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Research Article
24 February 2025

Matching-adjusted indirect comparisons of efficacy outcomes between etrasimod and ozanimod for moderately to severely active ulcerative colitis

Authors: Vipul Jairath https://orcid.org/0000-0002-1092-0033 [email protected], Tim Raine https://orcid.org/0000-0002-5855-9873, Thomas P Leahy https://orcid.org/0000-0003-3958-6224, Ravi Potluri https://orcid.org/0000-0002-0509-2659, Karolina Wosik https://orcid.org/0009-0002-7233-0933, David Gruben, Joseph C Cappelleri https://orcid.org/0000-0001-9586-0748, Peter Hur, and Lauren BartolomeAuthor Info & Affiliations
Volume 14, Number 4
https://doi.org/10.57264/cer-2024-0193
PDFFormats

Abstract

Aim: Etrasimod and ozanimod are selective sphingosine 1-phosphate receptor modulators targeting the S1P1,4,5, and S1P1,5 receptors, respectively, for the treatment of patients with moderately to severely active ulcerative colitis (UC). No head-to-head trial data exist between the two treatments. We compared these treatments indirectly using key efficacy outcomes from pivotal trials with induction and maintenance phase data adjusting for differences in clinical trial design and populations. Materials & methods: Individual patient data for etrasimod were matched to published aggregate data of ozanimod by key baseline characteristics. An anchored matching-adjusted indirect comparison (MAIC) was conducted for the induction period. An unanchored MAIC was utilized during the maintenance period due to differences in placebo arms between trials as a result of differing trial designs. Matching characteristics measured at baseline were age, sex, corticosteroid use, duration of UC, biologic exposure, modified Mayo score, and presence of left-sided colitis. Outcomes were clinical response and clinical remission for the induction period, and clinical response and clinical remission among induction phase responders for the maintenance period. Two sensitivity analyses were conducted. The first matched on prior TNFi exposure rather than biologic exposure, the second sensitivity analysis included an induction only etrasimod trial (ELEVATE UC 12). Results: There were no significant differences between etrasimod and ozanimod at the end of the induction period for clinical response and clinical remission, respectively (relative risk [RR] 0.98 [95% confidence interval (CI): 0.76–1.33], RR: 1.25 [95% CI: 0.71–2.92]). At the end of maintenance, etrasimod demonstrated improved outcomes compared with ozanimod for both clinical response (RR: 1.18 [95% CI: 1.05–1.30]) and clinical remission among induction phase responders (RR: 1.33 [95% CI: 1.12–1.55]). In the sensitivity analysis that matched on prior TNFi exposure rather than biologic exposure, there were no notable differences compared with the primary analyses. In the sensitivity analysis pooling ELEVATE UC 12 and ELEVATE UC 52 data, results were similar for clinical response (RR: 0.90 [95% CI: 0.75–1.10]) but etrasimod showed reduced efficacy for clinical remission (RR: 0.72 [95% CI: 0.50–1.12]) compared with the primary analysis, though overall remained not significantly different from ozanimod. Conclusion: MAIC results suggest that patients receiving etrasimod have similar induction results but are more likely to have clinical response and clinical remission at the end of the maintenance phase compared with patients receiving ozanimod. Despite the approach to ensure similarity between the trials by weighting, residual imbalance is possible, and results should be interpreted in the context of the assumptions.

Plain language summary: Comparing the effectiveness of etrasimod & ozanimod for treating moderate to severe ulcerative colitis

What is this article about?

This study compares two medications, etrasimod and ozanimod, used to treat moderate to severe ulcerative colitis. Since no trial exists comparing etrasimod and ozanimod directly, an analytical method called matching-adjusted indirect comparison was used to analyze and compare the effectiveness of these treatments. The study evaluated outcomes during both the induction phase and maintenance phase.

What were the results?

During the induction phase, there were no significant differences between etrasimod and ozanimod in achieving clinical response or clinical remission. However, during the maintenance phase, etrasimod-treated patients showed better results. Patients receiving etrasimod were more likely to achieve clinical response and clinical remission compared with those receiving ozanimod. Sensitivity analyses confirmed these findings, although results varied slightly when pooling additional etrasimod trial data in the induction period.

What do the results mean?

The results suggest that both etrasimod and ozanimod are effective for induction treatment, but etrasimod may offer better remission and response outcomes over the maintenance period. These findings could help physicians make informed decisions about treatment options for ulcerative colitis. However, results should be interpreted in the context of the assumptions of this study.

Supplementary Material

File (supplementary materials.docx)

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