Golimumab: Response and Remission in 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-naïve 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.
Ulcerative colitis (UC) is a chronic inflammatory disease of the colon characterized by bloody diarrhea. Tumor necrosis factor (TNF) plays an important role in the pathogenesis of UC. Infliximab and adalimumab are monoclonal antibodies to TNF that have previously been shown to be effective for induction and maintenance therapy of moderately to severely active UC. However, there remains a need for additional treatment options.
Golimumab is a subcutaneously (SC) administered fully human anti-TNF antibody. Golimumab is approved for the treatment of rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis. The Program of Ulcerative Colitis Research Studies Utilizing an Investigational Treatment−Subcutaneous (PURSUIT-SC) study was an integrated phase 2 and phase 3 trial that evaluated the safety and efficacy of SC golimumab induction therapy in patients with moderate-to-severe UC.
Abstract and Introduction
Abstract
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-naïve 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.
Introduction
Ulcerative colitis (UC) is a chronic inflammatory disease of the colon characterized by bloody diarrhea. Tumor necrosis factor (TNF) plays an important role in the pathogenesis of UC. Infliximab and adalimumab are monoclonal antibodies to TNF that have previously been shown to be effective for induction and maintenance therapy of moderately to severely active UC. However, there remains a need for additional treatment options.
Golimumab is a subcutaneously (SC) administered fully human anti-TNF antibody. Golimumab is approved for the treatment of rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis. The Program of Ulcerative Colitis Research Studies Utilizing an Investigational Treatment−Subcutaneous (PURSUIT-SC) study was an integrated phase 2 and phase 3 trial that evaluated the safety and efficacy of SC golimumab induction therapy in patients with moderate-to-severe UC.
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