Randomised clinical trial: a placebo-controlled study of intravenous golimumab induction therapy for ulcerative colitis.

ABSTRACT

BACKGROUND: Tumour necrosis factor alpha (TNFα)-antagonism effectively treats ulcerative colitis (UC). The golimumab clinical programme evaluated subcutaneous (SC) and intravenous (IV) induction, and SC maintenance regimens, in TNFα-antagonist-naïve patients with moderate-to-severe active UC despite conventional treatment. AIM: To evaluate dose-response relationship, select IV golimumab induction doses for continued development, and evaluate the safety and efficacy of selected doses. METHODS: Adults with Mayo scores of 6-12 and endoscopic subscores ≥2 were enrolled into this multicentre, randomised, double-blind, placebo-controlled, integrated Phase 2/3 dose-finding/dose-confirming study. In Phase 2, 176 patients were randomised (1111) to a single IV infusion of placebo, 1-, 2- or 4-mg/kg golimumab. While Phase 2 data were analysed to select doses for continued development, 71 additional patients were randomised. Phase 3 enrolment stopped after 44 additional patients were randomised (111) to placebo, 2- or 4-mg/kg golimumab. Due to insufficient power for the Phase 3 primary endpoint analysis (clinical response at week 6), efficacy analyses are considered exploratory and include all randomised patients. RESULTS: No dose-response was observed in Phase 2; however, higher serum golimumab exposure was associated with greater proportions of patients achieving more favourable clinical outcomes, clinical response and greater improvement in Mayo scores compared with placebo-treated patients and those with lower serum concentrations. Among all randomised patients, numerically greater proportions were in clinical response at week 6 in the 2- and 4-mg/kg golimumab groups compared with placebo [44.0% (33/75) and 41.6% (32/77) vs. 30.1% (22/73)]. CONCLUSIONS: Efficacy with single-dose golimumab IV induction was lower than expected and less than observed in the SC induction study. No new safety findings were observed. ClinicalTrials.gov Number, NCT00488774.