Vedolizumab, Adalimumab, and Methotrexate Combination Therapy in Crohn’s Disease (EXPLORER)

• DOI: 10.1016/j.cgh.2023.09.010
• Publication Date: 2023-09-22T16:50:15Z
• Authors: Jean-Frederic Col...; Ryan C. Ungaro; Bruce E. Sands; Corey A. Siegel; Douglas C. Wolf; John F. Valentine; Brian G. Feagan; Blue Neustifter; Harisha Kadali; Pradeep Nazarey; Alexandra James; Vipul Jairath; Rana M. Qasim Khan
• Keywords: Vedolizumab; Clinical endpoint; Combination therapy

BACKGROUND & AIMS Although biologics have revolutionized treatment of Crohn's disease (CD), an efficacy ceiling has been reached. Combining biologic therapies may improve remission rates. METHODS EXPLORER, a phase 4, single-arm, open-label study, evaluated triple combination therapy with vedolizumab (300 mg on day 1, weeks 2 and 6, then every 8 weeks), adalimumab (160 2, 80 at week 40 methotrexate (15 weekly) in biologic-naïve patients newly diagnosed, moderate- to high-risk CD. Endoscopic 26 (primary end point; Simple Score for Disease [SES-CD] ≤2), clinical 10 (secondary Activity Index [CDAI] <150), incidences adverse events serious (SAEs) were evaluated. RESULTS Among 55 enrolled patients, mean CD duration was 0.4 years, baseline SES-CD 12.6, CDAI 265.5. At 26, 19 (34.5%) endoscopic remission. 34 (61.8%) 30 (54.5%), respectively, Post hoc Bayesian analysis demonstrated that the probabilities produced higher rate (33.5%; 95% credible interval, 22.4–45.7) than placebo (14%), monotherapy (27%), or (30%) ≥99.9%, 86.3%, 71.4%, respectively. Six had SAEs. CONCLUSIONS Combination resulted 34.5% 54.5% no safety signal related regimen. This supports further evaluation ClinicalTrials.gov number: NCT02764762.