Gastroenterology

Gastroenterology

Volume 146, Issue 1, January 2014, Pages 96-109.e1
Gastroenterology

Original Research
Full Report: Clinical—Alimentary Tract
Subcutaneous Golimumab Maintains Clinical Response in Patients With Moderate-to-Severe Ulcerative Colitis

Presented in part at United European Gastroenterology Week (oral presentation, Amsterdam, The Netherlands), and at the annual meeting of The American College of Gastroenterology 2012 (oral presentation, Las Vegas, NV).
https://doi.org/10.1053/j.gastro.2013.06.010Get rights and content

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.

Section snippets

Patients

PURSUIT-M (NCT00488631) was a phase 3, multicenter, placebo-controlled, double-blind, randomized-withdrawal study conducted at 251 centers between September 2007 and October 2011. The institutional review board or ethics committee at each site approved the protocol, and patients provided written informed consent. All authors had access to the study data and reviewed and approved the final manuscript.

Participants in PURSUIT-M had completed 1 of 2 golimumab induction studies: PURSUIT-IV or

Patient Disposition, Baseline Characteristics, and Baseline Concomitant Medications

The PURSUIT-M study was conducted at 251 sites in Eastern Europe (477 patients), North America (323 patients), Asia Pacific and South Africa (237 patients), and Western Europe and Israel (191 patients). Overall, 1228 patients were enrolled from the induction studies, including 464 patients who were randomized in the primary analysis population (ie, were in clinical response to golimumab at week 6 of an induction study) and 764 patients who were enrolled but not randomized (ie, nonrandomized

Discussion

PURSUIT-M was a phase 3, placebo-controlled, randomized withdrawal study that evaluated the efficacy and safety of golimumab maintenance therapy. PURSUIT-M was a randomized withdrawal study of an anti-TNFα biologic agent in UC evaluating 2 golimumab maintenance doses. The target population for this study comprised patients with moderate-to-severe UC who were in clinical response to golimumab induction after participation in companion induction studies. The primary end point, maintenance of

Acknowledgments

Editorial and writing support were provided by James P Barrett, BS and Mary Whitman, PhD (Janssen Services, LLC). Members of the PURSUIT-Maintenance Study Group are listed in the Appendix.

This study was designed and conducted by the PURSUIT-Maintenance Steering Committee (WJS, BGF, J-FC, WR, PRG, JC, GJ, PR) and Janssen Research and Development, LLC (CM, HZ, JJ, OA, RS, CG), who jointly analyzed and interpreted the data, and contributed to the manuscript: William Sandborn prepared the first

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    Authors names in bold designate shared co-first authorship.

    This article has an accompanying continuing medical education activity on page e14. Learning Objective: Upon completion of this CME activity, successful learners will be able to formulate a treatment plan which employs anti-tumor necrosis factor therapy with golimumab in patients with moderate to severe ulcerative colitis.

    Conflicts of interest The authors disclose the following: William Sandborn has received consulting fees from Abbott, ActoGeniX NV, AGI Therapeutics, Inc, Alba Therapeutics Corp, Albireo, Alfa Wasserman, Amgen, AM-Pharma BV, Anaphore, Astellas, Athersys, Inc, Atlantic Healthcare, Ltd, Aptalis, BioBalance Corp, Boehringer-Ingelheim, Bristol-Myers Squibb, Celgene, Celek Pharmaceuticals, Cellerix SL, Cerimon Pharmaceuticals, ChemoCentryx, CoMentis, Cosmo Technologies, Coronado Biosciences, Cytokine Pharmasciences, Eagle Pharmaceuticals, EnGene, Inc, Eli Lilly, Enteromedics, Exagen Diagnostics, Inc, Ferring Pharmaceuticals, Flexio Therapeutics, Inc, Funxional Therapeutics, Ltd, Genzyme, Corp, Gilead Sciences, Given Imaging, GlaxoSmithKline, Human Genome Sciences, Ironwood Pharmaceuticals, Janssen Research and Development, LLC, KaloBios Pharmaceuticals, Lexicon Pharmaceuticals, Lycera Corp, Meda Pharmaceuticals, Merck Research Laboratories, Merck Serono, Millenium Pharmaceuticals, Nisshin Kyorin Pharmaceuticals, Novo Nordisk, NPS Pharmaceuticals, Optimer Pharmaceuticals, Orexigen Therapeutics, Inc, PDL Biopharma, Pfizer, Procter and Gamble, Prometheus Laboratories, ProtAb, Ltd, Purgenesis Technologies, Inc, Relypsa, Inc, Roche, Salient Pharmaceuticals, Salix Pharmaceuticals, Santarus, Schering Plough, Shire Pharmaceuticals, Sigmoid Pharma, Ltd, Sirtris Pharmaceuticals, SLA Pharma UK, Ltd, Targacept, Teva Pharmaceuticals, Therakos, Tilliotts Pharma AG, TxCell SA, UCB Pharma, Viamet Pharmaceuticals, Vascular Biogenics, Ltd, Warner Chilcott UK, Ltd, and Wyeth; has received research grants from Abbott, Bristol-Myers Squibb, Genentech, GlaxoSmithKline, Janssen Research and Development, LLC, Milennium Pharmaceuticals, Novartis, Pfizer, Procter and Gamble, Shire Pharmaceuticals, and UCB Pharma; has received payments for lectures/speakers bureau from Abbott, Bristol-Myers Squibb, and Janssen Research and Development, LLC; and holds stock/stock options in Enteromedics. Brian Feagan has received consulting fees from Millennium, Merck, Janssen Research and Development, LLC, Elan/Biogen, Janssen-Ortho, Teva Pharmaceuticals, Bristol-Myers Squibb, Celgene, UCB Pharma, Abbott, Astra Zeneca, Serono, Genentech, Tillotts, Unity Pharmaceuticals, Albireo Pharma, Given Imaging, Inc, Salix Pharm, Novonordisk, GlaxoSmithKline, Actogenix, Prometheus Therapeutics and Diagnostics, Athersys, Axcan, Gilead, Nektar, Pfizer, Shire, Wyeth, Zealand Pharm, Zyngenia, gICare Pharma, Inc, and Sigmoid Pharma; has received research grants from Merck, Millennium, Tillotts, Abbott, Protein Design Labs, Novartis, Janssen Research and Development, LLC, Elan/Biogen, UCB Pharma, Bristol-Myers Squibb, Genentech, CombinatoRx, ActoGeniX, and Wyeth; has received payments for lectures/speakers bureau from UCB, Abbott, Janssen Research and Development, LLC; and has served as a Scientific Advisory Board member for Astra Zeneca, Elan/Biogen, Merck, Celgene, Novartis, UCB Pharma, Salix Pharmaceuticals, Abbott Laboratories, Pfizer, Tillotts Pharma AG, and Prometheus Laboratories. Jean-Federic Colombel has served as a consultant, advisory board member, or speaker for Abbott Laboratories, Bristol Meyers Squibb, Ferring, Genentech, Giuliani SPA, Given Imaging, Janssen Research and Development, LLC, Merck & Co, Millenium Pharmaceuticals, Inc, Pfizer, Inc, Prometheus Laboratories, Sanofi, Schering Plough Corporation, Takeda, Teva Pharmaceuticals, and UCB Pharma (previously named Celltech Therapeutics, Ltd). Walter Reinisch has served as a speaker, consultant, and/or advisory board member for Abbott Laboratories, Aesca, Amgen, Astellas, Astra Zeneca, Biogen IDEC, Bristol-Myers Squibb, Cellerix, Chemocentryx, Celgene, Janssen Research and Development, LLC, Danone Austria, Elan, Ferring, Genentech, Grünenthal, Johnson & Johnson, Kyowa Hakko Kirin Pharma, Lipid Therapeutics, Millenium, Mitsubishi Tanabe Pharma Corporation, MSD, Novartis, Ocera, Otsuka, PDL, Pharmacosmos, Pfizer, Procter & Gamble, Prometheus, Robarts Clinical Trial, Schering-Plough, Setpointmedical, Shire, Takeda, Therakos, Tigenix, UCB Pharma, Vifor, Yakult Austria, and 4SC. Peter R Gibson has received consulting fees from Ferring Pharmaceuticals, Abbott, Janssen Research and Development, LLC, Schering-Plough, and Merck; he has received research support from Falk Pharma GmbH, Shire, Orphan Australia, Abbott Fresenius Kabi, and Norgine; and payment for lectures from Abbott, Merck, Janssen Research and Development, LLC, and Fresenius Kabi. Judith Collins has received research funding from Janssen Research and Development, LLC, and UCB Pharma; and has served on the speakers bureau for Salix. Gunnar Järnerot has received research funding from Janssen Research and Development, LLC. Paul Rutgeerts has received research funding and/or served as a speaker, consultant, and/or advisory board member for Abbott Laboratories, Janssen Research and Development, LLC, Merck Research Laboratories, Merck Serono, UCB Pharma, Millenium/Takeda, Genentech/Hoffman LaRoche, Neovacs, Bristol Myers Squibb, Robarts, Tillotts, Pfizer, and Falk Pharma. Colleen Marano, Richard Strauss, Hongyan Zhang, Jewel Johanns, Omoniyi Adedokun, and Cynthia Guzzo are employees of Janssen Research and Development, LLC.

    Funding The study was funded by Janssen Research & Development, LLC (Spring House, PA).

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