Subcutaneous Golimumab Induces Clinical Response and Remission in Patients With Moderate-To-Severe Ulcerative Colitis

Gastroenterology. 2014 Jan;146(1):85-95; quiz e14-5. doi: 10.1053/j.gastro.2013.05.048. Epub 2013 Jun 2.

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.

Keywords: AZA; C-reactive protein; CRP; Dose−Response; Human Monoclonal Antibody; IBDQ; Inflammatory Bowel Disease; Inflammatory Bowel Disease Questionnaire; PK; PURSUIT-SC; Program of Ulcerative Colitis Research Studies Utilizing an Investigational Treatment−Subcutaneous; SC; TNF; TNF Antagonist; UC; azathioprine; pharmacokinetic; subcutaneous; tumor necrosis factor; ulcerative colitis.

Publication types

  • Clinical Trial, Phase II
  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Cortex Hormones / therapeutic use
  • Adult
  • Aminosalicylic Acids / therapeutic use
  • Anti-Inflammatory Agents / therapeutic use*
  • Antibodies, Monoclonal / therapeutic use*
  • Azathioprine / therapeutic use
  • Colitis, Ulcerative / drug therapy*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Injections, Subcutaneous
  • Male
  • Mercaptopurine / therapeutic use
  • Methotrexate / therapeutic use
  • Middle Aged
  • Quality of Life
  • Remission Induction / methods
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*

Substances

  • Adrenal Cortex Hormones
  • Aminosalicylic Acids
  • Anti-Inflammatory Agents
  • Antibodies, Monoclonal
  • Immunosuppressive Agents
  • Tumor Necrosis Factor-alpha
  • golimumab
  • Mercaptopurine
  • Azathioprine
  • Methotrexate

Associated data

  • ClinicalTrials.gov/NCT00487539