Subcutaneous golimumab induces clinical response and remission in patients with moderate-to-severe ulcerative colitis
Background & Aims Little is known about the efficacy of golimumab, a fully human monoclonal antibody to tumor necrosis factor (TNF) −α, for treatment of ulcerative colitis (UC). We evaluated subcutaneous golimumab induction therapy in TNF−α antagonist-naive patients with moderate-to-severe UC despite conventional treatment. Methods We integrated double-blind phase 2 dose-finding and phase 3 dose-confirmation trials in a study of 1064 adults with UC (Mayo score: 6−12; endoscopic subscore ≥2; 774 patients in phase 3). Patients were randomly assigned to groups given golimumab doses of 100 mg and then 50 mg (phase 2 only), 200 mg and then 100 mg, or 400 mg and then 200 mg, 2 weeks apart. The phase 3 primary end point was week-6 clinical response. Secondary end points included week-6 clinical remission, mucosal healing, and Inflammatory Bowel Disease Questionnaire (IBDQ) score change. Results In phase 2, median changes from baseline in the Mayo score were −1.0, −3.0, −2.0, and −3.0, in the groups given placebo, 100 mg/50 mg, 200/100 mg, and 400/200 mg golimumab, respectively. In phase 3, rates of clinical response at week 6 were 51.0% and 54.9% among patients given 200 mg/100 mg and 400 mg/200 mg golimumab, respectively, vs 30.3% among those given placebo (both, P ≤ .0001). Rates of clinical remission and mucosal healing and mean changes in IBDQ scores were significantly greater in both golimumab groups vs the placebo group ( P ≤ .0014, all comparisons). Rates of serious adverse events were 6.1% and 3.0%, and rates of serious infection were 1.8% and 0.5%, in the placebo and golimumab groups, respectively. One patient in the 400 mg/200 mg group died as a result of surgical complications of an ischiorectal abscess. Conclusions Treatment with subcutaneous golimumab induces clinical response, remission, and mucosal healing, and increases quality of life in larger percentages of patients with active UC than placebo. ClinicalTrials.gov Number: NCT00487539.