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 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. ClinicalTrials.gov numbers NCT02447302, NCT02536404.

Small Molecule Drugs in Inflammatory Bowel Diseases

“…At week 12, the clinical improvement (a change from the baseline in the three-component Mayo Clinic Score) was higher in patients treated with 2 mg of etrasimod compared with the placebo (difference, 0.99 points; 90% CI 0.30–1.68) as well as the endoscopic improvement (41.8% vs. 17.8% for the placebo; p = 0.003). In the open-label extension study including 118 patients receiving 2 mg of etrasimod daily up to week 52, 64% of patients had a clinical response, 33% had clinical remission, and 43% had an endoscopic improvement [ 102 ]. Patients who achieved a clinical response, clinical remission, or an endoscopic improvement at week 12 maintained the effect of the treatment with 85%, 60%, and 69% of patients with a clinical response, clinical remission, or an endoscopic improvement, respectively, at the end of treatment.…”

“…A total of 60% of the patients experienced treatment emergent adverse events (TEAEs), the most common being worsening of UC (19%) and anemia (11%). When excluding patients with worsening of UC, 51% of the patients (46/91) experienced a TEAE and three patients experienced a serious adverse event [ 102 ].…”

Selective Forms of Therapy in the Treatment of Inflammatory Bowel Diseases

“…A total of 22% of patients maintained steroid-free clinical remission. Thus, long-term use of etrasimod at a dose of 2 mg per day was safe and brought measurable benefits to the patients [28].…”

“…The study showed that in patients with moderate to severe UC, 2 mg of etrasimod led to significant clinical and endoscopic improvement. Following completion of the OASIS study, patients had the option of continuing etrasimod 2 mg treatment for an additional 34-40 weeks as part of an open-label extension (OLE protocol) [28]. The study was conducted in 14 countries and 51 clinical sites.…”

Review article: the sphingosine 1 phosphate/sphingosine 1 phosphate receptor axis ‐ a unique therapeutic target in inflammatory bowel disease

“…Current safety data show a favourable safety profile but are limited by a relatively small number of participants. 81 Currently, there are several ongoing phase III studies in severely active ulcerative colitis (NCT04706793, NCT03950232, NCT03996369, NCT04176588, and NCT03945188) and moderate-to-severe Crohn's disease (NCT04173273).…”