Etrasimod — an oral, selective sphingosine-1-phosphate receptor modulator — was effective in inducing endoscopic and histologic remission, as well as histological remission and mucosal healing in patients with moderately to severely active ulcerative colitis, according to study results presented at the Congress of the European Crohn’s and Colitis Organisation.
Laurent Peyrin-Biroulet, MD, PhD, of University Hospital of Nancy in France, said etrasimod (Arena Pharmaceuticals) uses a somewhat new mechanism of action.
“In multiple sclerosis there have been some pan-S1P modulators that have been developed,” he said during his presentation. “This is more specific with selectivity to S1P1, 4 and 5. So we expect better safety and efficacy.”
Researchers evaluated the drug in a randomized, placebo-controlled phase 2 study comprising 156 patients with UC. They randomly assigned patients to once-daily etrasimod 1 mg (n = 52) or 2 mg (n = 50) with no dose titration, or a placebo (n = 54). They assessed endoscopic severity at baseline and at week 12 by performing sigmoidoscopy with central reading using the Mayo endoscopic subscore. Researchers took biopsies, and a masked central pathologist scored histology results using the Geboes index.
Investigators used predefined endpoint definitions to assess endoscopic improvement (Mayo subscore of 0 or 1), histological improvement (Geboes score < 3.1), and histological remission (Geboes score < 2). They defined mucosal healing as both endoscopic improvement and histological remission.
Compared with placebo, more patients who received etrasimod 2 mg achieved endoscopic improvement (16.3% vs. 43.2%; P = .003), histological improvement (10.2% vs. 31.7%; P = .006), and histological remission (6.1% vs. 19.5%; P = .027). Researchers found that the etrasimod 1-mg dose also produced better outcomes, but the results did not reach statistical significance.
Peyrin-Biroulet said there was not a perfect agreement between endoscopic improvement and histological improvement for patients treated with etrasimod.
“We still need to work on it,” he said. “Mucosal healing seems to be achievable with this drug, and we will look at the upcoming phase 3 study.” – by Alex Young
Peyrin-Biroulet L, et al. Abstract OP09. Presented at: Congress of the European Crohn’s and Colitis Organisation; March 7-9, 2019; Copenhagen, Denmark.
Disclosure s : Peyrin-Biroulet reports he has financial ties to AbbVie, Alma, Amgen, Biogaran, Biogen, Boehringer Ingelheim, Celgene, Celltrion, Enterome, Ferring, Genentech, InDex Pharmaceuticals, Janssen, Lilly, Merck, Nestle, Pfizer, Pharmacosmos, Samsung Bioepis, Sandoz, Sterna, Takeda, Tillotts and Vifor. Please see the ECCO disclosure database for all other authors’ relevant financial disclosures.