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Long-term Safety of Vedolizumab for the Treatment of Ulcerative Colitis or Crohnʼs Disease

2013; Lippincott Williams & Wilkins; Volume: 108; Linguagem: Inglês

10.14309/00000434-201310001-01674

1572-0241

Jean‐Frédéric Colombel, Bruce E. Sands, Stephen B. Hanauer, Paul Rutgeerts, William J. Sandborn, Silvio Danese, Geert R. DʼHaens, Remo Panaccione, Serap Sankoh, Irving H. Fox, Asit Parikh, Catherine Milch, Brian G. Feagan,

Immunodeficiency and Autoimmune Disorders

Purpose: Vedolizumab (VDZ) is an investigational, humanized monoclonal antibody targeting α4β7 integrin for treating ulcerative colitis (UC) or Crohn's disease (CD). Methods: An ongoing open-label extension study (NCT00790933) assesses VDZ safety in patients (pts) with moderately to severely active UC/CD, who were VDZ naive or had participated in either a phase 2 or 3 VDZ trial. Pts receive 300 mg VDZ intravenously every 4 weeks in the extension study. Adverse events (AEs) were summarized by descriptive statistics for interim data collected through July, 2012. Results: Mean (standard deviation) baseline ages were 41.3 (13.30) and 37.7 (12.52) years in UC and CD, respectively. Across VDZ studies, VDZ exposure was ≥6, ≥12, and ≥24 months for 1,534, 1,149, and 502 pts, respectively. AEs are summarized in the Table. Drug-related AEs were similar for UC and CD, most commonly including headache, 6%; nasopharyngitis, 4%; nausea, 4%; arthralgia, 4%; upper respiratory infection, 3%; and fatigue, 3%. Consistent with underlying disease, gastrointestinal disorders were the most frequently reported serious AEs, and included disease exacerbation in both UC patients (8%) and CD patients (11%). Infection and infestation AEs, of which upper respiratory infections (UC, 38%; CD, 34%) and abdominal and gastrointestinal infections (UC, 7%; CD, 12%) were most common, generally occurred at similar incidences in UC and CD patients. Except for anal abscess in CD (2%), all serious infection incidences were <1%, both overall and by indication. No cases of systemic candidiasis, disseminated herpes zoster, cytomegalovirus hepatitis or encephalitis, pneumocystis pneumonia, or progressive multifocal leukoencephalopathy were noted. AEs that most commonly led to discontinuation were gastrointestinal, with UC and CD exacerbations being most common (5% each). Malignancies were observed in <1% of pts (two colon cancers, two malignant melanomas).TableConclusion: Results support the long-term safety of VDZ treatment in UC and CD. The safety profile was consistent with that observed in previous 1-year, phase 3 randomized, placebo-controlled trials. This research was funded by Millennium Pharmaceuticals, Inc., a Takeda Company, Cambridge, MA. Disclosure - J.-F. Colombel - Financial support for research: Ferring, MSD, Abbott Laboratories, Lecture fee(s): Abbott Laboratories, Centocor, Ferring, Given Imaging, Shire, MSD, UCB Pharmaceuticals, Tillotts, Consultancy: Takeda Pharmaceuticals, Abbott Laboratories, Amgen, Biogen Idec Inc, Boehringer-Ingelheim, Bristol-Myers Squibb, Cellerix SL, ChemoCentryx Inc, Centocor, Cosmo Technologies, Elan Pharmaceuticals, Genentech, Giuliani, Given Imaging, GlaxoSmithKline, Hospira, Immune Pharmaceuticals, MSD, Neovacs, Ocera Therapeutics, Pfizer, Prometheus, Shire Pharmaceuticals, Synta Pharmaceuticals, Teva Pharmaceuticals, Therakos, UCB Pharmaceuticals, TXCell, Wyeth, Shareholder: Intestinal Biotech Development, Other: Takeda Pharmaceuticals, Schering-Plough, Abbott Laboratories, Centocor, MSD; B. Sands - Financial support for research: Takeda Pharmaceuticals, Abbott Immunology, Janssen Biotech, Celgene, Pfizer, UCB, GlaxoSmithKline, Prometheus Laboratories, Lecture fee(s): Mechanisms in Medicine, Creative Educational Concepts, Curatio CME, IMEDEX, Consultancy: Takeda Pharmaceuticals, Abbott Immunology, Amgen, Astellas Pharmaceutical Global Development, Avaxia Biologics, Axcan Pharmaceuticals, Biogen Idec, Bristol-Myers Squibb, Janssen Biotech, Chandler Chicco Agency, Cornerstones, Emmi Solutions, Elan Pharmaceuticals, Merrimack Pharmaceuticals, Pfizer, Prometheus Laboratories, Kyowa Hakko Kirin Pharma Inc, Vertex Pharmaceuticals, Strategic Consultants International, Dyax, GlaxoSmithKline, Puretech Ventures, Novartis, Baxter Healthcare Corporation, Dainippon Sumitomo Pharm Co, Immune Pharmaceuticals Corporation, Teva Pharmaceuticals, Shareholder: Avaxia Biologics; S. Hanauer - Financial support for research: Millennium Pharmaceuticals, Takeda Pharmaceuticals, Consultancy: Takeda Pharmaceuticals, Millennium Pharmaceuticals, Other: Takeda Pharmaceuticals, Millennium Pharmaceuticals; P. Rutgeerts - Financial support for research: Takeda Pharmaceuticals, Millennium Pharmaceuticals, Centocor (J&J), Merck, UCB, Abbott, Lecture fee(s): Centocor (J&J), Merck, UCB, Abbott, Genentech, Consultancy: Takeda Pharmaceuticals, Centocor (J&J), Merck, UCB, Abbott, Millennium, Genentech, Neovacs, Merck-Serono, BMS, Robarts, Tillotts, Pfizer, Falk Pharma; W. Sandborn - Financial support for research: Millennium Pharmaceuticals, Abbott Laboratories, Bristol-Myers Squibb, Genentech, GlaxoSmithKline, Janssen (previously Centocor), Novartis, Pfizer, Procter and Gamble Pharmaceuticals, Shire Pharmaceuticals, UCB Pharma, Lecture fee(s): Abbott Laboratories, Bristol-Myers Squibb, Janssen (previously Centocor), Consultancy: Takeda Pharmaceuticals, Millennium Pharmaceuticals, Abbott Laboratories, ActoGeniX NV, AGI Therapeutics Inc, Alba Therapeutics Corporation, Albireo, Alfa Wasserman, Amgen, AM-Pharma BV, Anaphore, Astellas Pharmaceuticals, Athersys Inc, Atlantic Healthcare Limited, Axcan Pharma (now Aptalis), BioBalance Corporation, Boehringer-Ingelheim Inc, Bristol-Myers Squibb, Celgene, Celek Pharmaceuticals, Cellerix SL, Cerimon Pharmaceuticals, ChemoCentryx, CoMentis, Cosmo Technologies, Coronado Biosciences, Cytokine Pharmasciences, Eagle Pharmaceuticals, Eisai Medical Research Inc, Elan Pharmaceuticals, EnGene Inc, Eli Lilly, Enteromedics, Exagen Diagnostics Inc, Ferring Pharmaceuticals, Flexion Therapeutics Inc, Funxional Therapeutics Limited, Genzyme Corporation, Genentech (now Roche), Gilead Sciences, Given Imaging, GlaxoSmithKline, Human Genome Sciences, Ironwood Pharmaceuticals (previously Microbia Inc), Janssen (previously Centocor), KaloBios Pharmaceuticals Inc, Lexicon Pharmaceuticals, Lycera Corporation, Meda Pharmaceuticals (previously Alaven Pharmaceuticals), Merck Research Laboratories, MerckSerono, Millennium Pharmaceuticals (subsequently merged with Takeda), Nisshin Kyorin Pharmaceuticals Co Ltd, Novo Nordisk A/S, NPS Pharmaceuticals, Optimer Pharmaceuticals, Orexigen Therapeutics Inc, PDL Biopharma, Pfizer, Procter and Gamble, Prometheus Laboratories, ProtAb Limited, Purgenesis Technologies Inc, Relypsa Inc, Salient Pharmaceuticals, Salix Pharmaceuticals Inc, Santarus, Schering Plough Corporation (acquired by Merck), Shire Pharmaceuticals, Sigmoid Pharma Limited, Sirtris Pharmaceuticals Inc (a GSK company), S.L.A. Pharma (UK) Limited, Targacept, Teva Pharmaceuticals, Therakos, Tillotts Pharma AG (acquired by Zeria Pharmaceutical Co Ltd), TxCell SA, UCB Pharma, Viamet Pharmaceuticals, Vascular Biogenics Limited (VBL), Warner Chilcott UK Limited, Wyeth (now Pfizer), Shareholder: Enteromedics, Other: Millennium Pharmaceuticals, Dickinson, Prud'Homme, Adams & Ingram, S. Danese - Lecture fee(s): Vifor Pharma, MSD, Consultancy: Ferring, Takeda Pharmaceuticals, Abbott, MSD, Vifor Pharma, Novo Nordisk, AstraZeneca, UCB, Pfizer, Other: MSD; G. D'Haens - Financial support for research: Abbott Laboratories, Janssen Biologics, Given Imaging, MSD, DrFalk Pharma, Photopill, Lecture fee(s): Abbott Laboratories, Tillotts, Tramedico, Ferring, MSD, UCB, Norgine, Shire and Vifor Pharma, Consultancy: Abbott Laboratories, Actogenix, Centocor, Cosmo, Engene, Ferring Pharmaceuticals, GlaxoSmithKline, Janssen Biologics, Millennium Pharmaceuticals, MSD, Novo Nordisk, PDL Biopharma, Pfizer, SetPoint, Shire, Takeda Pharmaceuticals, Teva Pharmaceuticals, UCB, Directorship(s): Robarts Clinical Trials, ON, Canada; R. Panaccione - Financial support for research: AbbVie, Janssen, GSK, Amgen, Prometheus, BMS, Pfizer, Chemocentryx, Takeda Pharmaceuticals, Lecture fee(s): AbbVie, Janssen, Ferring, Warner Chilcott, Takeda Pharmaceuticals, UCB, Merck, Shire, Consultancy: AbbVie, Janssen, Ferring, Warner Chilcott, Takeda Pharmaceuticals, UCB, Merck, Shire, Aptalis, Salix, Falk Pharma, Prometheus; S. Sankoh - Other: Employee of Millennium Pharmaceuticals; I. Fox - Shareholder: Millennium Pharmaceuticals, Other: Employee of Millennium Pharmaceuticals; A. Parikh - Shareholder: Takeda Pharmaceuticals, Other: Employee of Takeda Pharmaceuticals; C. Milch - Shareholder: Millennium Pharmaceuticals, Other: Employee of Millennium Pharmaceuticals; B. Feagan - Financial support for research: Takeda Pharmaceuticals, Lecture fee(s): Johnson and Johnson, Abbott Laboratories, UCB, Shire, Consultancy: Takeda Pharmaceuticals, Johnson and Johnson, Centocor, Elan/Biogen, Bristol-Myers Squibb, Celgene, CombinatoRx, UCB Pharma, Napo Pharma, Abbott Laboratories, Procter and Gamble, Berlex, Ore Pharmaceuticals, Cerimon Pharma, Genentech, Tillotts, Unity Pharmaceuticals, Albireo Pharma, Salix Pharma, Novo Nordisk, GSK, Astra Zeneca, Serono, Given Imaging Inc, Actogenix, Prometheus Therapeutics and Diagnostics, Athersys, Axcan, Gilead, Nektar, Pfizer, Shire, Wyeth, Zealand Pharma, Zyngenia, GICare Pharma, Sigmoid Pharma. This research was supported by an industry grant from Millennium Pharmaceuticals, Inc., a Takeda Company.