TOPLINE

Compared with placebo, etrasimod demonstrated greater efficacy as a first-line advanced therapy in patients with ulcerative colitis (UC) who escalated treatment following failure of 5-aminosalicylates (5-ASA) alone. The treatment also seemed effective in patients previously exposed to other conventional therapies such as corticosteroids and thiopurines.

METHODOLOGY

• Researchers conducted a prespecified and post hoc subgroup analysis of two phase 3, placebo-controlled clinical trials to evaluate the efficacy of etrasimod 2 mg once daily vs placebo in patients with moderately to severely active UC.
• Trials included patients aged 16-80 years who had moderately to severely active UC defined by a modified Mayo score of 4-9.
• A total of 74 patients (45 receiving etrasimod, 29 receiving placebo) from one trial comprised the prespecified post-5-ASA failure subgroup, defined as patients with inadequate response, loss of response, or intolerance to 5-ASA without failure of other UC medications.
• Post hoc analyses assessed efficacy in pooled data from both trials: 197 patients in the post-5-ASA/corticosteroid subgroup (previously exposed to 5-ASA regardless of corticosteroid use, but naive to thiopurines and biologics/JAK inhibitors) and 104 patients in the post-thiopurine/5-ASA/corticosteroid subgroup (previously exposed to thiopurines regardless of 5-ASA or corticosteroid use, but naive to biologics/JAK inhibitors).
• Efficacy endpoints included clinical remission (stool frequency subscore, 0 or 1 with ≥ 1-point reduction from baseline, rectal bleeding subscore, 0, and endoscopic subscore [ES] ≤ 1), endoscopic improvement (ES ≤ 1), and other prespecified measures assessed at weeks 12 and 52.

TAKEAWAY

• In the post-5-ASA failure subgroup, significantly more patients receiving etrasimod vs placebo achieved clinical remission and endoscopic improvement at week 12 and week 52 (P < .001 for all).
• In the post-5-ASA/corticosteroid subgroup, clinical remission rates and endoscopic improvement were greater with etrasimod vs placebo at week 12 and week 52 (P < .001 for all).
• Among patients in the post-thiopurine/5-ASA/corticosteroid subgroup, clinical remission and endoscopic improvement were greater with etrasimod vs placebo at only week 12 (P < .001 and P = .011, respectively).
• No new safety events were observed.

IN PRACTICE

"Etrasimod thus provides an early advanced treatment option for advanced therapy candidates following conventional therapy failure. Expanded adoption of etrasimod use in this patient population is an opportunity to induce endoscopic and histologic remission in those earlier in their treatment journey," the authors wrote.

SOURCE

The study was led by David T. Rubin, University of Chicago Medicine Inflammatory Bowel Disease Center, Chicago. It was published online on July 27 in Therapeutic Advances in Gastroenterology.

LIMITATIONS

Many subgroup analyses included limited patient numbers. Some analyses were exploratory and post hoc, subject to false-positive results, potential confounding, and selection bias. Trial design excluded topical rectal therapies, which are commonly used in clinical practice before advanced therapy escalation. 

DISCLOSURES

Pfizer Inc. funded the study. Several authors are employees and shareholders of Pfizer or its affiliates. Some authors reported grant support, consulting relationships, consultancy and speaker, financial support, lecture fees, and other ties with multiple pharmaceutical companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.