VANCOUVER, B.C.—New data on a recently approved therapy for ulcerative colitis suggest that its onset of action is uncommonly fast.
According to patient-maintained diaries, the selective sphingosine 1-phosphate (S1P) receptor modulator etrasimod (Velsipity, Pfizer) achieved faster reductions in symptoms and rates of remission relative to placebo.
The rapid treatment effect is relevant to selecting therapy and setting patient expectations, according to primary investigator Maria C. Dubinsky, MD, the co-director of the Susan and Leonard Feinstein Inflammatory Bowel Disease Clinical Center at Mount Sinai, in New York City.
The post hoc analysis of speed of response in patients treated with etrasimod was presented at the 2023 annual meeting of the American College of Gastroenterology (plenary 33), just two weeks after the drug received approval on the basis of two phase 3 clinical trials.
In the ELEVATE UC 52 and the ELEVATE UC 12 phase 3 trials, patients recorded daily symptoms with an electronic diary. They included overall improvement in symptoms as well as specific symptoms, such as rectal bleeding and stool frequency. The speed of benefit was evaluated in pooled patients from the two studies, 527 patients randomized to etrasimod 2 mg once daily and 260 placebo patients.
At baseline, patients were well matched, with a partial modified Mayo score (pMMS) of 4.0, Mayo rectal bleeding subscore (RBS) of 1.6 and Mayo stool frequency subscore (SFS) of 2.4.
Based on the e-diaries, graphs for symptomatic response—defined as at least a 30% change in baseline from the pMMS plus at least a 1-point improvement in both RBS and SFS—separated almost immediately. By day 2, the difference in the proportion of patients with a symptomatic response in the two groups was significant (5.56%; 95% CI, 0.79%-10.33%; P=0.02).
The graphs for symptomatic remission—defined as RBS score of 0 and SFS score of 0 with at least a 1-point improvement from baseline, separated more slowly—but the difference was significant by day 11 (4.69%; 95% CI, 0.36%-9.03%; P=0.034). From the point that the difference in symptoms became statistically significant, the curves for both symptomatic response and symptomatic remission continued to separate for the remainder of follow-up.
When stool frequency and rectal bleeding were evaluated separately, there also was a rapid separation of curves in favor of etrasimod. For the outcome of stool frequency normalization, this was achieved in three days (P=0.009). For rectal bleeding, this was achieved in 15 days (P=0.045). Again, there was further separation of the curves with extended follow-up.
Continued Positive Results
Full results of the ELEVATE UC 12 and ELEVATE UC 52 studies were published in the Lancet early in 2023 (2023;401[10383]:1159-1171). Both trials produced positive results for both primary and secondary end points. In the ELEVATE UC 52 study, for example, the rate of clinical remission was more than four times higher in participants treated with etrasimod than in those given placebo (32% vs. 7%; P<0.0001). Etrasimod was also safe and well tolerated, with a similar proportion of etrasimod and placebo patients experiencing serious adverse events in both trials.
In another subanalysis of the two ELEVATE trials presented at ACG (abstract P2200), corticosteroid treatment in combination with etrasimod was evaluated. There was a significant benefit for the etrasimod group whether patients were or were not using corticosteroids at baseline.
“Across both ELEVATE trials, there were fewer serious adverse events and serious infections in the etrasimod patients not taking [corticosteroids] at baseline,” reported Bruce E. Sands, MD, MS, the chief of the Division of Gastroenterology at Mount Sinai, in New York City, who presented the data. But, he added, “regardless of concomitant [corticosteroid] use at baseline, etrasimod demonstrated benefits at weeks 12 and 52.”
Although treatment effectiveness was greater in patients not taking corticosteroids, the likelihood of a complete remission relative to placebo was significant for etrasimod patients whether they were taking corticosteroids or not (both, P<0.001), Dr. Sands reported.
The speed of response observed in the ELEVATE trials, if true, is potentially important, according to Russell D. Cohen, MD, the director of the Inflammatory Bowel Disease Center at the University of Chicago. “I agree that the rapid time to improvement in stool frequency and rectal bleeding beginning as early as day 2 is quite impressive as well as encouraging as we introduce etrasimod to our patients with moderate to severely active UC. Hopefully, real-world clinical experience will replicate this important finding.”
—Ted Bosworth
Dr. Cohen reported financial relationships with AbbVie, Boehringer Ingelheim, Celgene, Genentech, Gilead, Medimmune, Pfizer, Schwarz and Takeda. Dr. Dubinsky reported financial relationships with more than 10 pharmaceutical companies, including Pfizer, which provided funding for this study and produces etrasimod. Dr. Sands reported financial relationships with more than 50 pharmaceutical companies including Pfizer.
This article is from the January 2024 print issue.