Subcutaneous Golimumab Maintains Clinical Response in Patients With Moderate-To-Severe Ulcerative Colitis

Gastroenterology. 2014 Jan;146(1):96-109.e1. doi: 10.1053/j.gastro.2013.06.010. Epub 2013 Jun 14.

Abstract

Background & aims: Subcutaneous golimumab, a fully human monoclonal antibody to tumor necrosis factor-α (TNFα), was evaluated as maintenance therapy in TNFα antagonist-naive adults with moderate-to-severe active ulcerative colitis, despite conventional therapy, who responded to golimumab induction therapy.

Methods: We performed a phase 3, double-blind trial of patients who completed golimumab induction trials (Program of Ulcerative Colitis Research Studies Utilizing an Investigational Treatment, eg, PURSUIT). Patients who responded to induction therapy with golimumab (n = 464) were assigned randomly to groups given placebo or injections of 50 or 100 mg golimumab every 4 weeks through week 52. Patients who responded to placebo in the induction study continued to receive placebo. Nonresponders in the induction study received 100 mg golimumab. The primary end point was clinical response maintained through week 54; secondary end points included clinical remission and mucosal healing at both weeks 30 and 54.

Results: Clinical response was maintained through week 54 in 47.0% of patients receiving 50 mg golimumab, 49.7% of patients receiving 100 mg golimumab, and 31.2% of patients receiving placebo (P = .010 and P < .001, respectively). At weeks 30 and 54, a higher percentage of patients who received 100 mg golimumab were in clinical remission and had mucosal healing (27.8% and 42.4%) than patients given placebo (15.6% and 26.6%; P = .004 and P = .002, respectively) or 50 mg golimumab (23.2% and 41.7%, respectively). Percentages of serious adverse events were 7.7%, 8.4%, and 14.3% among patients given placebo, 50 mg, or 100 mg golimumab, respectively; percentages of serious infections were 1.9%, 3.2%, and 3.2%, respectively. Among all patients given golimumab in the study, 3 died (from sepsis, tuberculosis, and cardiac failure, all in patients who received 100 mg golimumab) and 4 developed active tuberculosis.

Conclusions: Golimumab (50 mg or 100 mg) maintained clinical response through week 54 in patients who responded to induction therapy with golimumab and had moderate-to-severe active ulcerative colitis; patients who received 100 mg golimumab had clinical remission and mucosal healing at weeks 30 and 54. Safety was consistent with that reported for other TNFα antagonists and golimumab in other approved indications. ClinicalTrials.gov number: NCT00488631.

Keywords: Fully Human Monoclonal Antibody; IV; Inflammatory Bowel Disease; NNT; PURSUIT; PURSUIT-M; Program of Ulcerative Colitis Research Studies Utilizing an Investigational Treatment; Program of Ulcerative Colitis Research Studies Utilizing an Investigational Treatment Maintenance; Randomized Withdrawal Trial; SC; TNFα; UC; intravenous; number needed to treat; subcutaneous; tumor necrosis factor-α; ulcerative colitis.

Publication types

  • 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*
  • Colitis, Ulcerative / drug therapy*
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Injections, Subcutaneous
  • Maintenance Chemotherapy / methods
  • Male
  • Mercaptopurine / therapeutic use
  • Methotrexate / therapeutic use
  • Middle Aged
  • Severity of Illness Index
  • 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
  • Methotrexate

Associated data

  • ClinicalTrials.gov/NCT00488631