Long-term Safety and Efficacy of Etrasimod for Ulcerative Colitis: Results from the Open-label Extension of the OASIS Study

Abstract

Background and aims: Etrasimod is an oral, selective, sphingosine 1-phosphate receptor modulator. In a phase 2, randomised, double-blind, placebo-controlled trial in adults with moderately-to-severely active ulcerative colitis [OASIS], etrasimod 2 mg provided significant benefit versus placebo and was generally well tolerated. This open-label extension [OLE] evaluated safety and efficacy of etrasimod for up to 52 weeks.

Methods: In OASIS, 156 patients received etrasimod 1 mg, etrasimod 2 mg, or placebo, once daily for 12 weeks. After completing OASIS, patients could enrol in the OLE and receive etrasimod 2 mg for an additional 34-40 weeks.

Results: In all, 118 patients enrolled in the OLE; 112 patients received etrasimod 2 mg at any point and were evaluated for safety and efficacy. A total of 92 [82%] patients who received etrasimod 2 mg in the OLE completed the study. Treatment-emergent adverse events occurred in 60% [67/112] of patients receiving etrasimod 2 mg at any time, most commonly worsening ulcerative colitis and anaemia; 94% of adverse events were mild/moderate. At end of treatment, 64% of patients met the criteria for clinical response, 33% for clinical remission, and 43% for endoscopic improvement. Week 12 clinical response, clinical remission, or endoscopic improvement was maintained to end of treatment in 85%, 60%, or 69% of patients, respectively. Steroid-free clinical remission occurred in 22% of overall patients.

Conclusions: In this long-term extension study, etrasimod 2 mg demonstrated a favourable safety profile. Most patients with clinical response, clinical remission, or endoscopic improvement at Week 12 maintained that status to end of treatment.

Keywords: Ulcerative colitis; etrasimod; long-term extension study.

Figure 1.

Study design.

Figure 2.

Patient disposition. DB, double-blind; ITT, intention-to-treat; OLE, open-label extension.

Figure 3.

Change from DB baseline in lymphocyte count by treatment in the DB study [evaluable cohort]. All patients received etrasimod 2 mg during the OLE. During the DB study, 1 mg and 2 mg groups were treated with etrasimod 1 mg and 2 mg, respectively. The evaluable cohort included patients who received any etrasimod 2 mg during the OLE and had the same treatment assignment throughout the OLE. In this ‘as observed’ analysis, only patients with non-missing assessments were included, and no missing data were imputed. DB, double-blind; EOT, end of treatment; OLE, open-label extension; PBO, placebo; SE, standard error.

Figure 4.

Proportion of patients with sustained response from Week 12 to EOT [ITT population]. All patients received etrasimod 2 mg during the OLE. The overall group includes patients who received any treatment [placebo, etrasimod 1 mg, or etrasimod 2 mg] during the DB study. The etrasimod 2 mg treat-through group received etrasimod 2 mg during both the DB study and OLE. In these NRI analyses, data missing for any reason were imputed as non-response. CI, confidence interval; DB, double-blind; EOT, end of treatment; ITT, intention-to-treat; n, number of patients; NRI, non-responder imputation; OLE, open-label extension; Wk, week.