Long-Term Efficacy of Adalimumab for Treatment of Moderately to Severely Active Ulcerative Colitis

Abstract

To evaluate long-term efficacy of adalimumab (ADA) for patients with moderately to severely active ulcerative colitis (UC). The ADA UC development program consists of two trials (ULTRA 1 and ULTRA 2)1,2 followed by an ongoing multicenter open-label (OL) extension. Patients entering the extension on OL weekly ADA dosing continued on same. Patients entering the extension study from any blinded cohort (ADA or placebo [PBO]) or an OL cohort receiving ADA 40 mg every other week (eow) received OL ADA 40 mg eow. For patients entering from a blinded cohort, increase to 40 mg weekly for flare or non-response was allowed at or after week 12. For patients entering from an OL cohort, increase to 40 mg weekly for flare or non-response was allowed at or after week 12 for patients in clinical response at entry, or week 2 for patients with inadequate response at entry. Adjustments to concomitant medications including corticosteroids were allowed per protocol specifications. Partial Mayo score (PMS, Mayo score without endoscopy subscore) was collected at every study visit during the lead-in trials and the OL extension. Mean PMS over time through 2 years (112 weeks) from first dose of ADA was assessed using observed case method in the “any ADA” population (patients who received at least one dose of ADA in the lead-in or extension trials,) using a data cut off of 31 July 2011. The proportion of patients in clinical remission per PMS (PMS ≤2 with no subscore >1) at week 60 of the OL extension was assessed in the intent-to-treat (ITT) population (patients enrolled in the extension, excluding patients from sites non-compliant with good clinical practices), using the last observation carried forward (LOCF) method to handle missing data. The observed mean PMS at day of first dose of ADA was 5.9 (n = 992), and decreased over time through 112 weeks of treatment to 1.8 (N = 444, Table). Of the 588 ITT patients from the lead-in studies who enrolled into the OL extension, 351 (59.7%, LOCF) achieved clinical remission per PMS at week 60 of the OL extension. No new safety signals were observed. The results of the ongoing extension trial support clinically meaningful efficacy of adalimumab for the treatment of moderately to severely active UC, sustained for up to 2 years.