Gastroenterology

Gastroenterology

Volume 146, Issue 1, January 2014, Pages 85-95
Gastroenterology

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

https://doi.org/10.1053/j.gastro.2013.05.048Get rights and content

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.

Section snippets

Patients

The PURSUIT-SC induction study (NCT00487539) was a multicenter, randomized, double-blind, placebo-controlled trial conducted between July 2007 and November 2010. The Institutional Review Board or ethics committee at each study site approved the protocol, and all patients provided written informed consent. All authors had access to the study data and had reviewed and approved the final manuscript.

Eligible patients had an established diagnosis of UC and moderate-to-severe disease activity,

Patient Disposition, Baseline Characteristics, and Baseline Concomitant Medications

The PURSUIT-SC study was conducted at 217 sites in Eastern Europe (400 patients), North America (278 patients), Asia Pacific and South Africa (204 patients), and Western Europe and Israel (183 patients). Discontinuation rates were low during all study phases (Figure 1AC). Overall, 1030 (96.7%) of 1065 randomized patients completed study participation through week 6 (Figure 1D).

The randomized study population comprised 56% men, with a median age of 38.0 years. Patients had UC for a median of

Discussion

The PURSUIT-SC induction study employed an adaptive seamless phase 2/3 clinical trial design, an alternative concept to the traditional drug development programs of sequential, independent clinical trials. The confirmatory, seamless phase 2/3 clinical trial has developed as a means of efficiently combining the “learning” (phase 2) and “confirmatory” (phase 3) stages of drug development.22

The objective of the phase 2 portion of the study was to identify optimal golimumab induction regimens for

Acknowledgments

The authors thank Michelle Perate, MS, Mary Whitman, PhD, and James P. Barrett, BS (Janssen Services, LLC) for providing writing support.

Members of the PURSUIT-SC study group are listed in the Supplementary Material.

References (23)

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    Author 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.

    Some of the data displayed in this article were presented at Digestive Disease Week (oral presentation, San Diego, CA) May 19-22, 2012; United European Gastroenterology Week (oral presentation, Amsterdam, The Netherlands) October 20-24, 2012; and at the annual meeting of The American College of Gastroenterology (oral presentation, Las Vegas, NV) October 19-24, 2012.

    Conflicts of interest The authors disclose the following: William J. 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 & 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; research grants from Abbott, Bristol-Myers Squibb, Genentech, GlaxoSmithKline, Janssen Research & Development, LLC, Milennium Pharmaceuticals, Novartis, Pfizer, Procter and Gamble, Shire Pharmaceuticals and UCB Pharma; payments for lectures/speakers bureau from Abbott, Bristol-Myers Squibb and Janssen Research & Development, LLC; and holds stock/stock options in Enteromedics. Brian G. Feagan has received consulting fees from Millennium, Merck, Janssen Research & 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 Pharmaceuticals, Wyeth, Zealand Pharm, Zyngenia, gICare Pharma Inc., and Sigmoid Pharma; research grants from Merck, Milllennium, Tillotts, Abbott, Protein Design Labs, Novartis, Janssen Research & Development, LLC, Elan/Biogen, UCB Pharma, Bristol-Myers Squibb, Genentech, CombinatoRx, ActoGeniX, and Wyeth; payments for lectures/speakers bureau from UCB, Abbott, Janssen Research & Development, LLC; and served as 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-Frederic Colombel has served as consultant, advisory board member or speaker for Abbott, Bristol Meyers Squibb, Ferring, Genentech, Giuliani SPA, Given Imaging, Janssen Research & Development, LLC, Merck & Co., Millenium Pharmaceuticals Inc., Pfizer. Prometheus Laboatories, Sanofi, Schering Plough Corporation, Takeda, Teva Pharmaceuticals, UCB Pharma (previously named Celltech Therapeutics, Ltd). Walter Reinisch has served as a speaker, consultant and/or advisory board member for Abbott, Aesca, Amgen, Astellas, Astra Zeneca, Biogen IDEC, Bristol-Myers Squibb, Cellerix, Chemocentryx, Celgene, Janssen Research & 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, Abbott, Janssen Research & Development, LLC, Schering-Plough and Merck; research support from Falk Pharma GmbH, Shire, Orphan Australia, Abbott Fresenius Kabi and Norgine; and payment for lectures from Abbott, Merck, Janssen Research & Development, LLC and Fresenius Kabi. Judith Collins has received research funding from Janssen Research & Development, LLC., UCB Pharma and has served on the speakers bureau for Salix. Gunner Järnerot has received research funding from Janssen Research & Development, LLC. Toshifumi Hibi has received consulting fees from Janssen Research & Development, LLC. Paul Rutgeerts has received research funding, and/or served as speaker, consultant and/or advisory board member for Abbott, Janssen Research & 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, Hongyan Zhang, Richard Strauss, Jewel Johanns, Omoniyi J. Adedokun, and Cynthia Guzzo are employees of Janssen Research & Development, LLC.

    Funding The study was funded by Janssen Research & Development, LLC (Spring House, PA). This study was designed and conducted by the PURSUIT-SC Steering Committee (WJS, BGF, J-FC, WR, PRG, JC, GJ, TH, and PR) and Janssen Research & Development, LLC (CM, HZ, RS, JJ, OJA, and CG) who jointly analyzed and interpreted the data and contributed to the manuscript: WJS prepared the first draft of the manuscript and the PURSUIT-SC Steering Committee made the decision to publish. The corresponding author had full access to all of the data and takes full responsibility for the veracity of the data and data analysis.

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