A practical guide to selecting and using new ulcerative colitis therapies

Area of Science:

• Gastroenterology
• Immunology
• Pharmacology

Background:

• Several new biologics and small molecules, including mirizikizumab, upadacitinib, ozanimod, and etrasimod, are now approved for moderate-to-severe ulcerative colitis.
• Head-to-head clinical trials are lacking to guide the optimal positioning and use of these emerging advanced therapies.

Purpose of the Study:

• To review the efficacy and safety of new ulcerative colitis treatments.
• To propose a practical guide for positioning these novel agents in clinical practice.

Main Methods:

• Review of Phase III clinical trial data for new ulcerative colitis therapies.
• Indirect evidence synthesis using network meta-analysis.
• Expert opinion integration for treatment guidance.

Main Results:

• In biologic-experienced patients, ozanimod, etrasimod, and mirizikizumab showed lower induction clinical remission rates compared to upadacitinib.
• Network meta-analysis suggests upadacitinib may be more efficacious than other advanced therapies in both biologic-naive and experienced patients.
• Upadacitinib was associated with the highest risk of adverse events.

Conclusions:

• Novel agents like mirizikizumab, upadacitinib, ozanimod, and etrasimod expand therapeutic options for ulcerative colitis.
• For mild-to-moderate disease, ozanimod or etrasimod are suggested as first-line agents.
• For moderate-to-severe disease, mirizikizumab is favored as a first-line agent, while upadacitinib or mirizikizumab are considerations for anti-TNF-refractory patients, balancing efficacy and safety.