Mucosal Healing in Ulcerative Colitis Patients with Week 8 Response to Adalimumab: Subanalysis of ULTRA 2

Abstract

Purpose: To investigate mucosal healing in adult patients with moderately to severely active ulcerative colitis (UC) failing conventional therapy who responded to induction with the anti-tumor necrosis factor (TNF) agent adalimumab (ADA) in the 52-week (wk), double-blind, randomized, placebo-controlled ULTRA 2 trial.1 Methods: Patients were stratified by prior anti-TNF use and randomized 1:1 to receive induction dosing with ADA 160/80 mg or placebo (PBO) at wks 0/2, then ADA 40 mg every other week or PBO from wk 4. Concomitant medications were maintained at stable doses, except corticosteroids, which could be tapered beginning at wk 8. Response to ADA induction was assessed at wk 8 in ADA-treated patients by full Mayo score (FMS; response = Mayo score decrease of ≥3 points and ≥30% from baseline and decrease in rectal bleeding score [RBS] of ≥1 or absolute RBS of 0 or 1) and partial Mayo score (PMS, Mayo score without endoscopy subscore; response = PMS decrease ≥2 points and ≥30% from baseline, and RBS criteria as above). At wk 52, the proportion of patients with mucosal healing (defined as a Mayo endoscopy subscore of 0 or 1) was assessed for ADA-treated patients who responded at wk 8 by FMS or PMS, compared with all PBO-treated patients, using non-responder imputation to handle missing data or for patients who moved to open-label dosing at any time (including patients who escalated to weekly dosing) for inadequate response. Subgroup analyses by prior anti-TNF use were also performed. The treatment groups were compared overall (Cochran-Mantel-Haenszel) and by subgroups (chi-square). Results: At wk 8 of ULTRA 2, 50.4% (125/248) of ADA-treated patients responded per FMS, and 49.6% (123/248) responded per PMS. Significantly more patients treated with ADA vs PBO achieved mucosal healing at wk 52, for both FMS and PMS responders (Table). Similar treatment effects at wk 52 were observed for anti-TNF-naïve and anti-TNF-exposed patients.Table: [1523]Conclusion: In patients with moderately to severely active UC in ULTRA 2, clinically meaningful long-term mucosal healing efficacy with ADA was seen at wk 52 in pts with wk 8 full or partial Mayo score response.