Crohn’s Disease Therapies: Similar Safety Profiles Across Treatments

The safety profiles of commonly used advanced therapies for Crohn’s disease appear broadly similar, offering reassurance to both patients and clinicians as treatment decisions are made. A recent study, published March 23, 2026, indicates comparable risks of serious infections, major adverse cardiovascular events, and venous thromboembolism across several advanced Crohn’s disease treatments. This suggests that selecting a therapy can be guided more by a drug’s effectiveness and individual patient factors than by broad safety concerns.

Understanding the Landscape of Crohn’s Disease Treatment

Crohn’s disease, a chronic inflammatory bowel disease, has seen a surge in treatment options over the past decade with the development of both biologic and small molecule therapies. These advancements have significantly improved outcomes for many individuals, but also introduced questions about long-term safety. While clinical trials provide initial safety data, they often involve highly selected patient populations and relatively short follow-up periods. This new research aims to address the gap in understanding real-world safety profiles.

“Much of the existing safety data arrive from clinical trials, which often have relatively short follow-up and highly selected patient populations,” explained Siddharth Singh, MD, professor of medicine at Mayo Clinic College of Medicine, in an interview with Healio. “Patients and clinicians frequently question whether certain newer therapies carry higher risks of serious infections, blood clots or cardiovascular events compared to older biologics.”

The Comparative Effectiveness Research Study

Researchers, led by Dr. Singh, conducted a comparative effectiveness study using data from the OptumLabs Data Warehouse, a large database of deidentified medical and pharmacy claims. The study compared the risks associated with several advanced therapies used to treat Crohn’s disease between January 2016 and December 2022. The analysis included over 12,245 adult patients with Crohn’s disease, with an average follow-up period of nearly 27 months.

The therapies examined included tumor necrosis factor-alpha antagonists (TNF antagonists), vedolizumab (Entyvio), ustekinumab (Stelara), risankizumab (Skyrizi), and upadacitinib (Rinvoq). These represent a range of drug classes with different mechanisms of action, making a direct comparison of their safety profiles particularly valuable.

Key Findings: Similar Safety Profiles

The study found that the incidence rate of serious infections varied somewhat across therapies, with the lowest rates observed for interleukin-12/23p40 antagonists and the highest for interleukin-23p19 antagonists. However, after adjusting for potential confounding factors, the researchers found no statistically significant differences in the risk of serious infections between the different drug classes when compared to TNF antagonists. This included anti-integrins, IL-12/23p40 antagonists, IL-23p19 antagonists, and Janus kinase (JAK) inhibitors.

Similarly, no significant differences were observed in the incidence of venous thromboembolism (VTE) or major adverse cardiovascular events (MACE) across the therapies. Rates for VTE ranged from 0.9 to 2.33 per 100 person-years, while rates for MACE ranged from 0.68 to 1.49 per 100 person-years – remaining consistently low across all treatment groups. These findings align with growing evidence suggesting that the overall risk of blood clots in IBD patients is complex and influenced by multiple factors beyond medication choice.

Implications for Treatment Decisions

These findings challenge the perception that newer therapies, such as vedolizumab and risankizumab, are inherently safer than older biologics or JAK inhibitors. Dr. Singh emphasized that the study suggests treatment decisions should prioritize a drug’s effectiveness, patient preferences, prior treatment history, and coexisting medical conditions, rather than assuming substantial safety differences between drug classes.

“This [research] suggests that treatment decisions can be guided primarily by effectiveness, patient preferences, prior treatment history and comorbidities, rather than assuming large safety differences between drug classes,” Dr. Singh stated.

Contextualizing the Risks: Absolute vs. Relative

It’s important to note that while the study found no significant differences between therapies, the absolute event rates for serious infections, VTE, and MACE were generally low across all groups. This suggests that, while risks exist with any medication, they are relatively uncommon in the studied population. Understanding absolute risk – the actual chance of an event occurring – is crucial for informed decision-making, as opposed to focusing solely on relative risk, which compares risks between groups.

Looking Ahead: Further Research and Personalized Medicine

While this study provides valuable insights, Dr. Singh acknowledges the need for further investigation. Longer-term data and more granular analyses are needed to understand safety profiles in specific high-risk subgroups, such as older adults and patients with cardiovascular risk factors. As treatment guidelines continue to evolve with the introduction of new therapies, ongoing research is essential to refine our understanding of the benefit-risk balance for each medication.

Future studies should also incorporate disease severity metrics and patient-reported outcomes to provide a more comprehensive assessment of treatment effects. The ultimate goal is to move towards more personalized treatment selection, balancing effectiveness and safety for each individual patient. The researchers also suggest that head-to-head comparative effectiveness studies that integrate both safety and effectiveness outcomes will be especially important.

Siddharth Singh, MD, can be reached at [email protected].

Source: Park S, et al. JAMA Netw Open. 2026;doi:10.1001/jamanetworkopen.2025.57922.