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Angiotensin Receptor Blockers May Lead to Worse Outcomes in Celiac Disease
PHILADELPHIA — , according to a study presented at the American College of Gastroenterology (ACG) 2024 Annual Scientific Meeting.
The association may be related to the similar pathophysiology between ARB-associated enteropathy and celiac disease, though additional research is needed.
“Based on our findings, people should take caution when prescribing angiotensin receptor blockers to people with celiac disease,” said lead author Isabel Hujoel, MD, clinical assistant professor of gastroenterology and clinic director of the Celiac Disease Center at the University of Washington, Seattle.
“When we see someone with nonresponsive celiac disease, meaning persistent symptoms despite a gluten-free diet, I do think we should review their medication list, and if they’re on an ARB, we should consider a trial off those medications to see if they respond,” she said. “A primary care provider may choose other hypertensives as well.”
Hujoel and co-author Margaux Hujoel, PhD, a postdoctoral research fellow at Brigham and Women’s Hospital, Boston; Broad Institute, Cambridge; and Harvard Medical School, Boston, analyzed data from the National Institutes of Health’s All of Us, a large publicly available US longitudinal dataset.
The researchers conducted a survival analysis of time-to-first event after celiac disease diagnosis, allowing patients to have a time-dependent covariate of ARB use. They looked at outcomes such as iron deficiency, diarrhea, abdominal pain, vitamin deficiency, vitamin D deficiency, malabsorption, low hemoglobin, and weight loss.
The analysis included 1849 patients with celiac disease, including 1460 women and 389 men, with a median age of nearly 50 years at diagnosis. While the vast majority of patients (nearly 1600) didn’t take an ARB, 120 started one before celiac disease diagnosis and 142 started one after diagnosis.
Overall, taking an ARB was associated with increased hazard ratios [HRs] for low hemoglobin, iron deficiency, diarrhea, and abdominal pain. There weren’t increased risks for weight loss, malabsorption, or vitamin deficiencies.
When excluding those who had an ARB prescription before diagnosis, the HRs remained significantly higher for low hemoglobin (HR, 1.98) and iron deficiency (HR, 1.72) for those who started an ARB after diagnosis.
“The use of angiotensin receptor blockers may be associated with worse outcomes in the setting of celiac disease, specifically persistent symptoms and possibly poor small bowel healing as evidenced by malabsorption,” Hujoel said.
Future studies could look specifically at losartan, which was the most common ARB prescribed in this analysis, she said. Other studies could also analyze different patient outcomes, whether patients were on a gluten-free diet, medication adherence, and recurrence or persistence of symptoms rather than initial occurrence. The associations between ARB use and celiac disease could shift among patients who are in remission, for instance.
“ARBs are some of the most widely used medications, so studies like these can help people to understand that they may have symptoms but not know it’s related to their medication. Public awareness of this fact is key,” said Patricia Jones, MD, a hepatologist and associate professor of clinical medicine at the University of Miami Miller School of Medicine, Miami. Jones co-moderated the plenary session on small intestine, functional, and liver research.
“There are many types of antihypertensives, so while ARBs are used often, other options are available if people have symptoms, especially if they have worsening symptoms with celiac disease,” she said. “It’s important to make changes in your practice.”
The study was named an ACG Newsworthy Abstract. Isabel Hujoel and Patricia Jones reported no relevant disclosures.
A version of this article appeared on Medscape.com.
PHILADELPHIA — , according to a study presented at the American College of Gastroenterology (ACG) 2024 Annual Scientific Meeting.
The association may be related to the similar pathophysiology between ARB-associated enteropathy and celiac disease, though additional research is needed.
“Based on our findings, people should take caution when prescribing angiotensin receptor blockers to people with celiac disease,” said lead author Isabel Hujoel, MD, clinical assistant professor of gastroenterology and clinic director of the Celiac Disease Center at the University of Washington, Seattle.
“When we see someone with nonresponsive celiac disease, meaning persistent symptoms despite a gluten-free diet, I do think we should review their medication list, and if they’re on an ARB, we should consider a trial off those medications to see if they respond,” she said. “A primary care provider may choose other hypertensives as well.”
Hujoel and co-author Margaux Hujoel, PhD, a postdoctoral research fellow at Brigham and Women’s Hospital, Boston; Broad Institute, Cambridge; and Harvard Medical School, Boston, analyzed data from the National Institutes of Health’s All of Us, a large publicly available US longitudinal dataset.
The researchers conducted a survival analysis of time-to-first event after celiac disease diagnosis, allowing patients to have a time-dependent covariate of ARB use. They looked at outcomes such as iron deficiency, diarrhea, abdominal pain, vitamin deficiency, vitamin D deficiency, malabsorption, low hemoglobin, and weight loss.
The analysis included 1849 patients with celiac disease, including 1460 women and 389 men, with a median age of nearly 50 years at diagnosis. While the vast majority of patients (nearly 1600) didn’t take an ARB, 120 started one before celiac disease diagnosis and 142 started one after diagnosis.
Overall, taking an ARB was associated with increased hazard ratios [HRs] for low hemoglobin, iron deficiency, diarrhea, and abdominal pain. There weren’t increased risks for weight loss, malabsorption, or vitamin deficiencies.
When excluding those who had an ARB prescription before diagnosis, the HRs remained significantly higher for low hemoglobin (HR, 1.98) and iron deficiency (HR, 1.72) for those who started an ARB after diagnosis.
“The use of angiotensin receptor blockers may be associated with worse outcomes in the setting of celiac disease, specifically persistent symptoms and possibly poor small bowel healing as evidenced by malabsorption,” Hujoel said.
Future studies could look specifically at losartan, which was the most common ARB prescribed in this analysis, she said. Other studies could also analyze different patient outcomes, whether patients were on a gluten-free diet, medication adherence, and recurrence or persistence of symptoms rather than initial occurrence. The associations between ARB use and celiac disease could shift among patients who are in remission, for instance.
“ARBs are some of the most widely used medications, so studies like these can help people to understand that they may have symptoms but not know it’s related to their medication. Public awareness of this fact is key,” said Patricia Jones, MD, a hepatologist and associate professor of clinical medicine at the University of Miami Miller School of Medicine, Miami. Jones co-moderated the plenary session on small intestine, functional, and liver research.
“There are many types of antihypertensives, so while ARBs are used often, other options are available if people have symptoms, especially if they have worsening symptoms with celiac disease,” she said. “It’s important to make changes in your practice.”
The study was named an ACG Newsworthy Abstract. Isabel Hujoel and Patricia Jones reported no relevant disclosures.
A version of this article appeared on Medscape.com.
PHILADELPHIA — , according to a study presented at the American College of Gastroenterology (ACG) 2024 Annual Scientific Meeting.
The association may be related to the similar pathophysiology between ARB-associated enteropathy and celiac disease, though additional research is needed.
“Based on our findings, people should take caution when prescribing angiotensin receptor blockers to people with celiac disease,” said lead author Isabel Hujoel, MD, clinical assistant professor of gastroenterology and clinic director of the Celiac Disease Center at the University of Washington, Seattle.
“When we see someone with nonresponsive celiac disease, meaning persistent symptoms despite a gluten-free diet, I do think we should review their medication list, and if they’re on an ARB, we should consider a trial off those medications to see if they respond,” she said. “A primary care provider may choose other hypertensives as well.”
Hujoel and co-author Margaux Hujoel, PhD, a postdoctoral research fellow at Brigham and Women’s Hospital, Boston; Broad Institute, Cambridge; and Harvard Medical School, Boston, analyzed data from the National Institutes of Health’s All of Us, a large publicly available US longitudinal dataset.
The researchers conducted a survival analysis of time-to-first event after celiac disease diagnosis, allowing patients to have a time-dependent covariate of ARB use. They looked at outcomes such as iron deficiency, diarrhea, abdominal pain, vitamin deficiency, vitamin D deficiency, malabsorption, low hemoglobin, and weight loss.
The analysis included 1849 patients with celiac disease, including 1460 women and 389 men, with a median age of nearly 50 years at diagnosis. While the vast majority of patients (nearly 1600) didn’t take an ARB, 120 started one before celiac disease diagnosis and 142 started one after diagnosis.
Overall, taking an ARB was associated with increased hazard ratios [HRs] for low hemoglobin, iron deficiency, diarrhea, and abdominal pain. There weren’t increased risks for weight loss, malabsorption, or vitamin deficiencies.
When excluding those who had an ARB prescription before diagnosis, the HRs remained significantly higher for low hemoglobin (HR, 1.98) and iron deficiency (HR, 1.72) for those who started an ARB after diagnosis.
“The use of angiotensin receptor blockers may be associated with worse outcomes in the setting of celiac disease, specifically persistent symptoms and possibly poor small bowel healing as evidenced by malabsorption,” Hujoel said.
Future studies could look specifically at losartan, which was the most common ARB prescribed in this analysis, she said. Other studies could also analyze different patient outcomes, whether patients were on a gluten-free diet, medication adherence, and recurrence or persistence of symptoms rather than initial occurrence. The associations between ARB use and celiac disease could shift among patients who are in remission, for instance.
“ARBs are some of the most widely used medications, so studies like these can help people to understand that they may have symptoms but not know it’s related to their medication. Public awareness of this fact is key,” said Patricia Jones, MD, a hepatologist and associate professor of clinical medicine at the University of Miami Miller School of Medicine, Miami. Jones co-moderated the plenary session on small intestine, functional, and liver research.
“There are many types of antihypertensives, so while ARBs are used often, other options are available if people have symptoms, especially if they have worsening symptoms with celiac disease,” she said. “It’s important to make changes in your practice.”
The study was named an ACG Newsworthy Abstract. Isabel Hujoel and Patricia Jones reported no relevant disclosures.
A version of this article appeared on Medscape.com.
FROM ACG 2024
Shorter H pylori Treatment With Vonoprazan Shows Better Results
PHILADELPHIA — with omeprazole, amoxicillin, and clarithromycin, according to the results of a randomized, multicenter study.
In addition, the triple therapy regimen with vonoprazan was generally better tolerated than the 14-day omeprazole-based regimen.
The new treatment combination was created to tackle the two main reasons that patients with H pylori experience treatment failure: Inadequate acid suppressant activity and antibiotic resistance, said principal investigator Kachonsak Yongwatana, MD, from Phramongkutklao Hospital in Bangkok, Thailand.
“Vonoprazan” is the more potent option for acid suppression, and “levofloxacin” addresses antibiotic resistance, he explained.
Yongwatana presented the findings (Abstract 41) at the American College of Gastroenterology (ACG) 2024 Annual Scientific Meeting. The ACG recently released a clinical guideline on the treatment of H pylori infection.
Robust Eradication Rates
Yongwatana and colleagues enrolled adult patients with H pylori infections at four hospitals in Thailand between December 2022 and September 2023. The presence of H pylori was confirmed by upper gastrointestinal endoscopy with positive rapid urease test or positive test on tissue biopsy.
Patients were then randomized into two treatment groups: The 10-day VAL group (vonoprazan 20 mg twice daily, amoxicillin 1000 mg twice daily, and levofloxacin 500 mg once daily for 10 days) and the 14-day OAC group (omeprazole 20 mg twice daily, amoxicillin 1000 mg twice daily, and clarithromycin 500 mg twice daily for 14 days). Eradication was assessed by urea breath test 4 weeks after completion of treatment.
There were 280 patients in total, with 140 in each group. There were no significant differences in baseline characteristics between the groups. The most common endoscopic findings among all participants included erosive gastritis (38%), nonerosive gastritis (27%), and gastric ulcer (17%).
In comparing the treatments, the researchers found that 10-day VAL led to significantly greater H pylori eradication rate than the 14-day OAC group in both intention-to-treat analysis (91.4 % vs 80.7%, P = .009) and per-protocol analysis (93.4% vs 83.7%, P = .012).
Vonoprazan-based therapy was also well tolerated by participants. Patients in the 10-day VAL group had significantly lower rates of experiencing a bitter taste (2.1% vs 42.9%, P < .001) and bloating (5% vs 12.1%, P = .033) than those in the 14-day OAC group.
Isolating the BMI Effect
The researchers conducted a subgroup analysis on potential factors influencing response, which revealed that having a body mass index (BMI) < 23.5 was significantly associated with a higher chance at successful H pylori eradication (relative risk [RR], 2.27; P = .049).
They then analyzed whether this BMI threshold was predictive in the separate treatment regimens. Although having a BMI < 23.5 was significantly associated with a higher eradication rate in the 14-day OAC group (RR, 3.34; P = .026), no such effect was noted in the 10-day VAL group (RR, 1.10; P = .888).
The influence of BMI could be caused by the bioavailability of the treatments used in the regimen, Younwatana said in an interview. He and his colleagues recommended against using the 14-day OAC regimen in those with BMI ≥ 23.5.
“In patients with a high BMI, we should be concerned that normal proton pump inhibitors may not work,” he said. “You have to step up to the higher-potency options.”
Seeking Confirmation in Other Populations
Session comoderator Felice Schnoll-Sussman, MD, MSc, professor of clinical medicine and the director of the Jay Monahan Center for Gastrointestinal Health, director of the DIGEST program, and the associate chair of medicine for Outreach and Network at New York–Presbyterian Brooklyn Methodist Hospital in New York City, said in an interview that the promising results merit confirmation in other populations.
“When you see a study that is coming out of one country, when there could be issues related to antibiotic sensitivity in H pylori, it really is important to decide whether or not this is applicable to other patient populations,” said Schnoll-Sussman, who was not involved in the study.
She noted that this is also true of the findings from the subgroup as it is unclear whether average rates of BMI are notably lower in Thailand from other countries.
“As we know, BMI affects so many things with disease states. So, it’s a possibility in a country where the BMI is actually lower, there may be something else about these individuals in terms of their wellness status that could be underlying the effect.”
The study had no specific funding, although Takeda supplied treatments used in the analysis. Yongwatana reported no relevant financial relationships. Schnoll-Sussman reported serving as an advisory committee/board member for Braintree, Ethicon, Implantica, and Phathom.
A version of this article first appeared on Medscape.com.
PHILADELPHIA — with omeprazole, amoxicillin, and clarithromycin, according to the results of a randomized, multicenter study.
In addition, the triple therapy regimen with vonoprazan was generally better tolerated than the 14-day omeprazole-based regimen.
The new treatment combination was created to tackle the two main reasons that patients with H pylori experience treatment failure: Inadequate acid suppressant activity and antibiotic resistance, said principal investigator Kachonsak Yongwatana, MD, from Phramongkutklao Hospital in Bangkok, Thailand.
“Vonoprazan” is the more potent option for acid suppression, and “levofloxacin” addresses antibiotic resistance, he explained.
Yongwatana presented the findings (Abstract 41) at the American College of Gastroenterology (ACG) 2024 Annual Scientific Meeting. The ACG recently released a clinical guideline on the treatment of H pylori infection.
Robust Eradication Rates
Yongwatana and colleagues enrolled adult patients with H pylori infections at four hospitals in Thailand between December 2022 and September 2023. The presence of H pylori was confirmed by upper gastrointestinal endoscopy with positive rapid urease test or positive test on tissue biopsy.
Patients were then randomized into two treatment groups: The 10-day VAL group (vonoprazan 20 mg twice daily, amoxicillin 1000 mg twice daily, and levofloxacin 500 mg once daily for 10 days) and the 14-day OAC group (omeprazole 20 mg twice daily, amoxicillin 1000 mg twice daily, and clarithromycin 500 mg twice daily for 14 days). Eradication was assessed by urea breath test 4 weeks after completion of treatment.
There were 280 patients in total, with 140 in each group. There were no significant differences in baseline characteristics between the groups. The most common endoscopic findings among all participants included erosive gastritis (38%), nonerosive gastritis (27%), and gastric ulcer (17%).
In comparing the treatments, the researchers found that 10-day VAL led to significantly greater H pylori eradication rate than the 14-day OAC group in both intention-to-treat analysis (91.4 % vs 80.7%, P = .009) and per-protocol analysis (93.4% vs 83.7%, P = .012).
Vonoprazan-based therapy was also well tolerated by participants. Patients in the 10-day VAL group had significantly lower rates of experiencing a bitter taste (2.1% vs 42.9%, P < .001) and bloating (5% vs 12.1%, P = .033) than those in the 14-day OAC group.
Isolating the BMI Effect
The researchers conducted a subgroup analysis on potential factors influencing response, which revealed that having a body mass index (BMI) < 23.5 was significantly associated with a higher chance at successful H pylori eradication (relative risk [RR], 2.27; P = .049).
They then analyzed whether this BMI threshold was predictive in the separate treatment regimens. Although having a BMI < 23.5 was significantly associated with a higher eradication rate in the 14-day OAC group (RR, 3.34; P = .026), no such effect was noted in the 10-day VAL group (RR, 1.10; P = .888).
The influence of BMI could be caused by the bioavailability of the treatments used in the regimen, Younwatana said in an interview. He and his colleagues recommended against using the 14-day OAC regimen in those with BMI ≥ 23.5.
“In patients with a high BMI, we should be concerned that normal proton pump inhibitors may not work,” he said. “You have to step up to the higher-potency options.”
Seeking Confirmation in Other Populations
Session comoderator Felice Schnoll-Sussman, MD, MSc, professor of clinical medicine and the director of the Jay Monahan Center for Gastrointestinal Health, director of the DIGEST program, and the associate chair of medicine for Outreach and Network at New York–Presbyterian Brooklyn Methodist Hospital in New York City, said in an interview that the promising results merit confirmation in other populations.
“When you see a study that is coming out of one country, when there could be issues related to antibiotic sensitivity in H pylori, it really is important to decide whether or not this is applicable to other patient populations,” said Schnoll-Sussman, who was not involved in the study.
She noted that this is also true of the findings from the subgroup as it is unclear whether average rates of BMI are notably lower in Thailand from other countries.
“As we know, BMI affects so many things with disease states. So, it’s a possibility in a country where the BMI is actually lower, there may be something else about these individuals in terms of their wellness status that could be underlying the effect.”
The study had no specific funding, although Takeda supplied treatments used in the analysis. Yongwatana reported no relevant financial relationships. Schnoll-Sussman reported serving as an advisory committee/board member for Braintree, Ethicon, Implantica, and Phathom.
A version of this article first appeared on Medscape.com.
PHILADELPHIA — with omeprazole, amoxicillin, and clarithromycin, according to the results of a randomized, multicenter study.
In addition, the triple therapy regimen with vonoprazan was generally better tolerated than the 14-day omeprazole-based regimen.
The new treatment combination was created to tackle the two main reasons that patients with H pylori experience treatment failure: Inadequate acid suppressant activity and antibiotic resistance, said principal investigator Kachonsak Yongwatana, MD, from Phramongkutklao Hospital in Bangkok, Thailand.
“Vonoprazan” is the more potent option for acid suppression, and “levofloxacin” addresses antibiotic resistance, he explained.
Yongwatana presented the findings (Abstract 41) at the American College of Gastroenterology (ACG) 2024 Annual Scientific Meeting. The ACG recently released a clinical guideline on the treatment of H pylori infection.
Robust Eradication Rates
Yongwatana and colleagues enrolled adult patients with H pylori infections at four hospitals in Thailand between December 2022 and September 2023. The presence of H pylori was confirmed by upper gastrointestinal endoscopy with positive rapid urease test or positive test on tissue biopsy.
Patients were then randomized into two treatment groups: The 10-day VAL group (vonoprazan 20 mg twice daily, amoxicillin 1000 mg twice daily, and levofloxacin 500 mg once daily for 10 days) and the 14-day OAC group (omeprazole 20 mg twice daily, amoxicillin 1000 mg twice daily, and clarithromycin 500 mg twice daily for 14 days). Eradication was assessed by urea breath test 4 weeks after completion of treatment.
There were 280 patients in total, with 140 in each group. There were no significant differences in baseline characteristics between the groups. The most common endoscopic findings among all participants included erosive gastritis (38%), nonerosive gastritis (27%), and gastric ulcer (17%).
In comparing the treatments, the researchers found that 10-day VAL led to significantly greater H pylori eradication rate than the 14-day OAC group in both intention-to-treat analysis (91.4 % vs 80.7%, P = .009) and per-protocol analysis (93.4% vs 83.7%, P = .012).
Vonoprazan-based therapy was also well tolerated by participants. Patients in the 10-day VAL group had significantly lower rates of experiencing a bitter taste (2.1% vs 42.9%, P < .001) and bloating (5% vs 12.1%, P = .033) than those in the 14-day OAC group.
Isolating the BMI Effect
The researchers conducted a subgroup analysis on potential factors influencing response, which revealed that having a body mass index (BMI) < 23.5 was significantly associated with a higher chance at successful H pylori eradication (relative risk [RR], 2.27; P = .049).
They then analyzed whether this BMI threshold was predictive in the separate treatment regimens. Although having a BMI < 23.5 was significantly associated with a higher eradication rate in the 14-day OAC group (RR, 3.34; P = .026), no such effect was noted in the 10-day VAL group (RR, 1.10; P = .888).
The influence of BMI could be caused by the bioavailability of the treatments used in the regimen, Younwatana said in an interview. He and his colleagues recommended against using the 14-day OAC regimen in those with BMI ≥ 23.5.
“In patients with a high BMI, we should be concerned that normal proton pump inhibitors may not work,” he said. “You have to step up to the higher-potency options.”
Seeking Confirmation in Other Populations
Session comoderator Felice Schnoll-Sussman, MD, MSc, professor of clinical medicine and the director of the Jay Monahan Center for Gastrointestinal Health, director of the DIGEST program, and the associate chair of medicine for Outreach and Network at New York–Presbyterian Brooklyn Methodist Hospital in New York City, said in an interview that the promising results merit confirmation in other populations.
“When you see a study that is coming out of one country, when there could be issues related to antibiotic sensitivity in H pylori, it really is important to decide whether or not this is applicable to other patient populations,” said Schnoll-Sussman, who was not involved in the study.
She noted that this is also true of the findings from the subgroup as it is unclear whether average rates of BMI are notably lower in Thailand from other countries.
“As we know, BMI affects so many things with disease states. So, it’s a possibility in a country where the BMI is actually lower, there may be something else about these individuals in terms of their wellness status that could be underlying the effect.”
The study had no specific funding, although Takeda supplied treatments used in the analysis. Yongwatana reported no relevant financial relationships. Schnoll-Sussman reported serving as an advisory committee/board member for Braintree, Ethicon, Implantica, and Phathom.
A version of this article first appeared on Medscape.com.
FROM ACG 2024
Knowledge Gaps About Obesity Medicine Seen in Primary Care
SAN ANTONIO — Despite the prevalence of obesity in primary care, there appear to be major knowledge gaps among providers regarding obesity management, new research suggests.
Anonymous surveys of 96 primary care providers at a Boston, Massachusetts, safety-net hospital revealed that participants had limited understanding of criteria for prescribing antiobesity medications (AOM), and expressed discomfort in prescribing AOMs because of knowledge concerns, especially for non–glucagon-like peptide 1 (GLP-1) receptor agonists. One third reported that they didn’t prescribe AOMs, and rates of referral for bariatric surgery were also low.
The findings were presented at the Obesity Society’s annual Obesity Week meeting by Alejandro Campos, MD, a third-year resident in the section of internal medicine, Boston Medical Center, and the Department of Medicine, Boston University.
“I think it comes down to education. ... Not only training primary care physicians or residents about criteria and pathophysiology, but also stigma. Perceptions need to be addressed from the start of training in the healthcare field,” Campos told this news organization in an interview.
During his presentation, Campos noted this is the first such study in the setting of a safety-net hospital, which cares for lower-income people who experience disproportionate rates of obesity. But, “these findings are similar to ones observed from non–safety-net settings, which can indicate some potential transferability.”
Asked to comment, session moderator John D. Clark, MD, PhD, Chief Population Health Officer at Sharp Rees-Stealy Medical Group, San Diego, California, told this news organization that the findings didn’t surprise him. “I’d say that medical education around obesity has definitely improved, and training is improving but it’s not uniform. The treatment of obesity as a disease, especially with some of the newer medical treatments, is not standard of care and practiced widely.”
The study involved a standard-model Knowledge, Attitudes, and Practices questionnaire, distributed electronically for anonymous responses among both trained and in-training primary care providers. It contained a total of 43 items, 7 of them demographic, 11 on knowledge, 9 regarding attitudes, and 16 asking about practices.
The hospital is the largest safety-net hospital in New England, with a patient population that includes 58% enrolled in Medicaid, 32% Black/African American individuals, 24% identifying as Hispanic/Latino individuals, and 37% living below the poverty line.
The 96 responding providers (from a total 350 invited) all worked in either family medicine or internal medicine. The trained providers included both attending MDs and nurse practitioners, while those in-training were residents in one of those two specialties. Two thirds were women. The majority were aged 20-30 years (49.45%) or 31-40 years (27.47%).
Overall, 73.63% reported having received some type of obesity training. Just over half (52.08%) reported receiving that training during medical or nursing school, while 43.75% reported receiving it during residency.
When asked to choose from a list of conditions to pick which are considered weight-related comorbidities, between 80% and 90% choose type 2 diabetes, obstructive sleep apnea (OSA), hypertension, hyperlipidemia, nonalcoholic fatty liver disease, and coronary artery disease. Fewer, but still a majority, also listed osteoarthritis and gastroesophageal reflux disease. However, respondents were less likely to cite cancer, mood disorders, or chronic kidney disease as being related to obesity.
Asked to list benefits of a 10% body weight loss, most recognized reductions in OSA, glycemia, cardiovascular disease risk, osteoarthritis, and hepatic steatosis. But, only about half knew weight loss could also improve urinary incontinence.
Only 25% could correctly name both indications for AOMs. Just 27.1% knew that one was a body mass index (BMI) ≥ 27 with comorbidities, while 46.9% knew BMI ≥ 30 without comorbidities was an AOM indication. Only 9.4% were correct on both of those indications for bariatric surgery.
“Reassuringly,” Campos said, the majority either “disagreed” or “strongly disagreed” that “lack of will power” contributes to obesity. However, more than 20% agreed that “lack of exercise or physical activity” contributed.
Overall, 73% of the trained providers and 59% of those in training reported that they prescribe AOMs. Asked about their comfort level in prescribing specific types of AOMs, many more endorsed semaglutide and liraglutide than older medications such as bupropion/naltrexone and phentermine/topiramate.
Asked about factors that influence their comfort with prescribing AOMs, the top five factors selected, in order, were side-effect knowledge, insurance coverage, safety issues, and dosing knowledge. Fewer respondents endorsed “patient’s ideas, concerns, and expectations,” cost, or efficacy.
Referrals to nutrition services were endorsed more often than to obesity medicine specialists or bariatric surgery.
Asked about barriers to obesity treatment in their practices, “time constraints” was the most frequently endorsed, followed by “lack of training or knowledge,” “patient adherence and motivation,” and “limited resources.”
“What are the future directives? We feel we have the need to provide ongoing obesity management, education and assistance to primary care providers, including support for securing coverage for treatments,” Campos said.
He added that Boston Medical Center is now developing and implementing an embedded weight management program within primary care “to assist the front line of obesity care.”
Asked by this news organization whether he believes the rise of GLP-1 drugs will make a difference, Campos said “Definitely, I think with that momentum obesity medicine as a whole will gain more attention and hopefully more implementation in the curricula for medical and nursing schools, because in the end it requires a multidisciplinary approach.”
Campos and Clark had no disclosures.
A version of this article first appeared on Medscape.com.
SAN ANTONIO — Despite the prevalence of obesity in primary care, there appear to be major knowledge gaps among providers regarding obesity management, new research suggests.
Anonymous surveys of 96 primary care providers at a Boston, Massachusetts, safety-net hospital revealed that participants had limited understanding of criteria for prescribing antiobesity medications (AOM), and expressed discomfort in prescribing AOMs because of knowledge concerns, especially for non–glucagon-like peptide 1 (GLP-1) receptor agonists. One third reported that they didn’t prescribe AOMs, and rates of referral for bariatric surgery were also low.
The findings were presented at the Obesity Society’s annual Obesity Week meeting by Alejandro Campos, MD, a third-year resident in the section of internal medicine, Boston Medical Center, and the Department of Medicine, Boston University.
“I think it comes down to education. ... Not only training primary care physicians or residents about criteria and pathophysiology, but also stigma. Perceptions need to be addressed from the start of training in the healthcare field,” Campos told this news organization in an interview.
During his presentation, Campos noted this is the first such study in the setting of a safety-net hospital, which cares for lower-income people who experience disproportionate rates of obesity. But, “these findings are similar to ones observed from non–safety-net settings, which can indicate some potential transferability.”
Asked to comment, session moderator John D. Clark, MD, PhD, Chief Population Health Officer at Sharp Rees-Stealy Medical Group, San Diego, California, told this news organization that the findings didn’t surprise him. “I’d say that medical education around obesity has definitely improved, and training is improving but it’s not uniform. The treatment of obesity as a disease, especially with some of the newer medical treatments, is not standard of care and practiced widely.”
The study involved a standard-model Knowledge, Attitudes, and Practices questionnaire, distributed electronically for anonymous responses among both trained and in-training primary care providers. It contained a total of 43 items, 7 of them demographic, 11 on knowledge, 9 regarding attitudes, and 16 asking about practices.
The hospital is the largest safety-net hospital in New England, with a patient population that includes 58% enrolled in Medicaid, 32% Black/African American individuals, 24% identifying as Hispanic/Latino individuals, and 37% living below the poverty line.
The 96 responding providers (from a total 350 invited) all worked in either family medicine or internal medicine. The trained providers included both attending MDs and nurse practitioners, while those in-training were residents in one of those two specialties. Two thirds were women. The majority were aged 20-30 years (49.45%) or 31-40 years (27.47%).
Overall, 73.63% reported having received some type of obesity training. Just over half (52.08%) reported receiving that training during medical or nursing school, while 43.75% reported receiving it during residency.
When asked to choose from a list of conditions to pick which are considered weight-related comorbidities, between 80% and 90% choose type 2 diabetes, obstructive sleep apnea (OSA), hypertension, hyperlipidemia, nonalcoholic fatty liver disease, and coronary artery disease. Fewer, but still a majority, also listed osteoarthritis and gastroesophageal reflux disease. However, respondents were less likely to cite cancer, mood disorders, or chronic kidney disease as being related to obesity.
Asked to list benefits of a 10% body weight loss, most recognized reductions in OSA, glycemia, cardiovascular disease risk, osteoarthritis, and hepatic steatosis. But, only about half knew weight loss could also improve urinary incontinence.
Only 25% could correctly name both indications for AOMs. Just 27.1% knew that one was a body mass index (BMI) ≥ 27 with comorbidities, while 46.9% knew BMI ≥ 30 without comorbidities was an AOM indication. Only 9.4% were correct on both of those indications for bariatric surgery.
“Reassuringly,” Campos said, the majority either “disagreed” or “strongly disagreed” that “lack of will power” contributes to obesity. However, more than 20% agreed that “lack of exercise or physical activity” contributed.
Overall, 73% of the trained providers and 59% of those in training reported that they prescribe AOMs. Asked about their comfort level in prescribing specific types of AOMs, many more endorsed semaglutide and liraglutide than older medications such as bupropion/naltrexone and phentermine/topiramate.
Asked about factors that influence their comfort with prescribing AOMs, the top five factors selected, in order, were side-effect knowledge, insurance coverage, safety issues, and dosing knowledge. Fewer respondents endorsed “patient’s ideas, concerns, and expectations,” cost, or efficacy.
Referrals to nutrition services were endorsed more often than to obesity medicine specialists or bariatric surgery.
Asked about barriers to obesity treatment in their practices, “time constraints” was the most frequently endorsed, followed by “lack of training or knowledge,” “patient adherence and motivation,” and “limited resources.”
“What are the future directives? We feel we have the need to provide ongoing obesity management, education and assistance to primary care providers, including support for securing coverage for treatments,” Campos said.
He added that Boston Medical Center is now developing and implementing an embedded weight management program within primary care “to assist the front line of obesity care.”
Asked by this news organization whether he believes the rise of GLP-1 drugs will make a difference, Campos said “Definitely, I think with that momentum obesity medicine as a whole will gain more attention and hopefully more implementation in the curricula for medical and nursing schools, because in the end it requires a multidisciplinary approach.”
Campos and Clark had no disclosures.
A version of this article first appeared on Medscape.com.
SAN ANTONIO — Despite the prevalence of obesity in primary care, there appear to be major knowledge gaps among providers regarding obesity management, new research suggests.
Anonymous surveys of 96 primary care providers at a Boston, Massachusetts, safety-net hospital revealed that participants had limited understanding of criteria for prescribing antiobesity medications (AOM), and expressed discomfort in prescribing AOMs because of knowledge concerns, especially for non–glucagon-like peptide 1 (GLP-1) receptor agonists. One third reported that they didn’t prescribe AOMs, and rates of referral for bariatric surgery were also low.
The findings were presented at the Obesity Society’s annual Obesity Week meeting by Alejandro Campos, MD, a third-year resident in the section of internal medicine, Boston Medical Center, and the Department of Medicine, Boston University.
“I think it comes down to education. ... Not only training primary care physicians or residents about criteria and pathophysiology, but also stigma. Perceptions need to be addressed from the start of training in the healthcare field,” Campos told this news organization in an interview.
During his presentation, Campos noted this is the first such study in the setting of a safety-net hospital, which cares for lower-income people who experience disproportionate rates of obesity. But, “these findings are similar to ones observed from non–safety-net settings, which can indicate some potential transferability.”
Asked to comment, session moderator John D. Clark, MD, PhD, Chief Population Health Officer at Sharp Rees-Stealy Medical Group, San Diego, California, told this news organization that the findings didn’t surprise him. “I’d say that medical education around obesity has definitely improved, and training is improving but it’s not uniform. The treatment of obesity as a disease, especially with some of the newer medical treatments, is not standard of care and practiced widely.”
The study involved a standard-model Knowledge, Attitudes, and Practices questionnaire, distributed electronically for anonymous responses among both trained and in-training primary care providers. It contained a total of 43 items, 7 of them demographic, 11 on knowledge, 9 regarding attitudes, and 16 asking about practices.
The hospital is the largest safety-net hospital in New England, with a patient population that includes 58% enrolled in Medicaid, 32% Black/African American individuals, 24% identifying as Hispanic/Latino individuals, and 37% living below the poverty line.
The 96 responding providers (from a total 350 invited) all worked in either family medicine or internal medicine. The trained providers included both attending MDs and nurse practitioners, while those in-training were residents in one of those two specialties. Two thirds were women. The majority were aged 20-30 years (49.45%) or 31-40 years (27.47%).
Overall, 73.63% reported having received some type of obesity training. Just over half (52.08%) reported receiving that training during medical or nursing school, while 43.75% reported receiving it during residency.
When asked to choose from a list of conditions to pick which are considered weight-related comorbidities, between 80% and 90% choose type 2 diabetes, obstructive sleep apnea (OSA), hypertension, hyperlipidemia, nonalcoholic fatty liver disease, and coronary artery disease. Fewer, but still a majority, also listed osteoarthritis and gastroesophageal reflux disease. However, respondents were less likely to cite cancer, mood disorders, or chronic kidney disease as being related to obesity.
Asked to list benefits of a 10% body weight loss, most recognized reductions in OSA, glycemia, cardiovascular disease risk, osteoarthritis, and hepatic steatosis. But, only about half knew weight loss could also improve urinary incontinence.
Only 25% could correctly name both indications for AOMs. Just 27.1% knew that one was a body mass index (BMI) ≥ 27 with comorbidities, while 46.9% knew BMI ≥ 30 without comorbidities was an AOM indication. Only 9.4% were correct on both of those indications for bariatric surgery.
“Reassuringly,” Campos said, the majority either “disagreed” or “strongly disagreed” that “lack of will power” contributes to obesity. However, more than 20% agreed that “lack of exercise or physical activity” contributed.
Overall, 73% of the trained providers and 59% of those in training reported that they prescribe AOMs. Asked about their comfort level in prescribing specific types of AOMs, many more endorsed semaglutide and liraglutide than older medications such as bupropion/naltrexone and phentermine/topiramate.
Asked about factors that influence their comfort with prescribing AOMs, the top five factors selected, in order, were side-effect knowledge, insurance coverage, safety issues, and dosing knowledge. Fewer respondents endorsed “patient’s ideas, concerns, and expectations,” cost, or efficacy.
Referrals to nutrition services were endorsed more often than to obesity medicine specialists or bariatric surgery.
Asked about barriers to obesity treatment in their practices, “time constraints” was the most frequently endorsed, followed by “lack of training or knowledge,” “patient adherence and motivation,” and “limited resources.”
“What are the future directives? We feel we have the need to provide ongoing obesity management, education and assistance to primary care providers, including support for securing coverage for treatments,” Campos said.
He added that Boston Medical Center is now developing and implementing an embedded weight management program within primary care “to assist the front line of obesity care.”
Asked by this news organization whether he believes the rise of GLP-1 drugs will make a difference, Campos said “Definitely, I think with that momentum obesity medicine as a whole will gain more attention and hopefully more implementation in the curricula for medical and nursing schools, because in the end it requires a multidisciplinary approach.”
Campos and Clark had no disclosures.
A version of this article first appeared on Medscape.com.
FROM OBESITY WEEK 2024
AI-Assisted Colonoscopy Linked to Higher Rate of Benign Lesion Removal
PHILADELPHIA — according to a study presented at the annual meeting of the American College of Gastroenterology (ACG).
In particular, AIAC led to a statistically and clinically significant increase in the proportion of exams that detected lesions that after resection were all found to be benign, compared with unassisted colonoscopy.
“The potential implications include increased procedural risks, as well as costs, such as pathology costs and other healthcare expenditures, without any additional colorectal cancer prevention benefit,” said lead author Tessa Herman, MD, chief resident of internal medicine at the University of Minnesota, Minneapolis, and Minneapolis Veterans Affairs Health Care System.
In a previous implementation trial at the Minneapolis VA Medical Center, Herman and colleagues compared ADR between a group of patients undergoing AIAC and a historical cohort of patients who had non–AI-assisted colonoscopy.
In this subsequent study, the research team conducted an ad hoc analysis of data from the previous trial to determine the proportion of colonoscopies for screening, surveillance, and positive fecal immunochemical tests which detect lesions that after resection are all found to be benign. They excluded colonoscopies conducted for diagnostic indications or inflammatory bowel disease, as well as incomplete colonoscopies, and for those with inadequate bowel preparation.
Overall, they studied 441 non-AIAC colonoscopies (between November 2022 and April 2023) and 599 AIAC colonoscopies (between May 2023 and October 2023). The groups were balanced, and there were no significant differences in patient demographics, endoscopists, AI technology, procedure time, or average number of polyps detected.
In the non-AIAC cohort, 37 cases (8.4%) had polypectomies that revealed only benign lesions, as compared with 74 cases (12.4%) in the AIAC cohort. The most common resected lesions were benign colonic mucosa, lymphoid aggregates, and hyperplastic polyps.
Applied to the 15 million colonoscopies conducted in the United States per year, the findings indicate that full adoption of AIAC could result in about 600,000 more colonoscopies in which only benign, nonadenomatous lesions are removed, compared with traditional colonoscopy, Herman said.
More study of AIAC is needed, said Daniel Pambianco, MD, managing partner of GastroHealth-Charlottesville in Virginia and the 2023 ACG president. “This technology is in a fledging stage, and the more data we have, the more helpful it’ll be to know if we’re removing the right lesions at a better rate.”
“There’s a hope that assistance will improve detection, removal of polyps, and ultimately, colon cancer,” added Pambianco, who comoderated the session on colorectal cancer prevention.
Future longitudinal studies should monitor both ADR and benign lesion resection rates with AIAC, and modeling studies could determine the benefits and costs of the technology, Herman said. In addition, development of hybrid CADe and computer-aided diagnosis systems could mitigate concerns about excessive benign lesion resection with AI tools.
Clinicians already are able to find colon mucosa that are polypoid or lymphoid aggregates during colonoscopy without AI assistance, said the session’s comoderator, Sita Chokhavatia, MD, AGAF, a gastroenterologist with Valley Medical Group in Ridgewood, New Jersey.
“Instead, we need a tool that can help us to not remove these polyps that are not neoplastic,” she said. “With future developments, we may be able to take it to the next step where the algorithm tells us that it’s benign and not to touch it.”
The study was named an ACG Newsworthy Abstract. Herman, Pambianco, and Chokhavatia reported no relevant disclosures.
A version of this article first appeared on Medscape.com.
PHILADELPHIA — according to a study presented at the annual meeting of the American College of Gastroenterology (ACG).
In particular, AIAC led to a statistically and clinically significant increase in the proportion of exams that detected lesions that after resection were all found to be benign, compared with unassisted colonoscopy.
“The potential implications include increased procedural risks, as well as costs, such as pathology costs and other healthcare expenditures, without any additional colorectal cancer prevention benefit,” said lead author Tessa Herman, MD, chief resident of internal medicine at the University of Minnesota, Minneapolis, and Minneapolis Veterans Affairs Health Care System.
In a previous implementation trial at the Minneapolis VA Medical Center, Herman and colleagues compared ADR between a group of patients undergoing AIAC and a historical cohort of patients who had non–AI-assisted colonoscopy.
In this subsequent study, the research team conducted an ad hoc analysis of data from the previous trial to determine the proportion of colonoscopies for screening, surveillance, and positive fecal immunochemical tests which detect lesions that after resection are all found to be benign. They excluded colonoscopies conducted for diagnostic indications or inflammatory bowel disease, as well as incomplete colonoscopies, and for those with inadequate bowel preparation.
Overall, they studied 441 non-AIAC colonoscopies (between November 2022 and April 2023) and 599 AIAC colonoscopies (between May 2023 and October 2023). The groups were balanced, and there were no significant differences in patient demographics, endoscopists, AI technology, procedure time, or average number of polyps detected.
In the non-AIAC cohort, 37 cases (8.4%) had polypectomies that revealed only benign lesions, as compared with 74 cases (12.4%) in the AIAC cohort. The most common resected lesions were benign colonic mucosa, lymphoid aggregates, and hyperplastic polyps.
Applied to the 15 million colonoscopies conducted in the United States per year, the findings indicate that full adoption of AIAC could result in about 600,000 more colonoscopies in which only benign, nonadenomatous lesions are removed, compared with traditional colonoscopy, Herman said.
More study of AIAC is needed, said Daniel Pambianco, MD, managing partner of GastroHealth-Charlottesville in Virginia and the 2023 ACG president. “This technology is in a fledging stage, and the more data we have, the more helpful it’ll be to know if we’re removing the right lesions at a better rate.”
“There’s a hope that assistance will improve detection, removal of polyps, and ultimately, colon cancer,” added Pambianco, who comoderated the session on colorectal cancer prevention.
Future longitudinal studies should monitor both ADR and benign lesion resection rates with AIAC, and modeling studies could determine the benefits and costs of the technology, Herman said. In addition, development of hybrid CADe and computer-aided diagnosis systems could mitigate concerns about excessive benign lesion resection with AI tools.
Clinicians already are able to find colon mucosa that are polypoid or lymphoid aggregates during colonoscopy without AI assistance, said the session’s comoderator, Sita Chokhavatia, MD, AGAF, a gastroenterologist with Valley Medical Group in Ridgewood, New Jersey.
“Instead, we need a tool that can help us to not remove these polyps that are not neoplastic,” she said. “With future developments, we may be able to take it to the next step where the algorithm tells us that it’s benign and not to touch it.”
The study was named an ACG Newsworthy Abstract. Herman, Pambianco, and Chokhavatia reported no relevant disclosures.
A version of this article first appeared on Medscape.com.
PHILADELPHIA — according to a study presented at the annual meeting of the American College of Gastroenterology (ACG).
In particular, AIAC led to a statistically and clinically significant increase in the proportion of exams that detected lesions that after resection were all found to be benign, compared with unassisted colonoscopy.
“The potential implications include increased procedural risks, as well as costs, such as pathology costs and other healthcare expenditures, without any additional colorectal cancer prevention benefit,” said lead author Tessa Herman, MD, chief resident of internal medicine at the University of Minnesota, Minneapolis, and Minneapolis Veterans Affairs Health Care System.
In a previous implementation trial at the Minneapolis VA Medical Center, Herman and colleagues compared ADR between a group of patients undergoing AIAC and a historical cohort of patients who had non–AI-assisted colonoscopy.
In this subsequent study, the research team conducted an ad hoc analysis of data from the previous trial to determine the proportion of colonoscopies for screening, surveillance, and positive fecal immunochemical tests which detect lesions that after resection are all found to be benign. They excluded colonoscopies conducted for diagnostic indications or inflammatory bowel disease, as well as incomplete colonoscopies, and for those with inadequate bowel preparation.
Overall, they studied 441 non-AIAC colonoscopies (between November 2022 and April 2023) and 599 AIAC colonoscopies (between May 2023 and October 2023). The groups were balanced, and there were no significant differences in patient demographics, endoscopists, AI technology, procedure time, or average number of polyps detected.
In the non-AIAC cohort, 37 cases (8.4%) had polypectomies that revealed only benign lesions, as compared with 74 cases (12.4%) in the AIAC cohort. The most common resected lesions were benign colonic mucosa, lymphoid aggregates, and hyperplastic polyps.
Applied to the 15 million colonoscopies conducted in the United States per year, the findings indicate that full adoption of AIAC could result in about 600,000 more colonoscopies in which only benign, nonadenomatous lesions are removed, compared with traditional colonoscopy, Herman said.
More study of AIAC is needed, said Daniel Pambianco, MD, managing partner of GastroHealth-Charlottesville in Virginia and the 2023 ACG president. “This technology is in a fledging stage, and the more data we have, the more helpful it’ll be to know if we’re removing the right lesions at a better rate.”
“There’s a hope that assistance will improve detection, removal of polyps, and ultimately, colon cancer,” added Pambianco, who comoderated the session on colorectal cancer prevention.
Future longitudinal studies should monitor both ADR and benign lesion resection rates with AIAC, and modeling studies could determine the benefits and costs of the technology, Herman said. In addition, development of hybrid CADe and computer-aided diagnosis systems could mitigate concerns about excessive benign lesion resection with AI tools.
Clinicians already are able to find colon mucosa that are polypoid or lymphoid aggregates during colonoscopy without AI assistance, said the session’s comoderator, Sita Chokhavatia, MD, AGAF, a gastroenterologist with Valley Medical Group in Ridgewood, New Jersey.
“Instead, we need a tool that can help us to not remove these polyps that are not neoplastic,” she said. “With future developments, we may be able to take it to the next step where the algorithm tells us that it’s benign and not to touch it.”
The study was named an ACG Newsworthy Abstract. Herman, Pambianco, and Chokhavatia reported no relevant disclosures.
A version of this article first appeared on Medscape.com.
FROM ACG 2024
Short-Course Vasoconstrictors After EVL: Time for a New Standard of Care?
PHILADELPHIA — without raising the risk for rebleeding, if the initial ligation successfully controls bleeding.
“This approach would allow earlier discharge from the hospital and reduce the risk of adverse events, all without sacrificing treatment efficacy or compromising patient safety,” Sushrut Ingawale, MD, MBBS, Quinnipiac University School of Medicine, North Haven, and St. Vincent’s Medical Center, Bridgeport, both in Connecticut, said in a presentation at the annual meeting of the American College of Gastroenterology (ACG).
Ingawale called for a “re-evaluation of existing protocols, emphasizing the potential to update current protocols to reflect shorter, more personalized” duration of vasoconstrictor therapy in these patients.
Commenting on this research, Nancy Reau, MD, AGAF, of Rush University in Chicago, Illinois, said: “We should always question the standard of care.”
“Vasoconstrictors for 5 days is the standard of care, but this could lead to prolonged hospitalization in patients who are otherwise doing well after endoscopic intervention. Recognizing that a shorter course of vasoconstrictor treatment may have equal outcome is very important though it may not be appropriate for all patients, especially those at high risk for rebleeding,” said Reau.
Outdated Guidelines?
In his presentation, Ingawale noted that current guidelines that recommend continuing vasoconstrictors, like octreotide or terlipressin, for at least 3-5 days after EVL for acute variceal bleeding are based primarily on old studies in which sclerotherapy was the primary hemostatic method.
The study team assessed comparative outcomes based on the duration of vasoconstrictors after EVL for acute variceal bleeding in a systematic review and network meta-analysis of 11 randomized controlled trials.
The studies had a total of 816 patients who were grouped based on the duration vasoconstrictor therapy: 24 hours or less (group 1), 24-72 hours (group 2), and 72-120 hours (group 3).
There was no significant difference in the risk for rebleeding in group 1 (risk ratio [RR], 1.36; 95% CI, 0.48-3.52) and group 2 (RR, 1.34; 95% CI, 0.42-4.54) vs group 3.
“This finding was even consistent when we compared individual durations” of 0, 12, 24, 48, and 72 hours vs 120 hours, Ingawale said.
There was also no statistically significant difference in the 5-day mortality risk between group 1 (RR, 0.66; 95% CI, 0.09-2.52) and group 2 (RR, 1.08; 95% CI, 0.15-6.43) or the 30-day mortality risk between group 1 (RR, 1.18; 95% CI, 0.51-2.51) and group 2 (RR, 0.98; 95% CI, 0.36-2.52) vs group 3.
Rapidly Evolving Area
“Our network meta-analysis did not show any benefit of continuing vasoconstrictors after EVL,” the researchers wrote in their conference abstract. Despite historical precedent, shorter durations may be adequate, “potentially enabling earlier hospital discharge without compromising patient outcomes.”
Ingawale suggested future research should look to identify the subset of patients at a risk for failure to control bleeding who might benefit from the continuation of vasoconstrictors.
“Management of complications of portal hypertension are rapidly evolving and this study will add to the data that drives our guidelines. Seeing this data in a peer reviewed publication will add the necessary validity to impact a change in the treatment paradigm,” Reau said.
The study had no specific funding. Ingawale had no relevant financial relationships. Reau disclosed various relationships with AbbVie, Gilead, Arbutus, Intercept, and Salix.
A version of this article first appeared on Medscape.com.
PHILADELPHIA — without raising the risk for rebleeding, if the initial ligation successfully controls bleeding.
“This approach would allow earlier discharge from the hospital and reduce the risk of adverse events, all without sacrificing treatment efficacy or compromising patient safety,” Sushrut Ingawale, MD, MBBS, Quinnipiac University School of Medicine, North Haven, and St. Vincent’s Medical Center, Bridgeport, both in Connecticut, said in a presentation at the annual meeting of the American College of Gastroenterology (ACG).
Ingawale called for a “re-evaluation of existing protocols, emphasizing the potential to update current protocols to reflect shorter, more personalized” duration of vasoconstrictor therapy in these patients.
Commenting on this research, Nancy Reau, MD, AGAF, of Rush University in Chicago, Illinois, said: “We should always question the standard of care.”
“Vasoconstrictors for 5 days is the standard of care, but this could lead to prolonged hospitalization in patients who are otherwise doing well after endoscopic intervention. Recognizing that a shorter course of vasoconstrictor treatment may have equal outcome is very important though it may not be appropriate for all patients, especially those at high risk for rebleeding,” said Reau.
Outdated Guidelines?
In his presentation, Ingawale noted that current guidelines that recommend continuing vasoconstrictors, like octreotide or terlipressin, for at least 3-5 days after EVL for acute variceal bleeding are based primarily on old studies in which sclerotherapy was the primary hemostatic method.
The study team assessed comparative outcomes based on the duration of vasoconstrictors after EVL for acute variceal bleeding in a systematic review and network meta-analysis of 11 randomized controlled trials.
The studies had a total of 816 patients who were grouped based on the duration vasoconstrictor therapy: 24 hours or less (group 1), 24-72 hours (group 2), and 72-120 hours (group 3).
There was no significant difference in the risk for rebleeding in group 1 (risk ratio [RR], 1.36; 95% CI, 0.48-3.52) and group 2 (RR, 1.34; 95% CI, 0.42-4.54) vs group 3.
“This finding was even consistent when we compared individual durations” of 0, 12, 24, 48, and 72 hours vs 120 hours, Ingawale said.
There was also no statistically significant difference in the 5-day mortality risk between group 1 (RR, 0.66; 95% CI, 0.09-2.52) and group 2 (RR, 1.08; 95% CI, 0.15-6.43) or the 30-day mortality risk between group 1 (RR, 1.18; 95% CI, 0.51-2.51) and group 2 (RR, 0.98; 95% CI, 0.36-2.52) vs group 3.
Rapidly Evolving Area
“Our network meta-analysis did not show any benefit of continuing vasoconstrictors after EVL,” the researchers wrote in their conference abstract. Despite historical precedent, shorter durations may be adequate, “potentially enabling earlier hospital discharge without compromising patient outcomes.”
Ingawale suggested future research should look to identify the subset of patients at a risk for failure to control bleeding who might benefit from the continuation of vasoconstrictors.
“Management of complications of portal hypertension are rapidly evolving and this study will add to the data that drives our guidelines. Seeing this data in a peer reviewed publication will add the necessary validity to impact a change in the treatment paradigm,” Reau said.
The study had no specific funding. Ingawale had no relevant financial relationships. Reau disclosed various relationships with AbbVie, Gilead, Arbutus, Intercept, and Salix.
A version of this article first appeared on Medscape.com.
PHILADELPHIA — without raising the risk for rebleeding, if the initial ligation successfully controls bleeding.
“This approach would allow earlier discharge from the hospital and reduce the risk of adverse events, all without sacrificing treatment efficacy or compromising patient safety,” Sushrut Ingawale, MD, MBBS, Quinnipiac University School of Medicine, North Haven, and St. Vincent’s Medical Center, Bridgeport, both in Connecticut, said in a presentation at the annual meeting of the American College of Gastroenterology (ACG).
Ingawale called for a “re-evaluation of existing protocols, emphasizing the potential to update current protocols to reflect shorter, more personalized” duration of vasoconstrictor therapy in these patients.
Commenting on this research, Nancy Reau, MD, AGAF, of Rush University in Chicago, Illinois, said: “We should always question the standard of care.”
“Vasoconstrictors for 5 days is the standard of care, but this could lead to prolonged hospitalization in patients who are otherwise doing well after endoscopic intervention. Recognizing that a shorter course of vasoconstrictor treatment may have equal outcome is very important though it may not be appropriate for all patients, especially those at high risk for rebleeding,” said Reau.
Outdated Guidelines?
In his presentation, Ingawale noted that current guidelines that recommend continuing vasoconstrictors, like octreotide or terlipressin, for at least 3-5 days after EVL for acute variceal bleeding are based primarily on old studies in which sclerotherapy was the primary hemostatic method.
The study team assessed comparative outcomes based on the duration of vasoconstrictors after EVL for acute variceal bleeding in a systematic review and network meta-analysis of 11 randomized controlled trials.
The studies had a total of 816 patients who were grouped based on the duration vasoconstrictor therapy: 24 hours or less (group 1), 24-72 hours (group 2), and 72-120 hours (group 3).
There was no significant difference in the risk for rebleeding in group 1 (risk ratio [RR], 1.36; 95% CI, 0.48-3.52) and group 2 (RR, 1.34; 95% CI, 0.42-4.54) vs group 3.
“This finding was even consistent when we compared individual durations” of 0, 12, 24, 48, and 72 hours vs 120 hours, Ingawale said.
There was also no statistically significant difference in the 5-day mortality risk between group 1 (RR, 0.66; 95% CI, 0.09-2.52) and group 2 (RR, 1.08; 95% CI, 0.15-6.43) or the 30-day mortality risk between group 1 (RR, 1.18; 95% CI, 0.51-2.51) and group 2 (RR, 0.98; 95% CI, 0.36-2.52) vs group 3.
Rapidly Evolving Area
“Our network meta-analysis did not show any benefit of continuing vasoconstrictors after EVL,” the researchers wrote in their conference abstract. Despite historical precedent, shorter durations may be adequate, “potentially enabling earlier hospital discharge without compromising patient outcomes.”
Ingawale suggested future research should look to identify the subset of patients at a risk for failure to control bleeding who might benefit from the continuation of vasoconstrictors.
“Management of complications of portal hypertension are rapidly evolving and this study will add to the data that drives our guidelines. Seeing this data in a peer reviewed publication will add the necessary validity to impact a change in the treatment paradigm,” Reau said.
The study had no specific funding. Ingawale had no relevant financial relationships. Reau disclosed various relationships with AbbVie, Gilead, Arbutus, Intercept, and Salix.
A version of this article first appeared on Medscape.com.
FROM ACG 2024
Myasthenia Gravis: Where Does Traditional Therapy Fit In?
SAVANNAH, GEORGIA —
In a debate at American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) 2024, a pair of neurologists who specialize in neuromuscular disorders laid out opposing evidence for each approach.
On one hand, Benjamin Claytor, MD, of Cleveland Clinic, Cleveland, argued that “traditional therapy is very effective for the majority of myasthenia gravis patients,” and he said it should be considered first-line.
But Amanda C. Guidon, MD, MPH, of Massachusetts General Hospital and Harvard Medical School, both in Boston, responded that “the immunosuppression of traditional therapies is too broad: The time to benefit is too long, the burden of side effects is too high, and the cancer risk is too elevated.”
Traditional Therapy: Affordable, Tolerable, and Safe?
Claytor said ideal myasthenia gravis therapies are effective, tolerable, and safe. They’re also affordable, convenient (such as a pill), lead to sustained remission, and can have dosages reduced.
Only traditional therapies — corticosteroids, azathioprine, mycophenolate, and rituximab — meet those last three criteria, he said. Newer therapies, he said, do not.
Claytor highlighted a 2023 Duke University study that tracked 367 patients with MG who were treated with traditional therapies after the year 2000. Of those, 72% reached the treatment goal of minimal manifestations in a median of less than 2 years.
In addition, Claytor noted that the percentage of patients with myasthenia gravis who reach minimal symptom expression ranges from 45% (6 months) to 60% or more (2 years), while studies suggest that newer treatments such as eculizumab (Soliris), efgartigimod (Vyvgart), rozanolixizumab (Rystiggo), and zilucoplan (Zilbrysq) haven’t reached those levels.
As for specific traditional therapies, Claytor said the corticosteroid prednisone is “extremely affordable,” effective, and takes fewer than 2 weeks to work. All patients with myasthenia gravis can take it, he said, and at least 75% of those with mild/moderate disease respond to low doses.
Nonsteroidal Agents, Immune Globulin, Rituximab
He acknowledged side effects from corticosteroids but said doses can be tapered once severity improves. Calcium and vitamin D can be helpful to support bone health, he added.
As for nonsteroidal immunosuppressive treatments, he said they’re easy to administer, increase the likelihood of reaching minimal manifestation status, can be effective at lower doses, and may allow patients to discontinue steroids.
Two other traditional therapies, immune globulin and plasmapheresis, can be appropriate in crisis or impending crisis situations, he said, or as an add-on therapy if steroids and nonsteroidal immunosuppressive therapies don’t work.
What about rituximab? “We’re learning that patients with new-onset disease and younger patients seem to respond better,” Claytor said. While rituximab is expensive, it’s “not even in the same realm” as newer agents if only a dose or two are given, he said.
Steroids Are Ideal in MG? Not So Fast
In her response, Guidon noted that she was assigned to offer a counter-perspective in her presentation, and “personal opinions are not being represented here fully.” She then listed the weaknesses of traditional therapy in myasthenia gravis.
For one thing, she said the drugs don’t work well. She highlighted a 2019 registry study that found “many myasthenia gravis patients remain negatively impacted despite treatment.”
In addition, “we can’t predict who will respond to which therapy. ... We start drugs and don’t know if we’ll have benefit from 6 months up to 18 months. We also can’t determine minimally effective dose a priori. Some patients require higher doses, and some subtherapeutic doses are actually therapeutic for our patients.”
Broad immunosuppression, she added, boosts the risk for serious infections. “We’ve all heard from our patients that the side effects can be worse than the myasthenia, and next we’re going to talk about the role of corticosteroids in myasthenia.”
As for corticosteroids in particular, “they’re really the best treatment and also the worst treatment.” Efficacy and side effects battle for supremacy in patients, she said, “and you don’t know which is going to win out.”
Kicking Traditional Therapy to the Curb
There are many possible side effects from steroids, she said, including steroid-induced diabetes, which is “profound.” Some patients never recover from it.
On top of all these risks, she said, 20%-30% of patients are resistant to steroids.
As for other treatments, immune globulin and plasmapheresis “aren’t really benign,” Guidon said. They come with potentially serious side effects of their own, as do nonsteroidal immunosuppressive treatments.
Guidon said better treatments are needed to minimize the risks from traditional therapies. “We need targeted therapies that drive disease into remission, can be tapered, are delivered orally or with infrequent self-injections, and don’t require frequent lab monitoring.”
In addition, ideal treatments should “have a good safety data in pregnancy and for breastfeeding and have a favorable side effect profile with no significant long-term cancer risks.”
Claytor had no disclosures. Guidon disclosed consulting/medical advisory board (Alexion Pharmaceuticals, argenx, Regeneron, and UCB), publishing royalties (Oakstone), and other research support (Myasthenia Gravis Foundation of America, Myasthenia Gravis Rare Disease Network, National Institutes of Health, and National Institute of Neurological Disorders and Stroke/BioSensics).
A version of this article appeared on Medscape.com.
SAVANNAH, GEORGIA —
In a debate at American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) 2024, a pair of neurologists who specialize in neuromuscular disorders laid out opposing evidence for each approach.
On one hand, Benjamin Claytor, MD, of Cleveland Clinic, Cleveland, argued that “traditional therapy is very effective for the majority of myasthenia gravis patients,” and he said it should be considered first-line.
But Amanda C. Guidon, MD, MPH, of Massachusetts General Hospital and Harvard Medical School, both in Boston, responded that “the immunosuppression of traditional therapies is too broad: The time to benefit is too long, the burden of side effects is too high, and the cancer risk is too elevated.”
Traditional Therapy: Affordable, Tolerable, and Safe?
Claytor said ideal myasthenia gravis therapies are effective, tolerable, and safe. They’re also affordable, convenient (such as a pill), lead to sustained remission, and can have dosages reduced.
Only traditional therapies — corticosteroids, azathioprine, mycophenolate, and rituximab — meet those last three criteria, he said. Newer therapies, he said, do not.
Claytor highlighted a 2023 Duke University study that tracked 367 patients with MG who were treated with traditional therapies after the year 2000. Of those, 72% reached the treatment goal of minimal manifestations in a median of less than 2 years.
In addition, Claytor noted that the percentage of patients with myasthenia gravis who reach minimal symptom expression ranges from 45% (6 months) to 60% or more (2 years), while studies suggest that newer treatments such as eculizumab (Soliris), efgartigimod (Vyvgart), rozanolixizumab (Rystiggo), and zilucoplan (Zilbrysq) haven’t reached those levels.
As for specific traditional therapies, Claytor said the corticosteroid prednisone is “extremely affordable,” effective, and takes fewer than 2 weeks to work. All patients with myasthenia gravis can take it, he said, and at least 75% of those with mild/moderate disease respond to low doses.
Nonsteroidal Agents, Immune Globulin, Rituximab
He acknowledged side effects from corticosteroids but said doses can be tapered once severity improves. Calcium and vitamin D can be helpful to support bone health, he added.
As for nonsteroidal immunosuppressive treatments, he said they’re easy to administer, increase the likelihood of reaching minimal manifestation status, can be effective at lower doses, and may allow patients to discontinue steroids.
Two other traditional therapies, immune globulin and plasmapheresis, can be appropriate in crisis or impending crisis situations, he said, or as an add-on therapy if steroids and nonsteroidal immunosuppressive therapies don’t work.
What about rituximab? “We’re learning that patients with new-onset disease and younger patients seem to respond better,” Claytor said. While rituximab is expensive, it’s “not even in the same realm” as newer agents if only a dose or two are given, he said.
Steroids Are Ideal in MG? Not So Fast
In her response, Guidon noted that she was assigned to offer a counter-perspective in her presentation, and “personal opinions are not being represented here fully.” She then listed the weaknesses of traditional therapy in myasthenia gravis.
For one thing, she said the drugs don’t work well. She highlighted a 2019 registry study that found “many myasthenia gravis patients remain negatively impacted despite treatment.”
In addition, “we can’t predict who will respond to which therapy. ... We start drugs and don’t know if we’ll have benefit from 6 months up to 18 months. We also can’t determine minimally effective dose a priori. Some patients require higher doses, and some subtherapeutic doses are actually therapeutic for our patients.”
Broad immunosuppression, she added, boosts the risk for serious infections. “We’ve all heard from our patients that the side effects can be worse than the myasthenia, and next we’re going to talk about the role of corticosteroids in myasthenia.”
As for corticosteroids in particular, “they’re really the best treatment and also the worst treatment.” Efficacy and side effects battle for supremacy in patients, she said, “and you don’t know which is going to win out.”
Kicking Traditional Therapy to the Curb
There are many possible side effects from steroids, she said, including steroid-induced diabetes, which is “profound.” Some patients never recover from it.
On top of all these risks, she said, 20%-30% of patients are resistant to steroids.
As for other treatments, immune globulin and plasmapheresis “aren’t really benign,” Guidon said. They come with potentially serious side effects of their own, as do nonsteroidal immunosuppressive treatments.
Guidon said better treatments are needed to minimize the risks from traditional therapies. “We need targeted therapies that drive disease into remission, can be tapered, are delivered orally or with infrequent self-injections, and don’t require frequent lab monitoring.”
In addition, ideal treatments should “have a good safety data in pregnancy and for breastfeeding and have a favorable side effect profile with no significant long-term cancer risks.”
Claytor had no disclosures. Guidon disclosed consulting/medical advisory board (Alexion Pharmaceuticals, argenx, Regeneron, and UCB), publishing royalties (Oakstone), and other research support (Myasthenia Gravis Foundation of America, Myasthenia Gravis Rare Disease Network, National Institutes of Health, and National Institute of Neurological Disorders and Stroke/BioSensics).
A version of this article appeared on Medscape.com.
SAVANNAH, GEORGIA —
In a debate at American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) 2024, a pair of neurologists who specialize in neuromuscular disorders laid out opposing evidence for each approach.
On one hand, Benjamin Claytor, MD, of Cleveland Clinic, Cleveland, argued that “traditional therapy is very effective for the majority of myasthenia gravis patients,” and he said it should be considered first-line.
But Amanda C. Guidon, MD, MPH, of Massachusetts General Hospital and Harvard Medical School, both in Boston, responded that “the immunosuppression of traditional therapies is too broad: The time to benefit is too long, the burden of side effects is too high, and the cancer risk is too elevated.”
Traditional Therapy: Affordable, Tolerable, and Safe?
Claytor said ideal myasthenia gravis therapies are effective, tolerable, and safe. They’re also affordable, convenient (such as a pill), lead to sustained remission, and can have dosages reduced.
Only traditional therapies — corticosteroids, azathioprine, mycophenolate, and rituximab — meet those last three criteria, he said. Newer therapies, he said, do not.
Claytor highlighted a 2023 Duke University study that tracked 367 patients with MG who were treated with traditional therapies after the year 2000. Of those, 72% reached the treatment goal of minimal manifestations in a median of less than 2 years.
In addition, Claytor noted that the percentage of patients with myasthenia gravis who reach minimal symptom expression ranges from 45% (6 months) to 60% or more (2 years), while studies suggest that newer treatments such as eculizumab (Soliris), efgartigimod (Vyvgart), rozanolixizumab (Rystiggo), and zilucoplan (Zilbrysq) haven’t reached those levels.
As for specific traditional therapies, Claytor said the corticosteroid prednisone is “extremely affordable,” effective, and takes fewer than 2 weeks to work. All patients with myasthenia gravis can take it, he said, and at least 75% of those with mild/moderate disease respond to low doses.
Nonsteroidal Agents, Immune Globulin, Rituximab
He acknowledged side effects from corticosteroids but said doses can be tapered once severity improves. Calcium and vitamin D can be helpful to support bone health, he added.
As for nonsteroidal immunosuppressive treatments, he said they’re easy to administer, increase the likelihood of reaching minimal manifestation status, can be effective at lower doses, and may allow patients to discontinue steroids.
Two other traditional therapies, immune globulin and plasmapheresis, can be appropriate in crisis or impending crisis situations, he said, or as an add-on therapy if steroids and nonsteroidal immunosuppressive therapies don’t work.
What about rituximab? “We’re learning that patients with new-onset disease and younger patients seem to respond better,” Claytor said. While rituximab is expensive, it’s “not even in the same realm” as newer agents if only a dose or two are given, he said.
Steroids Are Ideal in MG? Not So Fast
In her response, Guidon noted that she was assigned to offer a counter-perspective in her presentation, and “personal opinions are not being represented here fully.” She then listed the weaknesses of traditional therapy in myasthenia gravis.
For one thing, she said the drugs don’t work well. She highlighted a 2019 registry study that found “many myasthenia gravis patients remain negatively impacted despite treatment.”
In addition, “we can’t predict who will respond to which therapy. ... We start drugs and don’t know if we’ll have benefit from 6 months up to 18 months. We also can’t determine minimally effective dose a priori. Some patients require higher doses, and some subtherapeutic doses are actually therapeutic for our patients.”
Broad immunosuppression, she added, boosts the risk for serious infections. “We’ve all heard from our patients that the side effects can be worse than the myasthenia, and next we’re going to talk about the role of corticosteroids in myasthenia.”
As for corticosteroids in particular, “they’re really the best treatment and also the worst treatment.” Efficacy and side effects battle for supremacy in patients, she said, “and you don’t know which is going to win out.”
Kicking Traditional Therapy to the Curb
There are many possible side effects from steroids, she said, including steroid-induced diabetes, which is “profound.” Some patients never recover from it.
On top of all these risks, she said, 20%-30% of patients are resistant to steroids.
As for other treatments, immune globulin and plasmapheresis “aren’t really benign,” Guidon said. They come with potentially serious side effects of their own, as do nonsteroidal immunosuppressive treatments.
Guidon said better treatments are needed to minimize the risks from traditional therapies. “We need targeted therapies that drive disease into remission, can be tapered, are delivered orally or with infrequent self-injections, and don’t require frequent lab monitoring.”
In addition, ideal treatments should “have a good safety data in pregnancy and for breastfeeding and have a favorable side effect profile with no significant long-term cancer risks.”
Claytor had no disclosures. Guidon disclosed consulting/medical advisory board (Alexion Pharmaceuticals, argenx, Regeneron, and UCB), publishing royalties (Oakstone), and other research support (Myasthenia Gravis Foundation of America, Myasthenia Gravis Rare Disease Network, National Institutes of Health, and National Institute of Neurological Disorders and Stroke/BioSensics).
A version of this article appeared on Medscape.com.
FROM AANEM 2024
New Drug Options Abound for Duchenne Muscular Dystrophy
SAVANNAH, GEORGIA — When Ann & Robert H. Lurie Children’s Hospital of Chicago pediatric neurologist Nancy L. Kuntz, MD, was a fellow about 45 years ago, there were few more devastating diagnoses than Duchenne muscular dystrophy (DMD).
“The rule of thumb was that they would stop walking by age 10 and probably die around age 20, and there was not much we could do,” Kuntz told colleagues at the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) 2024.
Now, “In the last 8 years, we’ve seen eight different therapies that are FDA-approved specifically for Duchenne, and many more are in the pipeline,” said session moderator Kathryn Mosher, MD, a pediatric physical medicine and rehabilitation physician at Akron Children’s Hospital, Akron, Ohio.
This is both good news and a new challenge for clinicians: Which of these treatments are best for which patients? Kuntz said the traditional therapy of corticosteroids is still crucial. However, “there are still families begging to not use steroids, or refusing to use steroids, just not filling the prescriptions,” she said.
Beware of Parents Who Reject Steroids
The failure to use steroids “breaks your heart” because data show their impact on “really important functions like walking and being able to get up from the ground,” she said. “You can add months and years to life with this treatment.”
However, “while we have shown that using corticosteroids makes a difference, I don’t think that we’ve really worked out the best age at which to start the steroids, or the dosing schedule, or even the type of steroids,” she cautioned.
In an accompanying presentation about therapy for DMD, pediatric neurologist Craig M. Zaidman, MD, of Washington University in St. Louis, Missouri, cautioned that “daily steroids make a big impact on your growth and particularly on your height.”
In particular, the corticosteroid deflazacort has been linked to more cataracts than prednisone and less weight gain and height growth. “They really don’t grow, they don’t get taller, and they also don’t gain weight. They look like little boys when they’re 13 years old.”
Deflazacort or Vamorolone?
Vamorolone (Agamree) is a cheaper corticosteroid alternative to deflazacort (Emflaza), and a 2024 study showed no difference in functional outcomes over 48 weeks, he said. Also, daily vamorolone does a better job of preserving height growth than daily prednisone, he said, and he’s seen less risk for vertebral fractures.
Where do newer drugs fit in? One crucial thing to know about the new generation of targeted therapies is that they’re often mutation-dependent, Kuntz said. They may only work in patients with certain mutations, or mutations may lead to more side effects.
“You should have the exact mutation of your patient, and then you can look and see what they’re eligible for,” she said.
$700,000 a Year for Givinostat
Zaidman highlighted the newly approved givinostat (Duvyzat), a histone deacetylase inhibitor approved for boys 6 years or older. The cost is $700,000 a year, he said, and it’s been linked to less decline in four-stair climb per a double-blind, placebo-controlled, phase 3 trial.
The drug can cause side effects such as reducing platelets, boosting triglycerides, and inducing gastrointestinal problems. “When you drop the dose, these problems go away,” he said.
Does givinostat work? While trial data are challenging to interpret, they do suggest that patients “will lose skill, but they might not lose two or three skills they otherwise would have,” Zaidman said. “To me, that’s quite compelling.”
As for exon-skipping therapies, another new-generation option for DMD, he noted that “these drugs are on the market based on their accelerated approval. We will never have the perfect phase 3, randomized, controlled, long-term trial for these. It’s just not going to come. This is what we get.”
Mosher disclosed the advisory board (Sarepta Therapeutics, Pfizer, Reata Pharmaceuticals, and PTC). Kuntz disclosed advisory board (Astellas Pharma, Inc., argenx, Catalyst, Entrada Therapeutics, Genentech, and Novartis), exchange expert on-demand program (Sarepta Therapeutics), speaker (Genentech, Sarepta Therapeutics, and Solid), and research funding (Astellas Pharma, Inc., argenx, Biogen, Catalyst, Genentech, Novartis, and Sarepta Therapeutics). Zaidman disclosed speaking/advisor/consulting (Sarepta Therapeutics and Optum) and research funding (Novartis and Biogen).
A version of this article appeared on Medscape.com.
SAVANNAH, GEORGIA — When Ann & Robert H. Lurie Children’s Hospital of Chicago pediatric neurologist Nancy L. Kuntz, MD, was a fellow about 45 years ago, there were few more devastating diagnoses than Duchenne muscular dystrophy (DMD).
“The rule of thumb was that they would stop walking by age 10 and probably die around age 20, and there was not much we could do,” Kuntz told colleagues at the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) 2024.
Now, “In the last 8 years, we’ve seen eight different therapies that are FDA-approved specifically for Duchenne, and many more are in the pipeline,” said session moderator Kathryn Mosher, MD, a pediatric physical medicine and rehabilitation physician at Akron Children’s Hospital, Akron, Ohio.
This is both good news and a new challenge for clinicians: Which of these treatments are best for which patients? Kuntz said the traditional therapy of corticosteroids is still crucial. However, “there are still families begging to not use steroids, or refusing to use steroids, just not filling the prescriptions,” she said.
Beware of Parents Who Reject Steroids
The failure to use steroids “breaks your heart” because data show their impact on “really important functions like walking and being able to get up from the ground,” she said. “You can add months and years to life with this treatment.”
However, “while we have shown that using corticosteroids makes a difference, I don’t think that we’ve really worked out the best age at which to start the steroids, or the dosing schedule, or even the type of steroids,” she cautioned.
In an accompanying presentation about therapy for DMD, pediatric neurologist Craig M. Zaidman, MD, of Washington University in St. Louis, Missouri, cautioned that “daily steroids make a big impact on your growth and particularly on your height.”
In particular, the corticosteroid deflazacort has been linked to more cataracts than prednisone and less weight gain and height growth. “They really don’t grow, they don’t get taller, and they also don’t gain weight. They look like little boys when they’re 13 years old.”
Deflazacort or Vamorolone?
Vamorolone (Agamree) is a cheaper corticosteroid alternative to deflazacort (Emflaza), and a 2024 study showed no difference in functional outcomes over 48 weeks, he said. Also, daily vamorolone does a better job of preserving height growth than daily prednisone, he said, and he’s seen less risk for vertebral fractures.
Where do newer drugs fit in? One crucial thing to know about the new generation of targeted therapies is that they’re often mutation-dependent, Kuntz said. They may only work in patients with certain mutations, or mutations may lead to more side effects.
“You should have the exact mutation of your patient, and then you can look and see what they’re eligible for,” she said.
$700,000 a Year for Givinostat
Zaidman highlighted the newly approved givinostat (Duvyzat), a histone deacetylase inhibitor approved for boys 6 years or older. The cost is $700,000 a year, he said, and it’s been linked to less decline in four-stair climb per a double-blind, placebo-controlled, phase 3 trial.
The drug can cause side effects such as reducing platelets, boosting triglycerides, and inducing gastrointestinal problems. “When you drop the dose, these problems go away,” he said.
Does givinostat work? While trial data are challenging to interpret, they do suggest that patients “will lose skill, but they might not lose two or three skills they otherwise would have,” Zaidman said. “To me, that’s quite compelling.”
As for exon-skipping therapies, another new-generation option for DMD, he noted that “these drugs are on the market based on their accelerated approval. We will never have the perfect phase 3, randomized, controlled, long-term trial for these. It’s just not going to come. This is what we get.”
Mosher disclosed the advisory board (Sarepta Therapeutics, Pfizer, Reata Pharmaceuticals, and PTC). Kuntz disclosed advisory board (Astellas Pharma, Inc., argenx, Catalyst, Entrada Therapeutics, Genentech, and Novartis), exchange expert on-demand program (Sarepta Therapeutics), speaker (Genentech, Sarepta Therapeutics, and Solid), and research funding (Astellas Pharma, Inc., argenx, Biogen, Catalyst, Genentech, Novartis, and Sarepta Therapeutics). Zaidman disclosed speaking/advisor/consulting (Sarepta Therapeutics and Optum) and research funding (Novartis and Biogen).
A version of this article appeared on Medscape.com.
SAVANNAH, GEORGIA — When Ann & Robert H. Lurie Children’s Hospital of Chicago pediatric neurologist Nancy L. Kuntz, MD, was a fellow about 45 years ago, there were few more devastating diagnoses than Duchenne muscular dystrophy (DMD).
“The rule of thumb was that they would stop walking by age 10 and probably die around age 20, and there was not much we could do,” Kuntz told colleagues at the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) 2024.
Now, “In the last 8 years, we’ve seen eight different therapies that are FDA-approved specifically for Duchenne, and many more are in the pipeline,” said session moderator Kathryn Mosher, MD, a pediatric physical medicine and rehabilitation physician at Akron Children’s Hospital, Akron, Ohio.
This is both good news and a new challenge for clinicians: Which of these treatments are best for which patients? Kuntz said the traditional therapy of corticosteroids is still crucial. However, “there are still families begging to not use steroids, or refusing to use steroids, just not filling the prescriptions,” she said.
Beware of Parents Who Reject Steroids
The failure to use steroids “breaks your heart” because data show their impact on “really important functions like walking and being able to get up from the ground,” she said. “You can add months and years to life with this treatment.”
However, “while we have shown that using corticosteroids makes a difference, I don’t think that we’ve really worked out the best age at which to start the steroids, or the dosing schedule, or even the type of steroids,” she cautioned.
In an accompanying presentation about therapy for DMD, pediatric neurologist Craig M. Zaidman, MD, of Washington University in St. Louis, Missouri, cautioned that “daily steroids make a big impact on your growth and particularly on your height.”
In particular, the corticosteroid deflazacort has been linked to more cataracts than prednisone and less weight gain and height growth. “They really don’t grow, they don’t get taller, and they also don’t gain weight. They look like little boys when they’re 13 years old.”
Deflazacort or Vamorolone?
Vamorolone (Agamree) is a cheaper corticosteroid alternative to deflazacort (Emflaza), and a 2024 study showed no difference in functional outcomes over 48 weeks, he said. Also, daily vamorolone does a better job of preserving height growth than daily prednisone, he said, and he’s seen less risk for vertebral fractures.
Where do newer drugs fit in? One crucial thing to know about the new generation of targeted therapies is that they’re often mutation-dependent, Kuntz said. They may only work in patients with certain mutations, or mutations may lead to more side effects.
“You should have the exact mutation of your patient, and then you can look and see what they’re eligible for,” she said.
$700,000 a Year for Givinostat
Zaidman highlighted the newly approved givinostat (Duvyzat), a histone deacetylase inhibitor approved for boys 6 years or older. The cost is $700,000 a year, he said, and it’s been linked to less decline in four-stair climb per a double-blind, placebo-controlled, phase 3 trial.
The drug can cause side effects such as reducing platelets, boosting triglycerides, and inducing gastrointestinal problems. “When you drop the dose, these problems go away,” he said.
Does givinostat work? While trial data are challenging to interpret, they do suggest that patients “will lose skill, but they might not lose two or three skills they otherwise would have,” Zaidman said. “To me, that’s quite compelling.”
As for exon-skipping therapies, another new-generation option for DMD, he noted that “these drugs are on the market based on their accelerated approval. We will never have the perfect phase 3, randomized, controlled, long-term trial for these. It’s just not going to come. This is what we get.”
Mosher disclosed the advisory board (Sarepta Therapeutics, Pfizer, Reata Pharmaceuticals, and PTC). Kuntz disclosed advisory board (Astellas Pharma, Inc., argenx, Catalyst, Entrada Therapeutics, Genentech, and Novartis), exchange expert on-demand program (Sarepta Therapeutics), speaker (Genentech, Sarepta Therapeutics, and Solid), and research funding (Astellas Pharma, Inc., argenx, Biogen, Catalyst, Genentech, Novartis, and Sarepta Therapeutics). Zaidman disclosed speaking/advisor/consulting (Sarepta Therapeutics and Optum) and research funding (Novartis and Biogen).
A version of this article appeared on Medscape.com.
FROM AANEM 2024
Study Finds Link to Increased Risk for Bulimia, Binge Eating and HS
“Clinicians should actively screen for eating disorders,” particularly bulimia nervosa and binge eating disorder, in patients with HS,” lead study author Christopher Guirguis, DMD, a student at Georgetown University School of Medicine, Washington, DC, told this news organization in advance of the annual Symposium on Hidradenitis Suppurative Advances, where the study was presented during an oral abstract session. “The significant psychological burden in these patients requires a holistic approach that integrates both dermatologic and psychosocial care. Addressing their mental health needs is essential for improving overall patient outcomes and quality of life,” he added.
In collaboration with fellow Georgetown medical student and first author Lauren Chin and Mikael Horissian, MD, a dermatologist and director of the HS Clinic at Gesinger Health System, Danville, Pennsylvania, Guirguis drew from the National Institutes of Health’s All of Us Research Program to identify 1653 individuals with a diagnosis of HS and a control group of 8265 individuals without a diagnosis of HS. They used the Observational Medical Outcomes Partnership to identify anorexia nervosa, bulimia nervosa, body dysmorphic disorder, binge eating disorder, and eating disorder, unspecified. Obsessive-compulsive disorder (OCD) was also included because of its association with bulimia. They used statistical models to compare cohorts and comorbidities. “What makes this work unique is its focus on the link between HS and eating disorders, a relationship previously underexplored,” he said.
The mean age of the overall study cohort was 46.8 years, and 78.6% were female. Univariate analysis revealed that, compared with controls, individuals in the HS cohort showed significantly increased diagnoses of bulimia, binge eating disorder, OCD, and eating disorder, unspecified, by 2.6, 5.48, 2.50, and 2.43 times, respectively (P < .05 for all associations). After adjusting for age, race, sex, and ethnicity, the researchers observed that patients with HS were 4.46 times as likely to have a diagnosis of binge eating disorder and 3.51 times as likely to have a diagnosis of bulimia as those who did not have HS (P < .05 for both associations).
Guirguis said that the absence of body dysmorphic disorder diagnoses in the HS cohort was unexpected. “Given HS’s known association with body image issues, we anticipated a higher prevalence of BDD,” he said. “This discrepancy may reflect underreporting or diagnostic overshadowing, where the physical symptoms of HS dominate clinical attention, potentially masking or complicating the identification of psychological conditions like BDD.”
He acknowledged certain limitations of the study, including the potential for variations in documentation practices in the database. “Additionally, there may be bias due to underrepresentation of certain demographic groups or underreporting of psychological comorbidities, which could influence the findings.”
Patricia M. Richey, MD, assistant professor of dermatology, at Boston University School of Medicine in Massachusetts, who was asked to comment on the study, said the results “should affect how physicians discuss lifestyle recommendations in those already at increased risk of psychiatric disease and disrupted body image.” The findings should also “prompt physicians to screen this patient population more thoroughly for eating disorders as we know they are an underrecognized and often undertreated entity,” she added.
Neither the study authors nor Richey reported having relevant disclosures.
A version of this article appeared on Medscape.com.
“Clinicians should actively screen for eating disorders,” particularly bulimia nervosa and binge eating disorder, in patients with HS,” lead study author Christopher Guirguis, DMD, a student at Georgetown University School of Medicine, Washington, DC, told this news organization in advance of the annual Symposium on Hidradenitis Suppurative Advances, where the study was presented during an oral abstract session. “The significant psychological burden in these patients requires a holistic approach that integrates both dermatologic and psychosocial care. Addressing their mental health needs is essential for improving overall patient outcomes and quality of life,” he added.
In collaboration with fellow Georgetown medical student and first author Lauren Chin and Mikael Horissian, MD, a dermatologist and director of the HS Clinic at Gesinger Health System, Danville, Pennsylvania, Guirguis drew from the National Institutes of Health’s All of Us Research Program to identify 1653 individuals with a diagnosis of HS and a control group of 8265 individuals without a diagnosis of HS. They used the Observational Medical Outcomes Partnership to identify anorexia nervosa, bulimia nervosa, body dysmorphic disorder, binge eating disorder, and eating disorder, unspecified. Obsessive-compulsive disorder (OCD) was also included because of its association with bulimia. They used statistical models to compare cohorts and comorbidities. “What makes this work unique is its focus on the link between HS and eating disorders, a relationship previously underexplored,” he said.
The mean age of the overall study cohort was 46.8 years, and 78.6% were female. Univariate analysis revealed that, compared with controls, individuals in the HS cohort showed significantly increased diagnoses of bulimia, binge eating disorder, OCD, and eating disorder, unspecified, by 2.6, 5.48, 2.50, and 2.43 times, respectively (P < .05 for all associations). After adjusting for age, race, sex, and ethnicity, the researchers observed that patients with HS were 4.46 times as likely to have a diagnosis of binge eating disorder and 3.51 times as likely to have a diagnosis of bulimia as those who did not have HS (P < .05 for both associations).
Guirguis said that the absence of body dysmorphic disorder diagnoses in the HS cohort was unexpected. “Given HS’s known association with body image issues, we anticipated a higher prevalence of BDD,” he said. “This discrepancy may reflect underreporting or diagnostic overshadowing, where the physical symptoms of HS dominate clinical attention, potentially masking or complicating the identification of psychological conditions like BDD.”
He acknowledged certain limitations of the study, including the potential for variations in documentation practices in the database. “Additionally, there may be bias due to underrepresentation of certain demographic groups or underreporting of psychological comorbidities, which could influence the findings.”
Patricia M. Richey, MD, assistant professor of dermatology, at Boston University School of Medicine in Massachusetts, who was asked to comment on the study, said the results “should affect how physicians discuss lifestyle recommendations in those already at increased risk of psychiatric disease and disrupted body image.” The findings should also “prompt physicians to screen this patient population more thoroughly for eating disorders as we know they are an underrecognized and often undertreated entity,” she added.
Neither the study authors nor Richey reported having relevant disclosures.
A version of this article appeared on Medscape.com.
“Clinicians should actively screen for eating disorders,” particularly bulimia nervosa and binge eating disorder, in patients with HS,” lead study author Christopher Guirguis, DMD, a student at Georgetown University School of Medicine, Washington, DC, told this news organization in advance of the annual Symposium on Hidradenitis Suppurative Advances, where the study was presented during an oral abstract session. “The significant psychological burden in these patients requires a holistic approach that integrates both dermatologic and psychosocial care. Addressing their mental health needs is essential for improving overall patient outcomes and quality of life,” he added.
In collaboration with fellow Georgetown medical student and first author Lauren Chin and Mikael Horissian, MD, a dermatologist and director of the HS Clinic at Gesinger Health System, Danville, Pennsylvania, Guirguis drew from the National Institutes of Health’s All of Us Research Program to identify 1653 individuals with a diagnosis of HS and a control group of 8265 individuals without a diagnosis of HS. They used the Observational Medical Outcomes Partnership to identify anorexia nervosa, bulimia nervosa, body dysmorphic disorder, binge eating disorder, and eating disorder, unspecified. Obsessive-compulsive disorder (OCD) was also included because of its association with bulimia. They used statistical models to compare cohorts and comorbidities. “What makes this work unique is its focus on the link between HS and eating disorders, a relationship previously underexplored,” he said.
The mean age of the overall study cohort was 46.8 years, and 78.6% were female. Univariate analysis revealed that, compared with controls, individuals in the HS cohort showed significantly increased diagnoses of bulimia, binge eating disorder, OCD, and eating disorder, unspecified, by 2.6, 5.48, 2.50, and 2.43 times, respectively (P < .05 for all associations). After adjusting for age, race, sex, and ethnicity, the researchers observed that patients with HS were 4.46 times as likely to have a diagnosis of binge eating disorder and 3.51 times as likely to have a diagnosis of bulimia as those who did not have HS (P < .05 for both associations).
Guirguis said that the absence of body dysmorphic disorder diagnoses in the HS cohort was unexpected. “Given HS’s known association with body image issues, we anticipated a higher prevalence of BDD,” he said. “This discrepancy may reflect underreporting or diagnostic overshadowing, where the physical symptoms of HS dominate clinical attention, potentially masking or complicating the identification of psychological conditions like BDD.”
He acknowledged certain limitations of the study, including the potential for variations in documentation practices in the database. “Additionally, there may be bias due to underrepresentation of certain demographic groups or underreporting of psychological comorbidities, which could influence the findings.”
Patricia M. Richey, MD, assistant professor of dermatology, at Boston University School of Medicine in Massachusetts, who was asked to comment on the study, said the results “should affect how physicians discuss lifestyle recommendations in those already at increased risk of psychiatric disease and disrupted body image.” The findings should also “prompt physicians to screen this patient population more thoroughly for eating disorders as we know they are an underrecognized and often undertreated entity,” she added.
Neither the study authors nor Richey reported having relevant disclosures.
A version of this article appeared on Medscape.com.
Guselkumab Efficacy in Crohn’s Disease Unaffected by Prior Biologic Use
VIENNA — according to a pooled analysis of the two phase 3 double-blind GALAXI 2 and 3 studies.
“We found that guselkumab was effective in both biologic-naive and biologic-inadequate subpopulations,” said coinvestigator Bruce E. Sands, MD, AGAF, gastroenterologist from Icahn School of Medicine at Mount Sinai, New York City.
These latest results add to the primary results of these studies reported earlier in 2024 that guselkumab was shown to be superior to both placebo and ustekinumab in the same patient population with moderately to severely active CD.
Sands reported the new data in a presentation at the United European Gastroenterology (UEG) Week 2024.
Guselkumab potently blocks interleukin (IL)–23 and binds to CD64, a receptor on cells that produce IL-23. The dual-acting IL-23p19 subunit inhibitor agent is currently under review by the Food and Drug Administration (FDA) for moderately to severely active CD. In September, guselkumab (Tremfya, Johnson & Johnson) was approved for use in moderately to severely active ulcerative colitis.
GALAXI 2 and 3 Pooled Dataset
In the two independent, identically designed GALAXI 2 and 3 studies, patients were randomized to guselkumab treatment at either 200 mg intravenous (IV) induction at weeks 0, 4, and 8, followed by 200 mg subcutaneous maintenance every 4 weeks, starting at week 12, or 200 mg IV induction at weeks 0, 4, and 8, followed by 100 mg subcutaneous maintenance every 8 weeks, starting at week 16; or to ustekinumab; or to placebo.
Participants were required to remain on their treatment of initial randomization for a long-term extension study (up to 5 years) looking at clinical, endoscopic, and safety outcomes, except for participants on placebo who were allowed to switch to ustekinumab if clinical response was not met at week 12.
Inclusion criteria for the studies comprised a Crohn’s Disease Activity Index score between 220 and 450, a mean daily stool frequency count > 3 or an abdominal pain score > 1, and a simple endoscopic score for CD score ≥ 6. Participants were also required to have shown an inadequate response or intolerance to oral corticosteroids, 6-mercaptopurine/azathioprine/methotrexate, or biologic therapies.
The pooled dataset included patients on either dose of guselkumab and patients on placebo (total n = 730). Of these, 52% of participants had shown a prior inadequate response to a biologic, 42% were biologic naive, and 6% had prior exposure to biologics but no documented failure. Patients on ustekinumab were not included in this analysis.
Almost all patients (97%) in the biologic-inadequate response group had previously received at least one anti–tumor necrosis factor agent, and around 15% had received vedolizumab. As expected, the biologic-inadequate responders were a lot sicker than the biologic-naive patients, Sands reported.
The composite co–primary endpoints for each guselkumab regimen vs placebo were clinical response at week 12 plus clinical remission at week 48, and clinical response at week 12 plus endoscopic response at week 48.
The major secondary endpoints comprised clinical remission at week 12 and endoscopic response also at week 12.
Short- and Long-Term Endpoints in Both Subgroups
In the biologic-naive subgroup, 54.7% of patients receiving the 200-mg dose regimen of guselkumab and 51.7% of those receiving the 100-mg dose regimen showed a clinical response at week 12 plus clinical remission at week 48, compared with 11.5% in the placebo group (P < .001 for both compared with placebo).
In the biologic-inadequate response group, 49.7% of those receiving the 200-mg dose regimen of guselkumab and 45.8% on the 100-mg dose regimen reached the composite endpoint, compared with the placebo response of 12.8% (P < .001 for both compared with placebo).
“You can see a slight decrease in response in the biologic-inadequate responders, but on the whole, the confidence intervals are highly overlapping,” said Sands.
Turning to major secondary endpoints at week 12, clinical remission was reached by 49.6% of the biologic-naive group on the 200-mg guselkumab regimen vs 16.4% on placebo, and by 46.0% of the biologic-inadequate group on the 200-mg regimen vs 19.2% on placebo (P < .001 for both subgroups). Endoscopic response was achieved by 46.3% of patients in the biologic-naive group and 29.0% in the biologic-inadequate group on the 200-mg regimen vs 18.0% and 6.4%, respectively, on placebo (P < .001 for both subgroups).
Sands noted that the drug has an excellent safety profile.
“These data show the drug works for naive patients who have failed conventional therapies, as well as for those who have failed biologic therapies,” so it could be used as a first- or second-line biologic, he added.
Sands reported potential conflicts of interest with AbbVie, Abivax, Adiso Therapeutics, Agomab, Alimentiv, Amgen, AnaptysBio, Arena Pharmaceuticals, Artugen Therapeutics, AstraZeneca, Biora Therapeutics, Boehringer Ingelheim, Boston Pharmaceuticals, Bristol-Myers Squibb, Calibr, Celgene, Celltrion, ClostraBio, Equillium, Enthera, Evommune, Ferring, Fresenius Kabi, Galapagos, Genentech (Roche), Gilead Sciences, GlaxoSmithKline, Gossamer Bio, Index Pharmaceuticals, Innovation Pharmaceuticals, Inotrem, Janssen, Kaleido, Kallyope, Lilly, Merck, Microbiotica, Mobius Care, Morphic Therapeutic, MRM Health, Pfizer, Nexus Therapeutics, Nimbus Discovery, Odyssey Therapeutics, Progenity, Prometheus Biosciences, Prometheus Laboratories, Protagonist Therapeutics, Q32 Bio, Rasayana Therapeutics, Recludix Pharma, Reistone Biopharma, Sun Pharma, Surrozen, Target RWE, Takeda, Teva, Theravance Biopharma, TLL Pharmaceutical, Tr1X, UNION Therapeutics, and Ventyx Biosciences.
A version of this article appeared on Medscape.com.
VIENNA — according to a pooled analysis of the two phase 3 double-blind GALAXI 2 and 3 studies.
“We found that guselkumab was effective in both biologic-naive and biologic-inadequate subpopulations,” said coinvestigator Bruce E. Sands, MD, AGAF, gastroenterologist from Icahn School of Medicine at Mount Sinai, New York City.
These latest results add to the primary results of these studies reported earlier in 2024 that guselkumab was shown to be superior to both placebo and ustekinumab in the same patient population with moderately to severely active CD.
Sands reported the new data in a presentation at the United European Gastroenterology (UEG) Week 2024.
Guselkumab potently blocks interleukin (IL)–23 and binds to CD64, a receptor on cells that produce IL-23. The dual-acting IL-23p19 subunit inhibitor agent is currently under review by the Food and Drug Administration (FDA) for moderately to severely active CD. In September, guselkumab (Tremfya, Johnson & Johnson) was approved for use in moderately to severely active ulcerative colitis.
GALAXI 2 and 3 Pooled Dataset
In the two independent, identically designed GALAXI 2 and 3 studies, patients were randomized to guselkumab treatment at either 200 mg intravenous (IV) induction at weeks 0, 4, and 8, followed by 200 mg subcutaneous maintenance every 4 weeks, starting at week 12, or 200 mg IV induction at weeks 0, 4, and 8, followed by 100 mg subcutaneous maintenance every 8 weeks, starting at week 16; or to ustekinumab; or to placebo.
Participants were required to remain on their treatment of initial randomization for a long-term extension study (up to 5 years) looking at clinical, endoscopic, and safety outcomes, except for participants on placebo who were allowed to switch to ustekinumab if clinical response was not met at week 12.
Inclusion criteria for the studies comprised a Crohn’s Disease Activity Index score between 220 and 450, a mean daily stool frequency count > 3 or an abdominal pain score > 1, and a simple endoscopic score for CD score ≥ 6. Participants were also required to have shown an inadequate response or intolerance to oral corticosteroids, 6-mercaptopurine/azathioprine/methotrexate, or biologic therapies.
The pooled dataset included patients on either dose of guselkumab and patients on placebo (total n = 730). Of these, 52% of participants had shown a prior inadequate response to a biologic, 42% were biologic naive, and 6% had prior exposure to biologics but no documented failure. Patients on ustekinumab were not included in this analysis.
Almost all patients (97%) in the biologic-inadequate response group had previously received at least one anti–tumor necrosis factor agent, and around 15% had received vedolizumab. As expected, the biologic-inadequate responders were a lot sicker than the biologic-naive patients, Sands reported.
The composite co–primary endpoints for each guselkumab regimen vs placebo were clinical response at week 12 plus clinical remission at week 48, and clinical response at week 12 plus endoscopic response at week 48.
The major secondary endpoints comprised clinical remission at week 12 and endoscopic response also at week 12.
Short- and Long-Term Endpoints in Both Subgroups
In the biologic-naive subgroup, 54.7% of patients receiving the 200-mg dose regimen of guselkumab and 51.7% of those receiving the 100-mg dose regimen showed a clinical response at week 12 plus clinical remission at week 48, compared with 11.5% in the placebo group (P < .001 for both compared with placebo).
In the biologic-inadequate response group, 49.7% of those receiving the 200-mg dose regimen of guselkumab and 45.8% on the 100-mg dose regimen reached the composite endpoint, compared with the placebo response of 12.8% (P < .001 for both compared with placebo).
“You can see a slight decrease in response in the biologic-inadequate responders, but on the whole, the confidence intervals are highly overlapping,” said Sands.
Turning to major secondary endpoints at week 12, clinical remission was reached by 49.6% of the biologic-naive group on the 200-mg guselkumab regimen vs 16.4% on placebo, and by 46.0% of the biologic-inadequate group on the 200-mg regimen vs 19.2% on placebo (P < .001 for both subgroups). Endoscopic response was achieved by 46.3% of patients in the biologic-naive group and 29.0% in the biologic-inadequate group on the 200-mg regimen vs 18.0% and 6.4%, respectively, on placebo (P < .001 for both subgroups).
Sands noted that the drug has an excellent safety profile.
“These data show the drug works for naive patients who have failed conventional therapies, as well as for those who have failed biologic therapies,” so it could be used as a first- or second-line biologic, he added.
Sands reported potential conflicts of interest with AbbVie, Abivax, Adiso Therapeutics, Agomab, Alimentiv, Amgen, AnaptysBio, Arena Pharmaceuticals, Artugen Therapeutics, AstraZeneca, Biora Therapeutics, Boehringer Ingelheim, Boston Pharmaceuticals, Bristol-Myers Squibb, Calibr, Celgene, Celltrion, ClostraBio, Equillium, Enthera, Evommune, Ferring, Fresenius Kabi, Galapagos, Genentech (Roche), Gilead Sciences, GlaxoSmithKline, Gossamer Bio, Index Pharmaceuticals, Innovation Pharmaceuticals, Inotrem, Janssen, Kaleido, Kallyope, Lilly, Merck, Microbiotica, Mobius Care, Morphic Therapeutic, MRM Health, Pfizer, Nexus Therapeutics, Nimbus Discovery, Odyssey Therapeutics, Progenity, Prometheus Biosciences, Prometheus Laboratories, Protagonist Therapeutics, Q32 Bio, Rasayana Therapeutics, Recludix Pharma, Reistone Biopharma, Sun Pharma, Surrozen, Target RWE, Takeda, Teva, Theravance Biopharma, TLL Pharmaceutical, Tr1X, UNION Therapeutics, and Ventyx Biosciences.
A version of this article appeared on Medscape.com.
VIENNA — according to a pooled analysis of the two phase 3 double-blind GALAXI 2 and 3 studies.
“We found that guselkumab was effective in both biologic-naive and biologic-inadequate subpopulations,” said coinvestigator Bruce E. Sands, MD, AGAF, gastroenterologist from Icahn School of Medicine at Mount Sinai, New York City.
These latest results add to the primary results of these studies reported earlier in 2024 that guselkumab was shown to be superior to both placebo and ustekinumab in the same patient population with moderately to severely active CD.
Sands reported the new data in a presentation at the United European Gastroenterology (UEG) Week 2024.
Guselkumab potently blocks interleukin (IL)–23 and binds to CD64, a receptor on cells that produce IL-23. The dual-acting IL-23p19 subunit inhibitor agent is currently under review by the Food and Drug Administration (FDA) for moderately to severely active CD. In September, guselkumab (Tremfya, Johnson & Johnson) was approved for use in moderately to severely active ulcerative colitis.
GALAXI 2 and 3 Pooled Dataset
In the two independent, identically designed GALAXI 2 and 3 studies, patients were randomized to guselkumab treatment at either 200 mg intravenous (IV) induction at weeks 0, 4, and 8, followed by 200 mg subcutaneous maintenance every 4 weeks, starting at week 12, or 200 mg IV induction at weeks 0, 4, and 8, followed by 100 mg subcutaneous maintenance every 8 weeks, starting at week 16; or to ustekinumab; or to placebo.
Participants were required to remain on their treatment of initial randomization for a long-term extension study (up to 5 years) looking at clinical, endoscopic, and safety outcomes, except for participants on placebo who were allowed to switch to ustekinumab if clinical response was not met at week 12.
Inclusion criteria for the studies comprised a Crohn’s Disease Activity Index score between 220 and 450, a mean daily stool frequency count > 3 or an abdominal pain score > 1, and a simple endoscopic score for CD score ≥ 6. Participants were also required to have shown an inadequate response or intolerance to oral corticosteroids, 6-mercaptopurine/azathioprine/methotrexate, or biologic therapies.
The pooled dataset included patients on either dose of guselkumab and patients on placebo (total n = 730). Of these, 52% of participants had shown a prior inadequate response to a biologic, 42% were biologic naive, and 6% had prior exposure to biologics but no documented failure. Patients on ustekinumab were not included in this analysis.
Almost all patients (97%) in the biologic-inadequate response group had previously received at least one anti–tumor necrosis factor agent, and around 15% had received vedolizumab. As expected, the biologic-inadequate responders were a lot sicker than the biologic-naive patients, Sands reported.
The composite co–primary endpoints for each guselkumab regimen vs placebo were clinical response at week 12 plus clinical remission at week 48, and clinical response at week 12 plus endoscopic response at week 48.
The major secondary endpoints comprised clinical remission at week 12 and endoscopic response also at week 12.
Short- and Long-Term Endpoints in Both Subgroups
In the biologic-naive subgroup, 54.7% of patients receiving the 200-mg dose regimen of guselkumab and 51.7% of those receiving the 100-mg dose regimen showed a clinical response at week 12 plus clinical remission at week 48, compared with 11.5% in the placebo group (P < .001 for both compared with placebo).
In the biologic-inadequate response group, 49.7% of those receiving the 200-mg dose regimen of guselkumab and 45.8% on the 100-mg dose regimen reached the composite endpoint, compared with the placebo response of 12.8% (P < .001 for both compared with placebo).
“You can see a slight decrease in response in the biologic-inadequate responders, but on the whole, the confidence intervals are highly overlapping,” said Sands.
Turning to major secondary endpoints at week 12, clinical remission was reached by 49.6% of the biologic-naive group on the 200-mg guselkumab regimen vs 16.4% on placebo, and by 46.0% of the biologic-inadequate group on the 200-mg regimen vs 19.2% on placebo (P < .001 for both subgroups). Endoscopic response was achieved by 46.3% of patients in the biologic-naive group and 29.0% in the biologic-inadequate group on the 200-mg regimen vs 18.0% and 6.4%, respectively, on placebo (P < .001 for both subgroups).
Sands noted that the drug has an excellent safety profile.
“These data show the drug works for naive patients who have failed conventional therapies, as well as for those who have failed biologic therapies,” so it could be used as a first- or second-line biologic, he added.
Sands reported potential conflicts of interest with AbbVie, Abivax, Adiso Therapeutics, Agomab, Alimentiv, Amgen, AnaptysBio, Arena Pharmaceuticals, Artugen Therapeutics, AstraZeneca, Biora Therapeutics, Boehringer Ingelheim, Boston Pharmaceuticals, Bristol-Myers Squibb, Calibr, Celgene, Celltrion, ClostraBio, Equillium, Enthera, Evommune, Ferring, Fresenius Kabi, Galapagos, Genentech (Roche), Gilead Sciences, GlaxoSmithKline, Gossamer Bio, Index Pharmaceuticals, Innovation Pharmaceuticals, Inotrem, Janssen, Kaleido, Kallyope, Lilly, Merck, Microbiotica, Mobius Care, Morphic Therapeutic, MRM Health, Pfizer, Nexus Therapeutics, Nimbus Discovery, Odyssey Therapeutics, Progenity, Prometheus Biosciences, Prometheus Laboratories, Protagonist Therapeutics, Q32 Bio, Rasayana Therapeutics, Recludix Pharma, Reistone Biopharma, Sun Pharma, Surrozen, Target RWE, Takeda, Teva, Theravance Biopharma, TLL Pharmaceutical, Tr1X, UNION Therapeutics, and Ventyx Biosciences.
A version of this article appeared on Medscape.com.
FROM UEG 2024
Patients With IBD More Likely to Develop, or Have Prior, T1D
VIENNA —
Their findings showed that patients with IBD had a moderately increased risk for T1D and higher odds of having prior T1D than the general population. These bidirectional associations were partially independent of shared familial factors.
Although the absolute risk for T1D is low in patients with IBD, these findings suggest that if there are nonspecific symptoms, such as weight loss and fatigue, which are typical of T1D but not of IBD, then it might be reasonable to test for diabetes, lead researcher Jiangwei Sun, PhD, postdoctoral researcher at the Karolinska Institutet, Stockholm, Sweden, told this news organization.
“Patients with IBD and T1D also tend to have worse disease outcomes for both diseases, but these two diseases are not recognized as comorbidities in the clinical guidelines,” he said.
Anecdotally, “many clinicians believe there is a higher risk of autoimmune disease in patients with IBD but not much attention is paid to type 1 diabetes,” he added.
Sun presented the study at United European Gastroenterology (UEG) Week 2024. It was also published recently in The Lancet.
Exploring the Bidirectional Relationship
Prior research in the form of a systematic review found no association between IBD and T1D, which was surprising, Sun said. Further studies found an association between IBD and incident T1D; however, these studies did not explore bidirectionality between the two diseases.
These studies also did not take shared genetic and environmental factors into consideration, though “there is known to be familial co-aggregation of IBD and T1D based on previous findings,” he said.
In this current study, Sun and colleagues compared patients with IBD with the general population, as well as with siblings without IBD to consider the potential influence of shared genetics and earlier environmental factors.
The research used two approaches to look for a bidirectional association: A nationwide matched cohort study (IBD and incident T1D) and a case-control study (IBD and prior T1D).
The cohort study included 20,314 patients with IBD aged ≤ 28 years, who were identified between 1987 and 2017. Of these, 7277 had Crohn’s disease, 10,112 had ulcerative colitis, and 2925 had unclassified IBD. There were 99,200 individually matched reference individuals.
The case-control study included 87,001 patients with IBD (without age restriction) and 431,054 matched control individuals.
Risk ratios were calculated using an adjusted hazard ratio (aHR) of incident T1D in the cohort study and an adjusted odds ratio (aOR) of prior T1D in the case-control study.
In the cohort study, the median follow-up was 14 years. Over that time, 116 patients with IBD and 353 reference individuals developed T1D. The aHR for a patient with IBD developing T1D was 1.58 (95% CI, 1.27-1.95). For patients with ulcerative colitis, the aHR of developing T1D increased to 2.02 (95% CI, 1.51-2.70); however, the association was not found for Crohn’s disease or unclassified IBD possibly because of the sample size of these latter categories, noted Sun.
In the case-control study, Sun and colleagues identified 1018 (1.2%) patients with IBD and 3496 (0.8%) control individuals who had been previously diagnosed with T1D. Patients with IBD had higher odds of having prior T1D than those without IBD (aOR, 1.36; 95% CI, 1.26-1.46). This positive association was observed in all IBD subtypes, said Sun, who added that the sample size was larger in this analysis than in the cohort analysis.
Upon comparing patients with IBD with their siblings without IBD, analyses showed similar associations between IBD and T1D; the aHR was 1.44 (95% CI, 0.97-2.15) for developing T1D, and the aOR was 1.32 (95% CI, 1.18-1.49) for prior T1D.
That these positive associations between IBD and T1D exist even when comparing patients with IBD with their siblings without IBD suggests genetics and shared environmental factors do not fully explain the association, and that later environmental factors might play a role, said Sun.
“I’m not surprised with these results,” he added. “They make sense because we know that both IBD and T1D are immunity-related diseases and have some shared pathways.”
Commenting on the study, Tine Jess, MD, director, Center for Molecular Prediction of Inflammatory Bowel Disease, PREDICT, Aalborg University in Copenhagen, Denmark, said: “The really interesting finding here is that type 1 diabetes may precede IBD, which points toward common etiologies rather than one disease leading to the other.”
“This is in line with mounting evidence that IBD is measurable at the molecular level years prior to diagnosis,” she added.
Awareness of the bidirectional association may facilitate early detection of both conditions, Sun and his colleagues noted.
Sun reported no relevant financial relationships. Jess reported receiving consultancy fees from Ferring and Pfizer.
A version of this article appeared on Medscape.com.
VIENNA —
Their findings showed that patients with IBD had a moderately increased risk for T1D and higher odds of having prior T1D than the general population. These bidirectional associations were partially independent of shared familial factors.
Although the absolute risk for T1D is low in patients with IBD, these findings suggest that if there are nonspecific symptoms, such as weight loss and fatigue, which are typical of T1D but not of IBD, then it might be reasonable to test for diabetes, lead researcher Jiangwei Sun, PhD, postdoctoral researcher at the Karolinska Institutet, Stockholm, Sweden, told this news organization.
“Patients with IBD and T1D also tend to have worse disease outcomes for both diseases, but these two diseases are not recognized as comorbidities in the clinical guidelines,” he said.
Anecdotally, “many clinicians believe there is a higher risk of autoimmune disease in patients with IBD but not much attention is paid to type 1 diabetes,” he added.
Sun presented the study at United European Gastroenterology (UEG) Week 2024. It was also published recently in The Lancet.
Exploring the Bidirectional Relationship
Prior research in the form of a systematic review found no association between IBD and T1D, which was surprising, Sun said. Further studies found an association between IBD and incident T1D; however, these studies did not explore bidirectionality between the two diseases.
These studies also did not take shared genetic and environmental factors into consideration, though “there is known to be familial co-aggregation of IBD and T1D based on previous findings,” he said.
In this current study, Sun and colleagues compared patients with IBD with the general population, as well as with siblings without IBD to consider the potential influence of shared genetics and earlier environmental factors.
The research used two approaches to look for a bidirectional association: A nationwide matched cohort study (IBD and incident T1D) and a case-control study (IBD and prior T1D).
The cohort study included 20,314 patients with IBD aged ≤ 28 years, who were identified between 1987 and 2017. Of these, 7277 had Crohn’s disease, 10,112 had ulcerative colitis, and 2925 had unclassified IBD. There were 99,200 individually matched reference individuals.
The case-control study included 87,001 patients with IBD (without age restriction) and 431,054 matched control individuals.
Risk ratios were calculated using an adjusted hazard ratio (aHR) of incident T1D in the cohort study and an adjusted odds ratio (aOR) of prior T1D in the case-control study.
In the cohort study, the median follow-up was 14 years. Over that time, 116 patients with IBD and 353 reference individuals developed T1D. The aHR for a patient with IBD developing T1D was 1.58 (95% CI, 1.27-1.95). For patients with ulcerative colitis, the aHR of developing T1D increased to 2.02 (95% CI, 1.51-2.70); however, the association was not found for Crohn’s disease or unclassified IBD possibly because of the sample size of these latter categories, noted Sun.
In the case-control study, Sun and colleagues identified 1018 (1.2%) patients with IBD and 3496 (0.8%) control individuals who had been previously diagnosed with T1D. Patients with IBD had higher odds of having prior T1D than those without IBD (aOR, 1.36; 95% CI, 1.26-1.46). This positive association was observed in all IBD subtypes, said Sun, who added that the sample size was larger in this analysis than in the cohort analysis.
Upon comparing patients with IBD with their siblings without IBD, analyses showed similar associations between IBD and T1D; the aHR was 1.44 (95% CI, 0.97-2.15) for developing T1D, and the aOR was 1.32 (95% CI, 1.18-1.49) for prior T1D.
That these positive associations between IBD and T1D exist even when comparing patients with IBD with their siblings without IBD suggests genetics and shared environmental factors do not fully explain the association, and that later environmental factors might play a role, said Sun.
“I’m not surprised with these results,” he added. “They make sense because we know that both IBD and T1D are immunity-related diseases and have some shared pathways.”
Commenting on the study, Tine Jess, MD, director, Center for Molecular Prediction of Inflammatory Bowel Disease, PREDICT, Aalborg University in Copenhagen, Denmark, said: “The really interesting finding here is that type 1 diabetes may precede IBD, which points toward common etiologies rather than one disease leading to the other.”
“This is in line with mounting evidence that IBD is measurable at the molecular level years prior to diagnosis,” she added.
Awareness of the bidirectional association may facilitate early detection of both conditions, Sun and his colleagues noted.
Sun reported no relevant financial relationships. Jess reported receiving consultancy fees from Ferring and Pfizer.
A version of this article appeared on Medscape.com.
VIENNA —
Their findings showed that patients with IBD had a moderately increased risk for T1D and higher odds of having prior T1D than the general population. These bidirectional associations were partially independent of shared familial factors.
Although the absolute risk for T1D is low in patients with IBD, these findings suggest that if there are nonspecific symptoms, such as weight loss and fatigue, which are typical of T1D but not of IBD, then it might be reasonable to test for diabetes, lead researcher Jiangwei Sun, PhD, postdoctoral researcher at the Karolinska Institutet, Stockholm, Sweden, told this news organization.
“Patients with IBD and T1D also tend to have worse disease outcomes for both diseases, but these two diseases are not recognized as comorbidities in the clinical guidelines,” he said.
Anecdotally, “many clinicians believe there is a higher risk of autoimmune disease in patients with IBD but not much attention is paid to type 1 diabetes,” he added.
Sun presented the study at United European Gastroenterology (UEG) Week 2024. It was also published recently in The Lancet.
Exploring the Bidirectional Relationship
Prior research in the form of a systematic review found no association between IBD and T1D, which was surprising, Sun said. Further studies found an association between IBD and incident T1D; however, these studies did not explore bidirectionality between the two diseases.
These studies also did not take shared genetic and environmental factors into consideration, though “there is known to be familial co-aggregation of IBD and T1D based on previous findings,” he said.
In this current study, Sun and colleagues compared patients with IBD with the general population, as well as with siblings without IBD to consider the potential influence of shared genetics and earlier environmental factors.
The research used two approaches to look for a bidirectional association: A nationwide matched cohort study (IBD and incident T1D) and a case-control study (IBD and prior T1D).
The cohort study included 20,314 patients with IBD aged ≤ 28 years, who were identified between 1987 and 2017. Of these, 7277 had Crohn’s disease, 10,112 had ulcerative colitis, and 2925 had unclassified IBD. There were 99,200 individually matched reference individuals.
The case-control study included 87,001 patients with IBD (without age restriction) and 431,054 matched control individuals.
Risk ratios were calculated using an adjusted hazard ratio (aHR) of incident T1D in the cohort study and an adjusted odds ratio (aOR) of prior T1D in the case-control study.
In the cohort study, the median follow-up was 14 years. Over that time, 116 patients with IBD and 353 reference individuals developed T1D. The aHR for a patient with IBD developing T1D was 1.58 (95% CI, 1.27-1.95). For patients with ulcerative colitis, the aHR of developing T1D increased to 2.02 (95% CI, 1.51-2.70); however, the association was not found for Crohn’s disease or unclassified IBD possibly because of the sample size of these latter categories, noted Sun.
In the case-control study, Sun and colleagues identified 1018 (1.2%) patients with IBD and 3496 (0.8%) control individuals who had been previously diagnosed with T1D. Patients with IBD had higher odds of having prior T1D than those without IBD (aOR, 1.36; 95% CI, 1.26-1.46). This positive association was observed in all IBD subtypes, said Sun, who added that the sample size was larger in this analysis than in the cohort analysis.
Upon comparing patients with IBD with their siblings without IBD, analyses showed similar associations between IBD and T1D; the aHR was 1.44 (95% CI, 0.97-2.15) for developing T1D, and the aOR was 1.32 (95% CI, 1.18-1.49) for prior T1D.
That these positive associations between IBD and T1D exist even when comparing patients with IBD with their siblings without IBD suggests genetics and shared environmental factors do not fully explain the association, and that later environmental factors might play a role, said Sun.
“I’m not surprised with these results,” he added. “They make sense because we know that both IBD and T1D are immunity-related diseases and have some shared pathways.”
Commenting on the study, Tine Jess, MD, director, Center for Molecular Prediction of Inflammatory Bowel Disease, PREDICT, Aalborg University in Copenhagen, Denmark, said: “The really interesting finding here is that type 1 diabetes may precede IBD, which points toward common etiologies rather than one disease leading to the other.”
“This is in line with mounting evidence that IBD is measurable at the molecular level years prior to diagnosis,” she added.
Awareness of the bidirectional association may facilitate early detection of both conditions, Sun and his colleagues noted.
Sun reported no relevant financial relationships. Jess reported receiving consultancy fees from Ferring and Pfizer.
A version of this article appeared on Medscape.com.
FROM UEG 2024