Efficacy and Safety of Etrasimod in a Phase 2 Randomized Trial of Patients With Ulcerative Colitis
| Autor: | Laurent Peyrin-Biroulet, Scott D. Lee, Preston Klassen, Severine Vermeire, Bruce R. Yacyshyn, T Kühbacher, Michael Chiorean, Christopher H Cabell, Jinkun Zhang, Snehal Naik, Julián Panés, William J. Sandborn |
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| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine Indoles Acetates Severity of Illness Index Inflammatory bowel disease law.invention Placebos 0302 clinical medicine S1P Receptor Modulator Randomized controlled trial law Clinical endpoint Intestinal Mucosa Atrioventricular Block Gastroenterology Colonoscopy Induction Chemotherapy Middle Aged Ulcerative colitis Treatment Outcome Female 030211 gastroenterology & hepatology medicine.symptom Gastrointestinal Hemorrhage Immunomodulatory Therapy Adult medicine.medical_specialty Colon Placebo Proof of Concept Study Asymptomatic 03 medical and health sciences Double-Blind Method Internal medicine medicine Humans Ulcerative Colitis Adverse effect Sphingosine-1-Phosphate Receptors Dose-Response Relationship Drug Hepatology business.industry Inflammatory Bowel Disease Rectum medicine.disease Confidence interval 030104 developmental biology Asymptomatic Diseases Colitis Ulcerative business |
| Zdroj: | Gastroenterology. 158:550-561 |
| ISSN: | 0016-5085 |
| DOI: | 10.1053/j.gastro.2019.10.035 |
| Popis: | BACKGROUND & AIMS: Etrasimod (APD334) is an oral, selective sphingosine 1-phosphate receptor modulator in development for immune-mediated inflammatory disorders. We assessed the efficacy and safety of etrasimod in patients with moderately to severely active ulcerative colitis (UC). METHODS: In a phase 2, proof-of-concept, double-blind, parallel-group study, adult outpatients with modified Mayo Clinic scores (MCSs) (stool frequency, rectal bleeding, and endoscopy findings) of 4-9, endoscopic subscores of 2 or more, and rectal bleeding subscores of 1 or more were randomly assigned to groups given once-daily etrasimod 1 mg (n = 52), etrasimod 2 mg (n = 50), or placebo (n = 54) for 12 weeks. The study was performed from October 15, 2015, through February 14, 2018, at 87 centers in 17 countries. The primary endpoint was an increase in the mean improvement in modified MCS from baseline to week 12. Secondary endpoints included the proportion of patients with endoscopic improvement (subscores of 1 or less) from baseline to week 12. Exploratory endpoints, including clinical remission, are reported in the article, although the study was statistically powered to draw conclusions only on the primary endpoint. RESULTS: At week 12, the etrasimod 2 mg group met the primary and all secondary endpoints. Etrasimod 2 mg led to a significantly greater increase in mean improvement in modified MCS from baseline than placebo (difference from placebo, 0.99 points; 90% confidence interval, 0.30-1.68; P = .009), and etrasimod 1 mg led to an increase in mean improvement from baseline in modified MCS of 0.43 points more than placebo (90% confidence interval, reduction of 0.24 to increase of 1.11; nominal P = .15). Endoscopic improvement occurred in 41.8% of patients receiving etrasimod 2 mg vs 17.8% receiving placebo (P = .003). Most adverse events were mild to moderate. Three patients had a transient, asymptomatic, low-grade atrioventricular block that resolved spontaneously all patients had evidence of atrioventricular block before etrasimod exposure. CONCLUSIONS: In patients with moderately to severely active ulcerative colitis, etrasimod 2 mg was more effective than placebo in producing clinical and endoscopic improvements. Further clinical development is warranted. Clinicaltrials.gov, Number: NCT02447302. ispartof: GASTROENTEROLOGY vol:158 issue:3 pages:550-561 ispartof: location:United States status: published |
| Databáze: | OpenAIRE |
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