti-inflammatory,” she said. “So, we’re still trying to work out exactly how we create our anchor.”
It’s likely that the anchor question will be based on expert opinion rather than hard data. Perhaps it will focus on the chances that a patient’s symptoms will become persistent with loss of function or that they will develop established OA. It could perhaps be around the initiation of a novel DMOAD, if one proved effective enough to be used.
“We have many, many, many, questions!” Dr. Hawker said. One of the important ones is deciding what exactly should be prevented. Symptoms? Structural damage?
“I think a combination of symptoms and loss of function are probably what we want to prevent. But again, we’re going to have to define that very clearly. This is going to take us quite a bit of time.”
It’s likely to be a two-stage process: “First we define what is early stage OA, and then we identify those who are at the highest risk of rapid progression so that we can target those individuals for clinical trials.”
Dr. Hawker and Dr. Englund had no conflicts of interest to disclose.
An expert task force convened by the Osteoarthritis Research Society International (OARSI) has started the process of consolidating classification criteria for early-stage knee osteoarthritis (OA).
“Early-stage knee OA classification criteria, we believe are critically required,” Gillian Hawker, MD, MSc, said at the OARSI 2022 World Congress.
Dr. Hawker, who is the chair of the Task Force Steering Committee, noted that classification criteria are needed for several reasons, such as “to advance OA therapeutics and [the] earlier identification of people with knee OA who can benefit from existing treatments.”
Moreover, they are needed so that people with knee OA can “be poised and ready to receive available therapies once we develop them,” said Dr. Hawker, professor of medicine at the University of Toronto and a senior clinician-scientist in the Women’s College Research Institute at Women’s College Hospital in Toronto.
Reasoning for looking at early OA
“Osteoarthritis is a very serious disease with a growing population burden,” Dr. Hawker reminded delegates at the congress. Yet despite “amazing advances” in the understanding of the pathophysiology of disease and several potential druggable targets being identified, “we still have no safe and effective interventions to prevent or slow the progression of the disease.”
“Why have all the DMOADs [disease-modifying osteoarthritis drugs] failed?” she questioned.
One hypothesis is that it’s down to the heterogeneity of OA. “We’ve been plugging people with different kinds or phenotypes of OA into the same clinical trials, and we need to better match OA phenotypes with appropriate treatment,” Dr. Hawker said.
Also, “structural changes on imaging, and the symptoms that characterize the disease of function, pain, stiffness, etc., are not super well correlated. It may be that any attempts at structure modification alone won’t adequately improve clinical symptoms.”
Perhaps most importantly, however, “we’re treating people way too late in the course of their disease,” Dr. Hawker said. “When we keep putting people with Kellgren and Lawrence [grade] 2 or 3 into clinical trials, it may be that we there’s nothing that we’re going to be able to do that’s really going to make a difference.”
Why just knee OA?
The reason for looking at early-stage OA specifically is that current knee OA classification criteria were developed nearly 40 years ago and were looking at a later stage of disease, mainly differentiating OA from other types of inflammatory arthritis, notably rheumatoid arthritis (RA).
The aim of the OARSI Early OA Task Force is thus to develop, refine, and validate classification criteria that will not only help identify people with early-stage OA who can then be entered into clinical trials of new therapies but also define a population that can be used in preclinical and prognostic work.
“The task force decided to start with early-stage knee OA due to the highest burden and the focus of most clinical trials,” steering committee member Martin Englund, MD, PhD, observed during the discussion.
“When we see how that goes, we may consider early hip OA,” said Dr. Englund, of Lund University and Skåne University Hospital in Sweden.
Dr. Hawker added that the task force felt that lumping hip and knee OA together would complicate matters because they thought that the classification criteria will likely look very different from each other.
“But the good news is we think that if we can identify early knee OA, we will likely also identify people with at least hand OA,” she said.
Building on previous work
The OARSI Task Force initiative will build on the early OA work by Stefan Lohmander, MD, PhD, and Frank Luyten, MD, PhD, who were part of a consensus panel that proposed draft classification criteria a few years ago. Those criteria, derived from a consensus workshop that had included basic scientists, physician-scientists, rheumatologists, orthopedic surgeons, and physiotherapists, identified three main areas of importance: Patient symptoms such as pain and function, the presence of crepitus or tender joints on clinical examination, and having a low Kellgren and Lawrence grade (0 or 1).
Dr. Lohmander remains heavily involved, heading up the advisory committee, with many other ad hoc committees likely to be set up during the project.
“We had over 70 people in the OARSI community volunteering to participate in some way, shape, or form,” Dr. Hawker said. All will be needed, she said, as there will be a lot of work to do. The starting point is people with undifferentiated knee symptoms, identifying the factors that increase or decrease the likelihood of having early-stage OA. Once a population has been found, the outcomes for prevention need to be defined.
A systematic search of the available literature has started and full-text review of more than 200 papers is in progress. The challenge ahead is to define what the ‘anchor question’ will be. That is, what question should be asked in order to determine whether a patient fulfills the criteria?
Dr. Hawker noted that when the American College of Rheumatology developed the RA classification criteria, the anchor question had been around whether methotrexate should be prescribed.
“We don’t have a ‘methotrexate’ in osteoarthritis, and it’s pretty low risk to start weight management or physical activity or even prescribe a topical anti-inflammatory,” she said. “So, we’re still trying to work out exactly how we create our anchor.”
It’s likely that the anchor question will be based on expert opinion rather than hard data. Perhaps it will focus on the chances that a patient’s symptoms will become persistent with loss of function or that they will develop established OA. It could perhaps be around the initiation of a novel DMOAD, if one proved effective enough to be used.
“We have many, many, many, questions!” Dr. Hawker said. One of the important ones is deciding what exactly should be prevented. Symptoms? Structural damage?
“I think a combination of symptoms and loss of function are probably what we want to prevent. But again, we’re going to have to define that very clearly. This is going to take us quite a bit of time.”
It’s likely to be a two-stage process: “First we define what is early stage OA, and then we identify those who are at the highest risk of rapid progression so that we can target those individuals for clinical trials.”
Dr. Hawker and Dr. Englund had no conflicts of interest to disclose.
FROM OARSI 2022
AGAF applications now open
AGA is proud to formally recognize its exemplary members whose accomplishments and contributions demonstrate a deep commitment to gastroenterology through the AGA Fellows Program. Those in clinical practice, education, or research (basic or clinical) are encouraged to apply today.
Longstanding members who apply and meet the program criteria are granted the distinguished honor of AGA Fellowship and receive the following:
- The privilege of using the designation “AGAF” in professional activities.
- An official certificate and pin denoting your status.
- International acknowledgment at Digestive Disease Week® (DDW).
- A listing on the AGA website alongside esteemed peers.
- A prewritten, fill-in press release, and a digital badge to inform others of your accomplishment.
Learn more
Apply for consideration and gain recognition worldwide for your commitment to the field. The deadline is Aug. 24, 2022.
If you have any questions, contact AGA Member Relations at member@gastro.org or 301-941-2651.
AGA is proud to formally recognize its exemplary members whose accomplishments and contributions demonstrate a deep commitment to gastroenterology through the AGA Fellows Program. Those in clinical practice, education, or research (basic or clinical) are encouraged to apply today.
Longstanding members who apply and meet the program criteria are granted the distinguished honor of AGA Fellowship and receive the following:
- The privilege of using the designation “AGAF” in professional activities.
- An official certificate and pin denoting your status.
- International acknowledgment at Digestive Disease Week® (DDW).
- A listing on the AGA website alongside esteemed peers.
- A prewritten, fill-in press release, and a digital badge to inform others of your accomplishment.
Learn more
Apply for consideration and gain recognition worldwide for your commitment to the field. The deadline is Aug. 24, 2022.
If you have any questions, contact AGA Member Relations at member@gastro.org or 301-941-2651.
AGA is proud to formally recognize its exemplary members whose accomplishments and contributions demonstrate a deep commitment to gastroenterology through the AGA Fellows Program. Those in clinical practice, education, or research (basic or clinical) are encouraged to apply today.
Longstanding members who apply and meet the program criteria are granted the distinguished honor of AGA Fellowship and receive the following:
- The privilege of using the designation “AGAF” in professional activities.
- An official certificate and pin denoting your status.
- International acknowledgment at Digestive Disease Week® (DDW).
- A listing on the AGA website alongside esteemed peers.
- A prewritten, fill-in press release, and a digital badge to inform others of your accomplishment.
Learn more
Apply for consideration and gain recognition worldwide for your commitment to the field. The deadline is Aug. 24, 2022.
If you have any questions, contact AGA Member Relations at member@gastro.org or 301-941-2651.
Puzzles
Doctors love puzzles, they say. Especially neurologists.
The detective work on a case is part of the job’s appeal. Taking clues from the history, exam, and tests to formulate a diagnosis, then a treatment plan.
But I’m not talking about that.
As I’ve written before, I’ve tried hard to divorce myself from the news. In times where the world seems to have gone mad, I just don’t want to know what’s going on. I focus on my family, my job, and the weather forecast.
But, inevitably, I need something to do. At some point I run out of notes to type, tests to review, emails to answer, and bills to pay. I used to read the news, but now I don’t do that anymore. I even avoid my favorite satire sites, like Onion and Beaverton, because they just reflect the real news (I still read the Weekly World News, which has no relationship to reality, or pretty much anything, whatsoever).
So now, when I’m done with the day’s work, I shut down the computer (which isn’t easy after 25 years of habitual surfing) and sit down with a jigsaw puzzle. I haven’t done that since I was a resident.
It usually takes me 2-3 weeks to do one (500-1,000 pieces) in the 30 minutes or so I spend on it each evening. There’s solace in the quiet, methodical process of carefully looking for matching pieces, trying a few, the brief glee at getting a fit, and then moving to the next piece.
I know I can do this on my iPad, but it’s different with real pieces. Lifting up a piece and examining it for matching shapes and colors, sorting through the tray, wondering if I made a mistake somewhere. The cardboard doesn’t light up to let me know I got it right.
Inevitably, the mind wanders as I work on them. Sometimes back to a puzzle at the office, sometimes to my doing the same puzzle (I’ve had them for a while) at my parents’ house in my teens, sometimes to my kids away at college, or a book I once read.
But that’s the point. It’s almost a form of meditation. Focusing on each piece as my mind moves in other directions. It’s actually more relaxing than I thought, and a welcome escape from the day.
And, like other seemingly unrelated tasks (such as Leo Szilard waiting for a traffic light to change, albeit on a lesser scale), sometimes it brings me an answer I’ve been searching for. A light bulb will go on for a patient case I’ve been turning over for a few days. When that happens I grab my phone and email the thought to myself at work.
It puts my mind in neutral at the end of the day. When I finally go to bed I’m less focused on things that can keep me awake at night.
Though occasionally I do dream of puzzles.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
Doctors love puzzles, they say. Especially neurologists.
The detective work on a case is part of the job’s appeal. Taking clues from the history, exam, and tests to formulate a diagnosis, then a treatment plan.
But I’m not talking about that.
As I’ve written before, I’ve tried hard to divorce myself from the news. In times where the world seems to have gone mad, I just don’t want to know what’s going on. I focus on my family, my job, and the weather forecast.
But, inevitably, I need something to do. At some point I run out of notes to type, tests to review, emails to answer, and bills to pay. I used to read the news, but now I don’t do that anymore. I even avoid my favorite satire sites, like Onion and Beaverton, because they just reflect the real news (I still read the Weekly World News, which has no relationship to reality, or pretty much anything, whatsoever).
So now, when I’m done with the day’s work, I shut down the computer (which isn’t easy after 25 years of habitual surfing) and sit down with a jigsaw puzzle. I haven’t done that since I was a resident.
It usually takes me 2-3 weeks to do one (500-1,000 pieces) in the 30 minutes or so I spend on it each evening. There’s solace in the quiet, methodical process of carefully looking for matching pieces, trying a few, the brief glee at getting a fit, and then moving to the next piece.
I know I can do this on my iPad, but it’s different with real pieces. Lifting up a piece and examining it for matching shapes and colors, sorting through the tray, wondering if I made a mistake somewhere. The cardboard doesn’t light up to let me know I got it right.
Inevitably, the mind wanders as I work on them. Sometimes back to a puzzle at the office, sometimes to my doing the same puzzle (I’ve had them for a while) at my parents’ house in my teens, sometimes to my kids away at college, or a book I once read.
But that’s the point. It’s almost a form of meditation. Focusing on each piece as my mind moves in other directions. It’s actually more relaxing than I thought, and a welcome escape from the day.
And, like other seemingly unrelated tasks (such as Leo Szilard waiting for a traffic light to change, albeit on a lesser scale), sometimes it brings me an answer I’ve been searching for. A light bulb will go on for a patient case I’ve been turning over for a few days. When that happens I grab my phone and email the thought to myself at work.
It puts my mind in neutral at the end of the day. When I finally go to bed I’m less focused on things that can keep me awake at night.
Though occasionally I do dream of puzzles.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
Doctors love puzzles, they say. Especially neurologists.
The detective work on a case is part of the job’s appeal. Taking clues from the history, exam, and tests to formulate a diagnosis, then a treatment plan.
But I’m not talking about that.
As I’ve written before, I’ve tried hard to divorce myself from the news. In times where the world seems to have gone mad, I just don’t want to know what’s going on. I focus on my family, my job, and the weather forecast.
But, inevitably, I need something to do. At some point I run out of notes to type, tests to review, emails to answer, and bills to pay. I used to read the news, but now I don’t do that anymore. I even avoid my favorite satire sites, like Onion and Beaverton, because they just reflect the real news (I still read the Weekly World News, which has no relationship to reality, or pretty much anything, whatsoever).
So now, when I’m done with the day’s work, I shut down the computer (which isn’t easy after 25 years of habitual surfing) and sit down with a jigsaw puzzle. I haven’t done that since I was a resident.
It usually takes me 2-3 weeks to do one (500-1,000 pieces) in the 30 minutes or so I spend on it each evening. There’s solace in the quiet, methodical process of carefully looking for matching pieces, trying a few, the brief glee at getting a fit, and then moving to the next piece.
I know I can do this on my iPad, but it’s different with real pieces. Lifting up a piece and examining it for matching shapes and colors, sorting through the tray, wondering if I made a mistake somewhere. The cardboard doesn’t light up to let me know I got it right.
Inevitably, the mind wanders as I work on them. Sometimes back to a puzzle at the office, sometimes to my doing the same puzzle (I’ve had them for a while) at my parents’ house in my teens, sometimes to my kids away at college, or a book I once read.
But that’s the point. It’s almost a form of meditation. Focusing on each piece as my mind moves in other directions. It’s actually more relaxing than I thought, and a welcome escape from the day.
And, like other seemingly unrelated tasks (such as Leo Szilard waiting for a traffic light to change, albeit on a lesser scale), sometimes it brings me an answer I’ve been searching for. A light bulb will go on for a patient case I’ve been turning over for a few days. When that happens I grab my phone and email the thought to myself at work.
It puts my mind in neutral at the end of the day. When I finally go to bed I’m less focused on things that can keep me awake at night.
Though occasionally I do dream of puzzles.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
Interview with Dr. John Inadomi: Inside the DDW® 2022 AGA Presidential Plenary
The 2022 AGA Presidential Plenary at Digestive Disease Week® (DDW) is designed to highlight timely and high-impact research as it pertains to AGA and the global gastroenterology community. This year’s plenary will feature a series of invited speaker talks on the ways to integrate diversity and inclusion into the field of gastroenterology and hepatology.
AGA President John M. Inadomi, MD, AGAF, will present his address titled “Don’t Talk – Act: The Relevance of DEI to Gastroenterologists and Hepatologists and the Imperative for Action.” Read our Q&A with Dr. Inadomi below for details on what you can expect from the plenary.
Why did you want to focus on issues around diversity, equity, and inclusion in the presidential plenary?
Most obvious is the pandemic and the social issues the pandemic has amplified have made these issues a primary concern for AGA. The pandemic forced us to reexamine ourselves and to not assume everything we’ve done in the past should be done in the future. The diversity of AGA and AGA leadership is not where we want it to be. I want to use the presidential plenary as a platform to discuss race, especially, which is only one part of DEI. I can provide perspective as an Asian American experiencing a resurgence in racism and I want to involve nationally known experts like Monica Webb Hooper who’ve done research on this and have fully formed ideas on how to frame the questions and talk about action items that we, as a society, should adopt. The time of reflection and awareness has passed, the time of simply providing awareness is past. Society needs to adopt action items to address and combat racism.
Later in the plenary, I’m pleased to be joined by Dr. Byron Cryer and Dr. Sandra Quezada who will talk about how they created/developed the AGA Equity Project and their work to implement it.
What do you want attendees to take home from these various talks?
We hear a lot of talk about DEI, I hear a lot about awareness, a lot of talk about education. I asked the presidential plenary speakers to move beyond that to provide action items that AGA and its members can implement to reduce disparities in health outcomes. I hope that we will be able to measure these outcomes and see improvement over time coming out of the interventions proposed during this session.
Why did you choose disparities in CRC, liver disease, and IBD specifically?
I feel like these are core parts of gastroenterology and hepatology. So much of the disparities we see in colon cancer are a microcosm of the disparities that exist across the spectrum of GI and liver disease. They illustrate the problems with access and utilization. Disparities in CRC outcomes are exacerbated by the pandemic. I chose liver disease because it’s another area where racial disparities exist and are exacerbated by the pandemic. All three are core services provided by gastroenterologists and hepatologists and represent areas where racism has caused disparities in outcomes. Greatly magnified by the pandemic.
Why is the Association of Black Gastroenterologists and Hepatologists (ABGH) important?
It’s important for me to listen to people who are the target of racism and hear how they want AGA to address their concerns. I want a better understanding of why ABGH was formed and why now. I want to hear what they hope to achieve and how they believe the AGA can help.
The full AGA Presidential Plenary line-up
We hope you’ll join us for the AGA Presidential Plenary, taking place Monday, May 23, at 10 a.m. PT during DDW. In addition to Dr. Inadomi’s keynote address, presentations will include:
- AGA Julius Friedenwald Recognition of Timothy Wang
- AGA Equity Project: Accomplishments and What Lies Ahead
- The Genesis and Goals of the Association of Black Gastroenterologists and Hepatologists (ABGH)
- What We Need to Overcome Racial and Ethnic Barriers to Engage in Clinical Trials
- Reducing Disparities in Colorectal Cancer
- Reducing Disparities in Liver Disease
- Reducing Disparities in IBD
The 2022 AGA Presidential Plenary at Digestive Disease Week® (DDW) is designed to highlight timely and high-impact research as it pertains to AGA and the global gastroenterology community. This year’s plenary will feature a series of invited speaker talks on the ways to integrate diversity and inclusion into the field of gastroenterology and hepatology.
AGA President John M. Inadomi, MD, AGAF, will present his address titled “Don’t Talk – Act: The Relevance of DEI to Gastroenterologists and Hepatologists and the Imperative for Action.” Read our Q&A with Dr. Inadomi below for details on what you can expect from the plenary.
Why did you want to focus on issues around diversity, equity, and inclusion in the presidential plenary?
Most obvious is the pandemic and the social issues the pandemic has amplified have made these issues a primary concern for AGA. The pandemic forced us to reexamine ourselves and to not assume everything we’ve done in the past should be done in the future. The diversity of AGA and AGA leadership is not where we want it to be. I want to use the presidential plenary as a platform to discuss race, especially, which is only one part of DEI. I can provide perspective as an Asian American experiencing a resurgence in racism and I want to involve nationally known experts like Monica Webb Hooper who’ve done research on this and have fully formed ideas on how to frame the questions and talk about action items that we, as a society, should adopt. The time of reflection and awareness has passed, the time of simply providing awareness is past. Society needs to adopt action items to address and combat racism.
Later in the plenary, I’m pleased to be joined by Dr. Byron Cryer and Dr. Sandra Quezada who will talk about how they created/developed the AGA Equity Project and their work to implement it.
What do you want attendees to take home from these various talks?
We hear a lot of talk about DEI, I hear a lot about awareness, a lot of talk about education. I asked the presidential plenary speakers to move beyond that to provide action items that AGA and its members can implement to reduce disparities in health outcomes. I hope that we will be able to measure these outcomes and see improvement over time coming out of the interventions proposed during this session.
Why did you choose disparities in CRC, liver disease, and IBD specifically?
I feel like these are core parts of gastroenterology and hepatology. So much of the disparities we see in colon cancer are a microcosm of the disparities that exist across the spectrum of GI and liver disease. They illustrate the problems with access and utilization. Disparities in CRC outcomes are exacerbated by the pandemic. I chose liver disease because it’s another area where racial disparities exist and are exacerbated by the pandemic. All three are core services provided by gastroenterologists and hepatologists and represent areas where racism has caused disparities in outcomes. Greatly magnified by the pandemic.
Why is the Association of Black Gastroenterologists and Hepatologists (ABGH) important?
It’s important for me to listen to people who are the target of racism and hear how they want AGA to address their concerns. I want a better understanding of why ABGH was formed and why now. I want to hear what they hope to achieve and how they believe the AGA can help.
The full AGA Presidential Plenary line-up
We hope you’ll join us for the AGA Presidential Plenary, taking place Monday, May 23, at 10 a.m. PT during DDW. In addition to Dr. Inadomi’s keynote address, presentations will include:
- AGA Julius Friedenwald Recognition of Timothy Wang
- AGA Equity Project: Accomplishments and What Lies Ahead
- The Genesis and Goals of the Association of Black Gastroenterologists and Hepatologists (ABGH)
- What We Need to Overcome Racial and Ethnic Barriers to Engage in Clinical Trials
- Reducing Disparities in Colorectal Cancer
- Reducing Disparities in Liver Disease
- Reducing Disparities in IBD
The 2022 AGA Presidential Plenary at Digestive Disease Week® (DDW) is designed to highlight timely and high-impact research as it pertains to AGA and the global gastroenterology community. This year’s plenary will feature a series of invited speaker talks on the ways to integrate diversity and inclusion into the field of gastroenterology and hepatology.
AGA President John M. Inadomi, MD, AGAF, will present his address titled “Don’t Talk – Act: The Relevance of DEI to Gastroenterologists and Hepatologists and the Imperative for Action.” Read our Q&A with Dr. Inadomi below for details on what you can expect from the plenary.
Why did you want to focus on issues around diversity, equity, and inclusion in the presidential plenary?
Most obvious is the pandemic and the social issues the pandemic has amplified have made these issues a primary concern for AGA. The pandemic forced us to reexamine ourselves and to not assume everything we’ve done in the past should be done in the future. The diversity of AGA and AGA leadership is not where we want it to be. I want to use the presidential plenary as a platform to discuss race, especially, which is only one part of DEI. I can provide perspective as an Asian American experiencing a resurgence in racism and I want to involve nationally known experts like Monica Webb Hooper who’ve done research on this and have fully formed ideas on how to frame the questions and talk about action items that we, as a society, should adopt. The time of reflection and awareness has passed, the time of simply providing awareness is past. Society needs to adopt action items to address and combat racism.
Later in the plenary, I’m pleased to be joined by Dr. Byron Cryer and Dr. Sandra Quezada who will talk about how they created/developed the AGA Equity Project and their work to implement it.
What do you want attendees to take home from these various talks?
We hear a lot of talk about DEI, I hear a lot about awareness, a lot of talk about education. I asked the presidential plenary speakers to move beyond that to provide action items that AGA and its members can implement to reduce disparities in health outcomes. I hope that we will be able to measure these outcomes and see improvement over time coming out of the interventions proposed during this session.
Why did you choose disparities in CRC, liver disease, and IBD specifically?
I feel like these are core parts of gastroenterology and hepatology. So much of the disparities we see in colon cancer are a microcosm of the disparities that exist across the spectrum of GI and liver disease. They illustrate the problems with access and utilization. Disparities in CRC outcomes are exacerbated by the pandemic. I chose liver disease because it’s another area where racial disparities exist and are exacerbated by the pandemic. All three are core services provided by gastroenterologists and hepatologists and represent areas where racism has caused disparities in outcomes. Greatly magnified by the pandemic.
Why is the Association of Black Gastroenterologists and Hepatologists (ABGH) important?
It’s important for me to listen to people who are the target of racism and hear how they want AGA to address their concerns. I want a better understanding of why ABGH was formed and why now. I want to hear what they hope to achieve and how they believe the AGA can help.
The full AGA Presidential Plenary line-up
We hope you’ll join us for the AGA Presidential Plenary, taking place Monday, May 23, at 10 a.m. PT during DDW. In addition to Dr. Inadomi’s keynote address, presentations will include:
- AGA Julius Friedenwald Recognition of Timothy Wang
- AGA Equity Project: Accomplishments and What Lies Ahead
- The Genesis and Goals of the Association of Black Gastroenterologists and Hepatologists (ABGH)
- What We Need to Overcome Racial and Ethnic Barriers to Engage in Clinical Trials
- Reducing Disparities in Colorectal Cancer
- Reducing Disparities in Liver Disease
- Reducing Disparities in IBD
Remember the AGA Research Foundation in your will or living trust
You have a will, so you can rest easy, right? Not necessarily. If your will is outdated, it can cause more harm than good. Even though it can provide for some contingencies, an old will can’t cover every change that may have occurred since it was first drawn.
What if all you had to do to ensure that the AGA Research Foundation can have an impact for years to come is to write a simple sentence? Sound impossible?
The AGA Research Foundation provides a key source of funding at a critical juncture in a young investigator’s career. Securing the future of the talented investigators we serve really is as simple as one sentence.
Including the AGA Research Foundation in your will is a popular gift to give because it is:
- Affordable. The actual giving of your gift occurs after your lifetime, so your current income is not affected.
- Flexible. Until your will goes into effect, you are free to alter your plans or change your mind.
- Versatile. You can give a specific item, a set amount of money, or a percentage of your estate. You can also make your gift contingent upon certain events.
We hope you’ll consider including a gift to the AGA Research Foundation in your will or living trust. It’s simple – just a few sentences in your will or trust are all that is needed. The official bequest language for the AGA Research Foundation is: “I, [name], of [city, state, ZIP], give, devise, and bequeath to the AGA Research Foundation [written amount or percentage of the estate or description of property] for its unrestricted use and purpose.”
Join others in donating to the AGA Research Foundation and help fill the funding gap and protect the next generation of investigators. Contact us for more information at foundation@gastro.org or visit http://gastro.planmylegacy.org.
You have a will, so you can rest easy, right? Not necessarily. If your will is outdated, it can cause more harm than good. Even though it can provide for some contingencies, an old will can’t cover every change that may have occurred since it was first drawn.
What if all you had to do to ensure that the AGA Research Foundation can have an impact for years to come is to write a simple sentence? Sound impossible?
The AGA Research Foundation provides a key source of funding at a critical juncture in a young investigator’s career. Securing the future of the talented investigators we serve really is as simple as one sentence.
Including the AGA Research Foundation in your will is a popular gift to give because it is:
- Affordable. The actual giving of your gift occurs after your lifetime, so your current income is not affected.
- Flexible. Until your will goes into effect, you are free to alter your plans or change your mind.
- Versatile. You can give a specific item, a set amount of money, or a percentage of your estate. You can also make your gift contingent upon certain events.
We hope you’ll consider including a gift to the AGA Research Foundation in your will or living trust. It’s simple – just a few sentences in your will or trust are all that is needed. The official bequest language for the AGA Research Foundation is: “I, [name], of [city, state, ZIP], give, devise, and bequeath to the AGA Research Foundation [written amount or percentage of the estate or description of property] for its unrestricted use and purpose.”
Join others in donating to the AGA Research Foundation and help fill the funding gap and protect the next generation of investigators. Contact us for more information at foundation@gastro.org or visit http://gastro.planmylegacy.org.
You have a will, so you can rest easy, right? Not necessarily. If your will is outdated, it can cause more harm than good. Even though it can provide for some contingencies, an old will can’t cover every change that may have occurred since it was first drawn.
What if all you had to do to ensure that the AGA Research Foundation can have an impact for years to come is to write a simple sentence? Sound impossible?
The AGA Research Foundation provides a key source of funding at a critical juncture in a young investigator’s career. Securing the future of the talented investigators we serve really is as simple as one sentence.
Including the AGA Research Foundation in your will is a popular gift to give because it is:
- Affordable. The actual giving of your gift occurs after your lifetime, so your current income is not affected.
- Flexible. Until your will goes into effect, you are free to alter your plans or change your mind.
- Versatile. You can give a specific item, a set amount of money, or a percentage of your estate. You can also make your gift contingent upon certain events.
We hope you’ll consider including a gift to the AGA Research Foundation in your will or living trust. It’s simple – just a few sentences in your will or trust are all that is needed. The official bequest language for the AGA Research Foundation is: “I, [name], of [city, state, ZIP], give, devise, and bequeath to the AGA Research Foundation [written amount or percentage of the estate or description of property] for its unrestricted use and purpose.”
Join others in donating to the AGA Research Foundation and help fill the funding gap and protect the next generation of investigators. Contact us for more information at foundation@gastro.org or visit http://gastro.planmylegacy.org.
Fluorescence optical imaging holds potential for detecting early signs of PsA
Key clinical point: This follow-up comparison of fluorescence optical imaging (FOI) with musculoskeletal ultrasound (MSUS) showed that FOI can be considered a useful screening tool for the early diagnosis of psoriatic arthritis (PsA).
Major finding: Patients diagnosed with PsA after the baseline evaluation had a higher prevalence of joints with pathological enhancement in FOI during follow-up (P = .046), notably in phase 2 FOI (P = .037). Similar to MSUS (area under the curve [AUC] 0.77), detecting newly affected joints by FOI (phase 2 in PrimaVista Mode; AUC 0.78) was positively linked with the shift of diagnosis from suspected to confirmed PsA.
Study details: In this follow-up study of 30 patients with psoriasis who had tender or swollen joints, the FOI of both the hands and the grayscale/power Doppler MSUS of the clinically dominant hand were compared.
Disclosures: This study was supported by the BMBF, German Ministry for Education and Research. The authors declared no conflict of interests.
Source: Buttner J et al. Follow-up comparison of fluorescence optical imaging with musculoskeletal ultrasound for early detection of psoriatic arthritis. Front Med. 2022;9:845545 (Mar 18). Doi: 10.3389/fmed.2022.845545
Key clinical point: This follow-up comparison of fluorescence optical imaging (FOI) with musculoskeletal ultrasound (MSUS) showed that FOI can be considered a useful screening tool for the early diagnosis of psoriatic arthritis (PsA).
Major finding: Patients diagnosed with PsA after the baseline evaluation had a higher prevalence of joints with pathological enhancement in FOI during follow-up (P = .046), notably in phase 2 FOI (P = .037). Similar to MSUS (area under the curve [AUC] 0.77), detecting newly affected joints by FOI (phase 2 in PrimaVista Mode; AUC 0.78) was positively linked with the shift of diagnosis from suspected to confirmed PsA.
Study details: In this follow-up study of 30 patients with psoriasis who had tender or swollen joints, the FOI of both the hands and the grayscale/power Doppler MSUS of the clinically dominant hand were compared.
Disclosures: This study was supported by the BMBF, German Ministry for Education and Research. The authors declared no conflict of interests.
Source: Buttner J et al. Follow-up comparison of fluorescence optical imaging with musculoskeletal ultrasound for early detection of psoriatic arthritis. Front Med. 2022;9:845545 (Mar 18). Doi: 10.3389/fmed.2022.845545
Key clinical point: This follow-up comparison of fluorescence optical imaging (FOI) with musculoskeletal ultrasound (MSUS) showed that FOI can be considered a useful screening tool for the early diagnosis of psoriatic arthritis (PsA).
Major finding: Patients diagnosed with PsA after the baseline evaluation had a higher prevalence of joints with pathological enhancement in FOI during follow-up (P = .046), notably in phase 2 FOI (P = .037). Similar to MSUS (area under the curve [AUC] 0.77), detecting newly affected joints by FOI (phase 2 in PrimaVista Mode; AUC 0.78) was positively linked with the shift of diagnosis from suspected to confirmed PsA.
Study details: In this follow-up study of 30 patients with psoriasis who had tender or swollen joints, the FOI of both the hands and the grayscale/power Doppler MSUS of the clinically dominant hand were compared.
Disclosures: This study was supported by the BMBF, German Ministry for Education and Research. The authors declared no conflict of interests.
Source: Buttner J et al. Follow-up comparison of fluorescence optical imaging with musculoskeletal ultrasound for early detection of psoriatic arthritis. Front Med. 2022;9:845545 (Mar 18). Doi: 10.3389/fmed.2022.845545
Guselkumab reduces collagen degradation biomarker levels associated with active PsA
Key clinical point: Serum levels of certain collagen degradation biomarkers were elevated in patients with psoriatic arthritis (PsA) vs. healthy controls (HC) and could be effectively lowered with guselkumab.
Major finding: Baseline serum concentrations of collagen degradation biomarkers C1M, C3M, C4M, and C6M were ≥1.25-times higher in patients with PsA vs. HC (adjusted P < .05). At week 24, 100 mg guselkumab every 4 weeks vs. placebo significantly reduced C1M, C3M, and C4M levels, whereas guselkumab 100 mg every 8 weeks vs. placebo significantly reduced C3M, C4M, and C6M levels (all adjusted P < .05), with improvements maintained up to week 52 (all adjusted P ≤ .0001).
Study details: Findings are from an exploratory analysis of the phase 3 DISCOVER 2 study that included 260 patients with active PsA and an inadequate response to standard and 76 HC.
Disclosures: This study was supported by Janssen Research & Development, LLC. Eight authors declared being employees of Janssen and owned stock in Johnson & Johnson, the parent company for Janssen. The other authors reported ties with several sources, including Janssen.
Source: Schett G et al. collagen turnover biomarkers associate with active psoriatic arthritis and decrease with guselkumab treatment in a phase 3 clinical trial (DISCOVER-2). Rheumatol Ther. 2022 (Mar 30). Doi: 10.1007/s40744-022-00444-x
Key clinical point: Serum levels of certain collagen degradation biomarkers were elevated in patients with psoriatic arthritis (PsA) vs. healthy controls (HC) and could be effectively lowered with guselkumab.
Major finding: Baseline serum concentrations of collagen degradation biomarkers C1M, C3M, C4M, and C6M were ≥1.25-times higher in patients with PsA vs. HC (adjusted P < .05). At week 24, 100 mg guselkumab every 4 weeks vs. placebo significantly reduced C1M, C3M, and C4M levels, whereas guselkumab 100 mg every 8 weeks vs. placebo significantly reduced C3M, C4M, and C6M levels (all adjusted P < .05), with improvements maintained up to week 52 (all adjusted P ≤ .0001).
Study details: Findings are from an exploratory analysis of the phase 3 DISCOVER 2 study that included 260 patients with active PsA and an inadequate response to standard and 76 HC.
Disclosures: This study was supported by Janssen Research & Development, LLC. Eight authors declared being employees of Janssen and owned stock in Johnson & Johnson, the parent company for Janssen. The other authors reported ties with several sources, including Janssen.
Source: Schett G et al. collagen turnover biomarkers associate with active psoriatic arthritis and decrease with guselkumab treatment in a phase 3 clinical trial (DISCOVER-2). Rheumatol Ther. 2022 (Mar 30). Doi: 10.1007/s40744-022-00444-x
Key clinical point: Serum levels of certain collagen degradation biomarkers were elevated in patients with psoriatic arthritis (PsA) vs. healthy controls (HC) and could be effectively lowered with guselkumab.
Major finding: Baseline serum concentrations of collagen degradation biomarkers C1M, C3M, C4M, and C6M were ≥1.25-times higher in patients with PsA vs. HC (adjusted P < .05). At week 24, 100 mg guselkumab every 4 weeks vs. placebo significantly reduced C1M, C3M, and C4M levels, whereas guselkumab 100 mg every 8 weeks vs. placebo significantly reduced C3M, C4M, and C6M levels (all adjusted P < .05), with improvements maintained up to week 52 (all adjusted P ≤ .0001).
Study details: Findings are from an exploratory analysis of the phase 3 DISCOVER 2 study that included 260 patients with active PsA and an inadequate response to standard and 76 HC.
Disclosures: This study was supported by Janssen Research & Development, LLC. Eight authors declared being employees of Janssen and owned stock in Johnson & Johnson, the parent company for Janssen. The other authors reported ties with several sources, including Janssen.
Source: Schett G et al. collagen turnover biomarkers associate with active psoriatic arthritis and decrease with guselkumab treatment in a phase 3 clinical trial (DISCOVER-2). Rheumatol Ther. 2022 (Mar 30). Doi: 10.1007/s40744-022-00444-x
Large integrated safety analysis reinforces known safety profile of ixekizumab in PsA
Key clinical point: Ixekizumab demonstrated an overall consistent safety and tolerability profile with no unexpected/new adverse events (AE) in patients with psoriatic arthritis (PsA) and up to 3 years of exposure to ixekizumab.
Major finding: Treatment-emergent (mostly mild/moderate) and serious AE occurred in 80.7% and 9.6% of patients, respectively. The most common infections were nasopharyngitis, upper respiratory tract infection, bronchitis, and sinusitis, with frequency for serious events being ≤2%. The exposure-adjusted incidence rate for treatment-emergent AE reduced from 87 in the first year to 67.3 in the third year of ixekizumab exposure and was <2 for malignancies, inflammatory bowel disease, depression, and major adverse cerebrocardiovascular events.
Study details: This integrated safety analysis of four phase 3 trials included 1401 patients with active PsA and a cumulative ixekizumab exposure of 2247.7 patient-years.
Disclosures: This study was supported by Eli Lilly and Company. Five authors declared being employees and shareholders of Eli Lilly and Company and other authors reported ties with various sources, including Eli Lilly.
Source: Deodhar AA et al. Safety of ixekizumab in patients with psoriatic arthritis: data from four clinical trials with over 2000 patient-years of exposure. Ann Rheum Dis. 2022 (Apr 7). Doi: 10.1136/annrheumdis-2021-222027
Key clinical point: Ixekizumab demonstrated an overall consistent safety and tolerability profile with no unexpected/new adverse events (AE) in patients with psoriatic arthritis (PsA) and up to 3 years of exposure to ixekizumab.
Major finding: Treatment-emergent (mostly mild/moderate) and serious AE occurred in 80.7% and 9.6% of patients, respectively. The most common infections were nasopharyngitis, upper respiratory tract infection, bronchitis, and sinusitis, with frequency for serious events being ≤2%. The exposure-adjusted incidence rate for treatment-emergent AE reduced from 87 in the first year to 67.3 in the third year of ixekizumab exposure and was <2 for malignancies, inflammatory bowel disease, depression, and major adverse cerebrocardiovascular events.
Study details: This integrated safety analysis of four phase 3 trials included 1401 patients with active PsA and a cumulative ixekizumab exposure of 2247.7 patient-years.
Disclosures: This study was supported by Eli Lilly and Company. Five authors declared being employees and shareholders of Eli Lilly and Company and other authors reported ties with various sources, including Eli Lilly.
Source: Deodhar AA et al. Safety of ixekizumab in patients with psoriatic arthritis: data from four clinical trials with over 2000 patient-years of exposure. Ann Rheum Dis. 2022 (Apr 7). Doi: 10.1136/annrheumdis-2021-222027
Key clinical point: Ixekizumab demonstrated an overall consistent safety and tolerability profile with no unexpected/new adverse events (AE) in patients with psoriatic arthritis (PsA) and up to 3 years of exposure to ixekizumab.
Major finding: Treatment-emergent (mostly mild/moderate) and serious AE occurred in 80.7% and 9.6% of patients, respectively. The most common infections were nasopharyngitis, upper respiratory tract infection, bronchitis, and sinusitis, with frequency for serious events being ≤2%. The exposure-adjusted incidence rate for treatment-emergent AE reduced from 87 in the first year to 67.3 in the third year of ixekizumab exposure and was <2 for malignancies, inflammatory bowel disease, depression, and major adverse cerebrocardiovascular events.
Study details: This integrated safety analysis of four phase 3 trials included 1401 patients with active PsA and a cumulative ixekizumab exposure of 2247.7 patient-years.
Disclosures: This study was supported by Eli Lilly and Company. Five authors declared being employees and shareholders of Eli Lilly and Company and other authors reported ties with various sources, including Eli Lilly.
Source: Deodhar AA et al. Safety of ixekizumab in patients with psoriatic arthritis: data from four clinical trials with over 2000 patient-years of exposure. Ann Rheum Dis. 2022 (Apr 7). Doi: 10.1136/annrheumdis-2021-222027