PHILADELPHIA – Use of etrasimod was associated with improved clinical and endoscopic results, and was generally safe and well tolerated compared with placebo in patients with moderate to severe ulcerative colitis, according to a recent award-winning presentation at the annual meeting of the American College of Gastroenterology.
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Dr. William J. Sandborn
“Patients with moderate to severe ulcerative colitis receiving etrasimod 2 mg per day achieved statistically significant and clinically meaningful differences in all of the primary and secondary endpoints, and most exploratory endpoints were also significantly proved,” William J. Sandborn, MD, AGAF, FACG, professor of clinical medicine at the University of California, San Diego, stated in his presentation at the meeting. “A dose-response relationship was observed in virtually all of the measures of treatment efficacy.”
The abstract received the ACG Auxiliary Award (Member), which is given to ACG members each year with outstanding abstract submissions.
Dr. Sandborn and his colleagues enrolled 156 patients with ulcerative colitis (UC) into the OASIS study, a randomized, double-blind, parallel-group, phase 2 study of etrasimod, an oral sphingosine 1-phosphate (S1P) receptor modulator, compared with placebo. Patients were aged 18-80 years, with moderate to severe UC as defined by a three-component Mayo Clinic Score (MCS) comprising rectal bleeding, frequency of stool, and endoscopy.
Those patients who achieved an MCS score between 4 and 9 points with an endoscopic subscore of at least 2 and rectal bleeding (RB) subscore of at least 1 were included. Patients were divided into once-daily etrasimod 1 mg (52 patients), once-daily etrasimod 2 mg (50 patients) and placebo (54 patients) groups and treated over a 12-week period.
At 12 weeks, the least-squares mean difference for change in baseline in three-component MCS was 1.94 in the 1-mg etrasimod group and 2.49 in the 2-mg etrasimod group compared with placebo (1.50). Endoscopic improvement was greater in the 1-mg etrasimod (22.5%) and 2-mg (41.8%) groups compared with placebo (17.8%); endoscopic remission rates also improved in the 1-mg etrasimod (13.7%) and 2-mg (15.3%) groups compared with placebo (5.3%). Lymphocyte count circulation significantly decreased in the 1-mg etrasimod (37.2%) and 2-mg (57.3%) groups compared with the placebo group. With regard to rectal bleeding, the rectal bleeding subscore also decreased in the 1-mg etrasimod and 2-mg groups compared with placebo at 12 weeks from baseline.
The researchers noted no significant differences in adverse events among groups, with the placebo group showing a higher rate of major adverse events (11.1%) compared with the 1-mg etrasimod (5.8%) and 2-mg etrasimod (0%) groups.
“The OASIS trial results for etrasimod would support proceeding to a phase 3 program for this drug in patients with moderate to severe ulcerative colitis,” Dr. Sandborn concluded.
Dr. Sandborn reports consultancies, speaker bureau memberships, and research support from AbbVie, Biogen, Celgene, Ferring, Genentech, Gilead Sciences, Immune Pharmaceuticals, Janssen, Lilly, MedImmune, Novartis, Pfizer, Regeneron, Ritter Pharmaceuticals, Salix, Theradiag, UCB Pharma, and Vascular Biogenics, among others.
SOURCE: Sandborn WJ et al. ACG 2018. Presentation 11.