xenical before and after

VANCOUVER, Canada — In contrast to some previous research, investigators found no significant correlation between common biologic and oral small molecule treatments for inflammatory bowel disease (IBD) and an increased risk of major adverse cardiovascular events (MACE).

In addition, biologics such as infliximab, adalimumab, golimumab, certolizumab, vedolizumab, natalizumab, solby medicine hat and ustekinumab did not only not increase risk but they were also linked to a significantly lower risk of major cardiovascular and thromboembolic events.

Risk reduction with biologics ranged from 15% for venous thromboembolism to 34% for myocardial infarction.

“The decrease in MACE with biologics was significant — and a bit surprising — but it correlates with the theory that by decreasing inflammation, there is a decrease in MACE,” said Miguel Regueiro, MD, chief of the Digestive Disease Institute at Cleveland Clinic, and senior author of the study.

“Our thought was that we would not see an increase in MACE and it would be equivalent between patients with IBD treated with advanced therapies and patients not treated with advanced therapies,” he told Medscape Medical News.

The findings “are consistent with some of the emerging long-term extension data from IBD clinical trials,” Regueiro reported today at the American College of Gastroenterology Annual Scientific Meeting. “And I’ll make an editorial comment for those that treat and practice in inflammatory bowel disease: I think these data continue to support, affirm, and hopefully comfort us.”

Therapies Previously Implicated in Increased MACE Risk

IBD itself is associated with increased MACE risk likely due to chronic inflammation and endothelial dysfunction, the researchers note. While biologic and small molecule therapies are effective IBD treatments, some therapies have been implicated in an increased risk for MACE.

The Oral Surveillance post-marketing safety study of tofacitinib in rheumatoid arthritis, for example, linked the agent to higher MACE and venous thromboembolism rates vs a TNF inhibitor. As a result, the FDA restricted the JAK inhibitor drug class that includes tofacitinib.

While long-term extension studies in IBD have not linked oral small molecules to increases in MACE, the sample sizes and duration of follow-up have been limited, the authors noted. For this reason, Regueiro and colleagues decided to further evaluate the potential associations in people with IBD.

The cohorts included 67,607 adults with IBD taking a biologic and another 67,607 with IBD not receiving a biologic between January 2021 and June 2023. The researchers also compared 3194 adults with IBD taking an oral small molecule treatment vs another 3194 people with IBD not receiving these medications. These large sample sizes were possible through use of TriNetX, a large US claims database that includes millions of patients.

Key Findings

The propensity matched study revealed that adults with IBD on biologics had a significantly lower risk for coronary artery disease (adjusted odds ratio [aOR], 0.69; 95% CI, 0.66 – 0.72; P < .0001), myocardial infarction (aOR, 0.66; 95% CI 0.61 – 0.72; P < .0001) or stroke (aOR, 0.71; 95% CI, 0.65 – 0.77; P < .0001) compared with IBD patients not on biological therapy.

The researchers also found a lower risk for venous thromboembolism associated with biologics (aOR, 0.85; 95% CI 0.81 – 0.89; P < .0001).

Regueiro said that active inflammation in the bowel or anywhere in the body is associated with higher rates of blood clot formation. “The thought is that decreasing inflammation with treatment may actually decrease the rates of blood clots. So, in essence, we think that biologics may actually decrease MACE.”

IBD patients receiving an oral small molecule did not have a significantly increased risk for coronary artery disease (aOR, 1.05; 95% CI, 0.82 – 1.33; P = .7148) or myocardial infarction (aOR, 1.04; 95% CI 0.60 – 1.78; P = .8903). The risk of stroke was lower but not significantly different (aOR, 0.87; 95% CI, 0.57 – 1.33; P = .5148).

In addition, there was no significant change in risk for venous thromboembolism (aOR 1.07; 95% CI, 0.83 – 1.39; P = .5957).

All cohorts were matched for age, race, sex, cardiovascular risk factors, and medications including immunomodulators, 5-aminosalicylic acids, and steroids. MACE and VTE were noted by ICD-10 codes at least 30 days after starting treatment.

Strengths of the study included large sample size, diverse cohorts, and propensity score matching. Limitations included the study’s retrospective design.

Difference in IBD and Rheumatoid Arthritis Populations

The authors noted: “Although further study is needed, it is possible that adequate treatment of bowel inflammation in IBD patients results in a decreased risk of MACE.”

Regueiro and colleagues are updating and expanding the research to increase the number of patients. They are also planning to evaluate the long-term extension data with individual biologics and small molecules to assess the consistency of their findings. “On preliminary glance, we believe that our results will be consistent with future study.”

“When you look at the studies, the increase in cardiac risk issues we’re seeing are in rheumatoid arthritis. And when we look at the patients with inflammatory bowel disease, we don’t see it,” session co-moderator John Leighton, MD, said when asked to comment. “So we think that there is a difference in the two populations, and this study gives further credence to that.”

“There are probably some high-risk populations that we still want to be careful with,” added Leighton, professor of medicine and chair of the Division of Gastroenterology at Mayo Clinic in Phoenix, Arizona. “But the risk is not as great as they initially saw in the rheumatoid [arthritis] patients — and it’s a good thing because these drugs work very well.”

American College of Gastroenterology (ACG) 2023 Annual Scientific Meeting: Abstract 9. Presented October 23, 2023.

The study was independently supported. Lead author Qapaja had no relevant financial relationships. Miguel Regueiro is an advisory committee or board member and consultant for Alfasigma, Allergan, Amgen, Eli Lilly, Miraca Labs, Prometheus, Salix, Seres, and Target RWE. He serves on these roles and receives unrestricted educational grants from AbbVie, Bristol-Myers Squibb, Celgene, Genentech, Gilead Sciences, Janssen, Pfizer Inc, Takeda, and UCB. He also receives royalties from Wolters Kluwer Health. Leighton is an advisory committee/board member for Braintree.

Damian McNamara is a staff journalist based in Miami. He covers a wide range of medical specialties, including infectious diseases, gastroenterology and critical care. Follow Damian on Twitter:  @MedReporter.

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