Michael Chiorean, MD1, Séverine Vermeire, MD, PhD2, Julian Panés, MD3, Laurent Peyrin-Biroulet, MD, PhD4, Jinkun Zhang, PhD5, Bruce E. Sands, MD, FACG6, Krisztina Lazin, MD, MSc7, Chris H. Cabell, MD, MHS5, Snehal U. Naik, PhD5, Preston Klassen, MD5, William J. Sandborn, MD, FACG8
1Virginia Mason Medical Center, Seattle, WA; 2University Hospitals, Leuven, Vlaams-Brabant, Belgium; 3Hospital Clinic de Barcelona, IDIBAPS, CIBERehd, Barcelona, Catalonia, Spain; 4Lorraine University, Vandoeuvre-lès-Nancy, Lorraine, France; 5Arena Pharmaceuticals, San Diego, CA; 6Icahn School of Medicine at Mount Sinai, New York, NY; 7Arena Pharmaceuticals, Zug, Zug, Switzerland; 8University of California San Diego, La Jolla, CA
Introduction: Etrasimod, a once-daily, oral, selective, sphingosine-1-phosphate receptor modulator, was previously tested in the 12-week (wk) phase 2, randomized, placebo-controlled, double-blind (DB) OASIS study (NCT02447302) in adults with moderate–to–severe ulcerative colitis (UC). This open-label extension (OLE) study (NCT02536404) evaluated safety/efficacy of etrasimod for an additional 34 wk in OASIS completers.
Methods: All patients completing the DB study could enroll in the OLE and receive etrasimod 2 mg QD for a subsequent 34 wk. Efficacy was summarized in the modified intent-to-treat (mITT) population evaluable cohort, which included patients with required assessments who received etrasimod 2 mg throughout the OLE. The treat-through (TT) group received etrasimod 2 mg in both the DB and OLE studies. Endpoints were clinical remission (endoscopic score ≤1 [with absence of friability], rectal bleeding [RB] =0, and stool frequency [SF] score ≤1 with ≥1 point decrease from DB baseline), clinical response (clinical remission or decrease in modified Mayo Clinic score [endoscopy findings, RB, or SF] of ≥2 points and ≥30% decrease from DB baseline, with either a RB decrease of ≥1 or RB score of ≤1), and endoscopic improvement (subscore ≤1). All statistics are descriptive. End of treatment (EOT) was the last observation for each patient.
Results: 118 patients (84% of DB completers) entered the OLE; 112 patients received etrasimod 2 mg at any point in the OLE (safety population), of whom 105 received etrasimod 2 mg throughout the OLE (evaluable cohort), and 92 completed the OLE. At EOT, 70% of patients had a clinical response, increased from 40% at wk 12 (Table 1). Most patients with clinical response, clinical remission, or endoscopic improvement at wk 12 maintained that status at EOT (Table 2). Median lymphocyte reduction from DB baseline was 44.6% at wk 12 with etrasimod 2 mg and 42.9% at EOT in the TT group. In the safety population, 60% experienced ≥1 TEAE (mostly mild or moderate) and 9% stopped study drug due to a TEAE. Of 14 serious TEAEs in 7 patients, only 1 was considered treatment-related (worsening UC). Effects on heart rate and atrioventricular (AV) conduction were minimal; no patients withdrew due to bradycardia or AV block.
Discussion: Etrasimod 2 mg showed sustained clinical response, clinical remission, and endoscopic improvement at the end of the OLE. Etrasimod had a favourable long-term safety profile, with most AEs of mild to moderate severity; no new safety findings were reported.
Citation: Michael Chiorean, MD; Séverine Vermeire, MD, PhD; Julian Panés, MD; Laurent Peyrin-Biroulet, MD, PhD; Jinkun Zhang, PhD; Bruce E. Sands, MD, FACG; Krisztina Lazin, MD, MSc; Chris H. Cabell, MD, MHS; Snehal U. Naik, PhD; Preston Klassen, MD; William J. Sandborn, MD, FACG. P1409 - LONG-TERM EFFICACY AND SAFETY OF ETRASIMOD FOR ULCERATIVE COLITIS: RESULTS FROM THE OPEN-LABEL EXTENSION OF THE OASIS STUDY. Program No. P1409. ACG 2019 Annual Scientific Meeting Abstracts. San Antonio, Texas: American College of Gastroenterology.