Original ResearchFull Report: Clinical—Alimentary TractLong-term Efficacy and Safety of Stem Cell Therapy (Cx601) for Complex Perianal Fistulas in Patients With Crohn’s Disease
Graphical abstract
Section snippets
Study Design and Participants
This is a phase 3, randomized, double-blind, parallel-group, placebo-controlled study (NCT01541579) conducted in 49 hospitals in 7 European countries and Israel from July 6, 2012, to December 13, 2015 (ie, to the end of the 52-week follow-up). The study protocol was approved by the local ethics committee of participating centers and was conducted in accordance with the 2008 Declaration of Helsinki, as well as all relevant international, national, and local rules and regulations. Here, we report
Patients
In total, 212 patients were randomized to Cx601 (n = 107) or control (n = 105) (Supplementary Figure 1). The baseline demographic and clinical characteristics of patients in the Cx601 and control groups were similar, as previously described.17 In the mITT population (n = 204), the mean age of the patients was 38.3 years, 53.9% were male and 92.2% were white. Patients had Crohn’s disease for a mean of 11.6 years and more than 70% of patients had received antibiotics, immunosuppressants, or
Discussion
Complex perianal fistulas are debilitating for patients and challenging for physicians to treat. The ultimate goal of therapy is to provide long-term fistula healing. Using a robust efficacy endpoint combining remission evaluated both clinically and radiologically with MRI, the results of the current study demonstrate that the efficacy of Cx601 observed at 24 weeks was maintained for up to 1 year after administration in patients with Crohn’s disease with treatment-refractory complex perianal
Acknowledgments
ADMIRE CD Study Steering Committee Members:
Julián Panés, Daniel C. Baumgart, Jean F. Colombel, Silvio Danese, Gert Van Assche, and Walter Reinisch.
Global Surgical Coordinator: Damián García-Olmo.
In addition to the authors, the ADMIRE CD Study Group Collaborators include the following [to be mentioned as “Collaborators” in PubMed]:
Austria – Anton Stift (Medical University of Vienna); Jörg Tschmelitsch, Karl Mrak (St. Veit/Glan Hospital); Herbert Tilg, Irmgard Kroberger (University Clinic
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Conflicts of interest The authors disclose the following: Julián Panés has received personal fees from TiGenix, AbbVie, Boehringer Ingelheim, Celgene, Galapagos, Genentech-Roche, GSK, Janssen, MSD, Novartis, Oppilan, Pfizer, Takeda, Theravance, and Vivelix. Damián García-Olmo has received personal fees from TiGenix, and has a patent and a patent pending. Gert Van Assche has received personal fees from TiGenix and grants and personal fees from AbbVie, Takeda, MSD, Janssen, Pfizer, Ferring, and Genentech-Roche. Jean Frederic Colombel reports grants from AbbVie, Janssen and Janssen, and Takeda; other fees from Boehringer Ingelheim, Celgene Corporation, Celtrion, Enterome, Ferring, Genentech, Medimmune, Merck & Co., Pfizer, Protagonist, Second Genome, Seres, Shire, Theradiag, Amgen, Intestinal Biotech Development, and Genefit. Walter Reinisch has received personal fees as a speaker from Abbott Laboratories, AbbVie, Aesca, Aptalis, Astellas, Centocor, Celltrion, Danone Austria, Elan, Falk Pharma GmbH, Ferring, Immundiagnostik, Mitsubishi Tanabe Pharma Corporation, MSD, Otsuka, PDL, Pharmacosmos, PLS Education, Schering-Plough, Shire, Takeda, Therakos, Vifor, and Yakult; personal fees as a consultant from Abbott Laboratories, AbbVie, Aesca, Amgen, AM Pharma, Astellas, Astra Zeneca, Avaxia, Roland Berger GmbH, Bioclinica, Biogen IDEC, Boehringer Ingelheim, Bristol-Myers Squibb, Cellerix, Chemocentryx, Celgene, Centocor, Celltrion, Covance, Danone Austria, Elan, Ernest & Young, Falk Pharma GmbH, Ferring, Galapagos, Genentech, Gilead, Grünenthal, ICON, Index Pharma, Inova, Janssen, Johnson & Johnson, Kyowa Hakko Kirin Pharma, Lipid Therapeutics, Mallinckrodt, MedImmune, Millennium, Mitsubishi Tanabe Pharma Corporation, MSD, Nestle, Novartis, Ocera, Otsuka, Parexel, PDL, Pharmacosmos, Pfizer, Procter & Gamble, Prometheus, Robarts Clinical Trial, Sandoz, Schering-Plough, Second Genome, Setpointmedical, Sigmoid, Takeda, Therakos, TiGenix, UCB, Vifor, Zealand, Zyngenia, and 4SC; personal fees as an advisor from Abbott Laboratories, AbbVie, Aesca, Amgen, AM Pharma, Astellas, Astra Zeneca, Avaxia, Biogen IDEC, Boehringer Ingelheim, Bristol-Myers Squibb, Cellerix, Chemocentryx, Celgene, Centocor, Celltrion, Danone Austria, Elan, Ferring, Galapagos, Genentech, Grünenthal, Inova, Janssen, Johnson & Johnson, Kyowa Hakko Kirin Pharma, Lipid Therapeutics, MedImmune, Millennium, Mitsubishi Tanabe Pharma Corporation, MSD, Nestle, Novartis, Ocera, Otsuka, PDL, Pharmacosmos, Pfizer, Procter & Gamble, Prometheus, Sandoz, Schering-Plough, Second Genome, Setpointmedical, Takeda, Therakos, TiGenix, UCB, Zealand, Zyngenia, and 4SC; and grants from Abbott Laboratories, AbbVie, Aesca, Centocor, Falk Pharma GmbH, Immundiagnostik, and MSD. Daniel C. Baumgart reports grants, personal fees, and nonfinancial support from Shire, AbbVie, MSD, Takeda, Biogen, Dr. Falk, Ferring, Recordati, Genentech-Roche, Janssen, Pfizer, BMS; personal fees and nonfinancial support from Foreward Pharma and TiGenix; and grants from Nestle, Hitachi, Shield Therapeutics, and Celgene. Axel Dignass reports consultancy fees from AbbVie, MSD, Ferring, Genentech-Roche, Takeda, Pharmacosmos, Vifor, Falk, Mundipharma, Janssen, Allergosan, Hospira, Robarts, Pfizer, Sandoz/Hexal, and Celgene; grants from Institut für Gemeinwohl and Stiftung Leben mit Krebs; payment for lectures from Falk Foundation, Ferring, MSD, AbbVie, Otsuka, Vifor, Immunodiagnostik, Jansen-Cilag, Med Update GmbH, Medice, Pfizer, Mundipharma, Tillotts, and Hospira; manuscript preparation fees from Falk Foundation, Wiley, Thieme, Allergosan, and Takeda; and educational presentation development fees from Pharmacosmos, Falk Foundation, and Tillotts. Maria Nachury has received personal fees from TiGenix and Boehringer Ingelheim; and personal fees and nonfinancial support from AbbVie, MSD, and Takeda. Marc Ferrante has received nonfinancial support from TiGenix; grants, personal fees, and nonfinancial support from Takeda; and personal fees and nonfinancial support from MSD, Janssen, AbbVie, Chiesi, Tillotts, Ferring, Falk, Mitsubishi, Zeria, and Boehringer Ingelheim. Lili Kazemi-Shirazi reports nonfinancial and other support from TiGenix study; other support from SigmaTau and Sanofi; personal fees from MSD, AbbVie, Ferring, MerckSerono/Dr Falk, Chiesi, Novartis, Roche, Abbott, Phadia Austria/Thermo Fisher Scientific, and CSL-Behring; and nonfinancial support from Mylan, Abbott, MSD, Gilead, MerckSerono/Dr Falk, and Novartis. Marie Paule Richard, Mary Carmen Diez, Ignacio Tagarro, and Anne Leselbaum have received personal fees from TiGenix. Silvio Danese has received personal fees from AbbVie, Allergan, Sandoz, UCB, Boehringer Ingelheim. Vifor, Celltrion, Sandoz, MSD, Takeda, Janssen, Mundipharma, Hospira, Ferring, Merck, and Pfizer. Jean C. Grimaud, Fernando de la Portilla, and Eran Goldin declare no competing interests.
Funding This study was sponsored by TiGenix S.A.U. Writing assistance was provided by David Harrison (Cerebellum Communications Ltd.), who was funded by TiGenix S.A.U.