William J Sandborn1, Brian G Feagan2, Colleen Marano3, Hongyan Zhang3, Richard Strauss3, Jewel Johanns3, Omoniyi J Adedokun3, Cynthia Guzzo4, Jean-Frederic Colombel5, Walter Reinisch6, Peter R Gibson7, Judith Collins8, Gunnar Järnerot9, Paul Rutgeerts10. 1. Division of Gastroenterology, University of California San Diego, La Jolla, California. Electronic address: wsandborn@ucsd.edu. 2. Robarts Research Institute, University of Western Ontario, London, Ontario, Canada. 3. Janssen Research and Development, LLC, Spring House, Pennsylvania. 4. Janssen Services, LLC, Horsham, Pennsylvania. 5. Department of Hepatogastroenterology and Centre d'Investigation Clinique Centre Hospitalier Universitaire de Lille, Université Lille Nord de France, Lille, France; Icahn School of Medicine at Mount Sinai, New York, New York. 6. Department of Gastroenterology and Hepatology, Universitätsklinik für Innere Medizin III, Vienna, Austria. 7. Department of Gastroenterology, Monash University, Alfred Hospital, Melbourne, Victoria, Australia. 8. Division of Gastroenterology, Department of Medicine, Oregon Health Sciences University, Portland, Oregon. 9. Division of Gastroenterology, Department of Medicine, Örebro University Hospital, Örebro, Sweden. 10. Department of Gastroenterology, University Hospital, Gasthuisberg, Leuven, Belgium.
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.
RCT Entities:
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