Etrasimod Significantly Benefits Ulcerative Colitis Regardless of Corticosteroids

Etrasimod provided efficacy to patients with moderately to severely active ulcerative colitis (UC) regardless of their concomitant corticosteroid treatment status at both 12 and 52 weeks, according to new data.¹

In an abstract presented at the American College of Gastroenterology (ACG) 2023 Annual Scientific Meeting in Vancouver, BC this week, investigators led by Bruce E. Sands, MD, MS, of the Icahn School of Medicine at Mount Sinai, reported that concomitant steroid use was not influential to the treatment benefit of etrasimod in patients with UC treated in the ELEVATE UC 52 and ELEVATE UC 12 clinical trials. In fact, Sands and colleagues reported in their phase 3 subgroup analysis that patients without a history of concomitant steroid use at baseline reported greater treatment effect with etrasimod.

An oral, once-daily, selective sphingosine 1-phosphate (S1P) 1, 4, 5 receptor modulator, etrasimod was approved for the treatment of UC on the basis of the ELEVATE UC trial findings earlier this month.²

In the ELEVATE UC 52 and ELEVATE UC 12 trials, patients with moderately to severely active ulcerative colitis were randomized 2:1 to either once-daily etrasimod 2 mg or placebo. ELEVATE UC 12 included a 12-week induction period for patients, while ELEVATE UC 52 used a treat-through design with a 12-week induction period, followed by a 40-week maintenance period.

Patients on a stable dose for ≥4 weeks prior to screening endoscopy were permitted to receive oral contaminant corticosteroids for their condition at baseline: options of prednisone ≤20 mg daily, budesonide ≤9 mg daily, or equivalent treatment. However, investigators recommended corticosteroid tapering from week 12.

Sands and colleagues sought efficacy and safety outcomes with etrasimod in patients with and without concomitant corticosteroid use at baseline.

“This analysis really concerns what are the outcomes in patients who are on corticosteroids at baseline—whether they are any different from the patients who are not on corticosteroids,” Sands told HCPLive at ACG 2023. “Previously, other analyses have show that the drug is effective in achieving corticosteroid-free clinical remission at week 52.”

Approximately two-thirds (n = 93 [32.2%]) of patients receiving etrasimod in ELEVATE UC 52 were receiving corticosteroids at baseline, versus 29.2% (n = 42) patients receiving placebo. In ELEVATE UC, the disparity was 27.3% (n = 65) versus 29.3% (n = 34), respectively.

In ELEVATE UC 52, investigators observed that a greater proportion of etrasimod-treated patients receiving corticosteroids achieved the primary endpoint of clinical remission versus the placebo arm receiving corticosteroids at both week 12 (P <.05) and week 52 (P <.001). Additionally, the same outcome was observed among both treatment arms that which did not receive corticosteroids (P <.001).

In ELEVATE UC 12, a greater proportion of patients receiving etrasimod plus corticosteroids achieved complete remission at week 12 compared to patients receiving placebo plus corticosteroids (P >.05). Investigators observed a statistically significantly greater difference in this outcome among patients receiving etrasimod without corticosteroids compared to patients receiving placebo without corticosteroids (P <.01).

“Generally, what we find is, there’s not a tremendous amount of difference in terms of the outcomes, whether patients were on corticosteroids at baseline or not,” Sands said. “What is different, however, is you do see higher placebo response rates…suggesting that patients on steroids are effective being treated to some degree by their corticosteroids. It doesn’t increase the efficacy of etrasimod, and it doesn’t diminish the efficacy of etrasimod.”

Regarding safety, investigators observed fewer serious adverse events and infections among patients receiving etrasimod plus corticosteroids, than in those without corticosteroids. Among patients receiving placebo, corticosteroids were actually associated with a greater rate of serious adverse events.

“You wouldn’t intentionally start steroids, because there’s no additive benefit here,” Sands said. “But lots of patients are treated with steroids for flares, and you want to get them off the steroids. So we know that this drug can be effective in getting people off steroids.”

References

1. ^{Sands BE, Gecse KB, Rubin DT, Leung Y, et al. P2200 - Efficacy and Safety of Etrasimod in Patients With and Without Concomitant Corticosteroid Treatment in the Phase 3 ELEVATE UC 52 and ELEVATE UC 12 Trials. Paper presented at: ACG 2023 Annual Scientific Meeting. Vancouver, BC, Canada. October 20 – 25, 2023.}
2. ^{Brooks A. FDA Approves Etrasimod for Moderately to Severely Active Ulcerative Colitis. HCPLive. Published October 13, 2023. https://www.hcplive.com/view/fda-approves-etrasimod-for-moderately-to-severely-active-ulcerative-colitis}