Etrasimod shows advantage over placebo in UC

In 2 phase 3 studies that comprised 2 outcomes of clinical remission for induction at week 12 and 1 endpoint at week 52, etrasimod demonstrated a significant benefit for patients with ulcerative colitis (UC). Key secondary endpoints were also met.

The selective sphingosine-1-phosphate (S1P) receptor modulator etrasimod was assessed for its potential benefits in treating adult patients with UC in the phase 3 ELEVATE UC 52 (NCT03945188) and ELEVATE UC 12 (NCT03996369) trials [1]. ELEVATE UC 52 had a so-called ‘treat-through’ design: the included 433 patients were randomised 2:1 to 2 mg of etrasimod or placebo and the co-primary endpoint was clinical remission at week 12 and week 52; patients who did not improve within the induction period were allowed to switch and be enrolled in the open-label extension study ELEVATE UC OLE (NCT03950232) at week 12. In ELEVATE UC 12, 354 adult patients were treated with 2 mg of etrasimod orally or placebo and the study was completed after 12 weeks with the primary endpoint being clinical remission, defined via the modified Mayo score (stool frequency subscore 0/1, rectal bleeding 0, endoscopic subscore of 0/1).

All participants were 16–80 years old, had moderate-to-severe UC, and a history of inadequate or loss of response to at least 1 treatment for UC, but not more than 2 biologics or 1 biologic and 1 JAK inhibitor. The demographics were well balanced across the different arms. On average, the disease duration was 7 years, about one-third of patients had extensive colitis, and the median Mayo score was 7. Between 51.7% and 61.1% of participants had a baseline endoscopic score of 3. Looking at prior treatment, 60% of participants were naïve and 40% were exposed; one-third was on concomitant steroids.

Clinical remission rates in ELEVATE UC 52 were statistically significant both at week 12 and week 52: 27% for etrasimod versus 7.4% for placebo and 32.1% for etrasimod versus 6.7% for placebo, respectively (P<0.001 for both comparisons). Also, key secondary endpoints like endoscopic improvement, symptomatic remission, and steroid-free remission were all positive. “There was not a single endpoint that was not met,” Prof. Séverine Vermeire (University Hospital Leuven, Belgium) summarised. In ELEVATE UC 12, both primary and secondary endpoints showed significant superiority of etrasimod over placebo.

“What I would like to highlight is that the treatment-emergent adverse events were overall balanced across the different groups,” Prof. Vermeire commented on the safety results, underlining that there was no signal in terms of serious or opportunistic infections whatsoever. She valued the safety profile consistent with previous trials.

“In both studies, treatment with etrasimod 2 mg daily resulted in clinically meaningful and statistically significant improvements in all pre-defined outcomes at week 12 and week 52,” Prof. Vermeire concluded.

1. Sandborn WJ, et al. Etrasimod 2mg once daily as treatment for moderately to severely active ulcerative colitis: results from the phase 3 ELEVATE UC 52 and ELEVATE UC 12 trials. OP086, UEG Week 2022, 8–11 October, Vienna, Austria.

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Posted on 1 December, 20228 April, 2024