LAUSR

BACKGROUND & AIMS SERENE UC evaluated the efficacy of higher adalimumab induction and maintenance dose regimens in patients with ulcerative colitis (UC). METHODS This phase 3, double-blind, randomized trial included induction and maintenance studies, with a main study (ex-Japan) and Japan substudy. Eligible patients (18-75 years, full Mayo score [FMS] 6-12, centrally read endoscopy subscore 2-3) were randomized 3:2 to higher induction regimen (HIR; adalimumab 160mg at weeks 0, 1, 2, and 3) or standard induction regimen (SIR; 160mg at week 0, 80mg at week 2); all received 40mg at weeks 4 and 6. At week 8, all patients were rerandomized 2:2:1 (main study) to 40mg every week (ew), 40mg every other week (eow), or exploratory therapeutic drug monitoring; or 1:1 (Japan substudy) to 40mg ew or 40mg eow maintenance regimens. RESULTS In the main study, 13.3% vs 10.9% of patients receiving HIR vs SIR achieved clinical remission (FMS ≤2 with no subscore >1) at week 8 (induction primary endpoint; P=.265); among week-8 responders, 39.5% vs 29.0% receiving 40mg ew vs 40mg eow achieved clinical remission at week 52 (maintenance primary endpoint; P=.069). In the integrated (main+Japan) population, 41.1% vs 30.1% of week-8 responders receiving 40mg ew vs 40mg eow achieved clinical remission at week 52 (nominal P=.045). Safety profiles were comparable between dosing regimens. CONCLUSION Though primary endpoints were not met, a >10% absolute difference in clinical remission was demonstrated with higher adalimumab maintenance dosing. Higher dosing regimens were generally well tolerated and consistent with the known safety profile of adalimumab in UC. ClinicalTrials.gov number, NCT002209456.