Etrasimod Elicits Rapid Symptom Improvement for Ulcerative Colitis

Marla C. Dubinsky, MD

Mount Sinai Kravis Children’s Hospital

Treatment with the S1P_1,4,5 receptor modulator etrasimod (Velsipity) elicited rapid symptomatic improvements, with significance differences compared with placebo seen as early as 2 days post-treatment initiation in patients with ulcerative colitis (UC), according to data from daily e-diaries submitted in the ELEVATE UC 52 and ELEVATE UC 12 studies that were presented at the American College of Gastroenterology (ACG) 2023 Annual Scientific Meeting in Vancouver, Canada.¹

Across patients treated in the study, rapid symptomatic response more common in those treated with etrasimod, which was seen early and reached significance at 2 days post-treatment initiation (5.56% difference at day 2 between groups; 95% CI, 0.79-10.33; P = .022). A statistically significant difference in symptomatic remission was achieved at day 11 (difference between groups, 4.69%; 95% CI, 0.35-9.03; P = .034). The difference between groups continued to increase throughout the course of the study.

"There were clinically relevant symptomatic improvements in patients treated with etrasimod vs placebo as early as day 2, particularly as it relates to stool frequency," lead investigator Marla C. Dubinsky, MD, Mount Sinai Kravis Children’s Hospital, said during a presentation of the results. "These findings suggest etrasimod has a rapid treatment effect with early symptomatic response. It is important for us to be aware of how quickly these drugs work when we're making treatment decision for our patients."

In the ELEVATE UC 52 trial, 433 patients with UC were enrolled to either a 12-week induction of once daily 2-mg etrasimod or matched placebo. After induction, these treatment arms continued 40 weeks of maintenance therapy. In the ELEVATE UC 12 trial, 354 patients were enrolled to a 12-week induction period of 2-mg daily etrasimod or placebo. Across studies, 260 patients received placebo and 527 were treated with etrasimod.

Baseline characteristics between groups were evenly matched, specifically for the baseline readings for rectal bleeding sub (RBS), stool frequency subscore (SFS), and partial modified Mayo score (pMMS). The mean for those in both groups was 1.6 for RBS, 2.4 for SFS, and 4.0 for pMMS. Rectal bleeding remission was defined as RBS of 0 and stool frequency normalization was defined as SFS of 0. Data for the analysis came from patient e-diaries, which allowed for additional insight into the symptomatic experience of patients, said Dubinsky.

A significant difference in remission of rectal bleeding was seen at day 15 between the etrasimod group and the placebo arm. The difference between arms at this point was 6.33% (95% CI, 0.14-12.51; P = .045). The first significant difference in stool frequency normalization was seen at day 3. At this point, the difference between the groups was 3.51% for SF normalization (95% CI, 0.87-6.14; P = .009). The differences between groups increased with additional treatment and remained consistent throughout the study.

"These data will help us frame expectations with our patients, when we're deciding what we're going to do with them and how quickly they can expect to be better," said Dubinsky. "This sets some realistic expecting for both us and our patients."

Full findings from the 2 studies indicated a higher rate of clinical remission and clinical response with etrasimod compared with placebo during the 12-week induction periods.² The clinical remission rates were 27% with etrasimod compared with 7% for placebo in the ELEVATE UC 52 study and 26% and 15%, respectively, in the ELEVATE UC 12 study. Based on the findings from the ELEVATE UC 52 and 12 studies, the FDA approved etrasimod for the treatment of patients with moderately to severely active UC on October 13, 2023.

In the ELEVATE UC 52 trial, adverse event (AEs) were reported in 71% of patients treated with etrasimod compared with 56% of those in the placebo arm. In the ELEVATE UC 12 trial, AEs were reported in 47% of patients treated with etrasimod compared with 47% in the placebo arm.

References

1. ^{Dubinsky MC, Vermeire S, Chaparro M, et al. 33 - Symptomatic Improvement Observed Within 2 Days of Etrasimod Induction Therapy: Results from ELEVATE UC 52 and ELEVATE UC 12 Studies in Patients with Ulcerative Colitis. Presented at: ACG 2023 Annual Meeting; October 20-25, 2023. Abstract 33.}
2. ^{Sandborn WJ, Vermeire S, Peyrin-Biroulet L, et al. Etrasimod as induction and maintenance therapy for ulcerative colitis (ELEVATE): two randomised, double-blind, placebo-controlled, phase 3 studies. Lancet. 2023;401(10383):1159-1171. doi: 10.1016/S0140-6736(23)00061-2}