1. Long-term Efficacy and Safety of Stem Cell Therapy (Cx601) for Complex Perianal Fistulas in Patients With Crohn's Disease
- Author
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Julián Panés, Damián García-Olmo, Gert Van Assche, Jean Frederic Colombel, Walter Reinisch, Daniel C. Baumgart, Axel Dignass, Maria Nachury, Marc Ferrante, Lili Kazemi-Shirazi, Jean C. Grimaud, Fernando de la Portilla, Eran Goldin, Marie Paule Richard, Mary Carmen Diez, Ignacio Tagarro, Anne Leselbaum, Silvio Danese, Jean F. Colombel, Anton Stift, Jörg Tschmelitsch, Karl Mrak, Herbert Tilg, Irmgard Kroberger, André D’Hoore, Danny De Looze, Filip Baert, Paul Pattyn, Philippe Zerbib, Frank Zerbib, Stéphanie Viennot, Jean-Louis Dupas, Pierre-Charles Orsoni, Xavier Hebuterne, Amine Rahili, Matthieu Allez, Yves Panis, Max Reinshagen, Roland Scherer, Andreas Sturm, Wolfgang Kruis, Daniel-Simon Duek, Matti Waterman, Adi Lahat-Zok, Oded Zmora, Hagit Tulchinsky, Yair Edden, Antonino Spinelli, Vito Annese, Imerio Angriman, Gabriele Riegler, Francesco Selvaggi, Bas Oldenburg, Lennard Gilissen, Gust Van Montfort, Mark Lowenberg, Adrianus Willem Bemelman, Raúl Almenara, María Dolores Martín Arranz, Mariano García-Arranz, Javier Pérez Gisbert, Rosana Palasí, Carlos Taxonera Samsó, Jose Manuel Herrera Justiniano, Ricardo Rada, Mª Teresa Butrón, Daniel Carpio López, Antonio López-Sanromán, Joaquín Hinojosa de Val, Amparo Solana, F. Xavier González Argenté, Carlos Pastor, Hector Guadalajara, Panes, J, Garcia-Olmo, D, Van Assche, G, Colombel, Jf, Reinisch, W, Baumgart, Dc, Dignass, A, Nachury, M, Ferrante, M, Kazemi-Shirazi, L, Grimaud, Jc, de la Portilla, F, Goldin, E, Richard, Mp, Diez, Mc, Tagarro, I, Leselbaum, A, Danese, S, Panes, J., Garcia-Olmo, D., Van Assche, G., Colombel, J. F., Reinisch, W., Baumgart, D. C., Dignass, A., Nachury, M., Ferrante, M., Kazemi-Shirazi, L., Grimaud, J. C., de la Portilla, F., Goldin, E., Richard, M. P., Diez, M. C., Tagarro, I., Leselbaum, A., Danese, S., Stift, A., Tschmelitsch, J., Mrak, K., Tilg, H., Kroberger, I., D'Hoore, A., De Looze, D., Baert, F., Pattyn, P., Zerbib, P., Zerbib, F., Viennot, S., Dupas, J. -L., Orsoni, P. -C., Hebuterne, X., Rahili, A., Allez, M., Panis, Y., Reinshagen, M., Scherer, R., Sturm, A., Kruis, W., Duek, D. -S., Waterman, M., Lahat-Zok, A., Zmora, O., Tulchinsky, H., Edden, Y., Spinelli, A., Annese, V., Angriman, I., Riegler, G., Selvaggi, F., Oldenburg, B., Gilissen, L., Van Montfort, G., Lowenberg, M., Bemelman, A. W., Almenara, R., Martin Arranz, M. D., Garcia-Arranz, M., Perez Gisbert, J., Palasi, R., Samso, C. T., Herrera Justiniano, J. M., Rada, R., Butron, M. T., Lopez, D. C., Lopez-Sanroman, A., Hinojosa de Val, J., Solana, A., Gonzalez Argente, F. X., Pastore, Concetta, Guadalajara, H., Gastroenterology and Hepatology, and AGEM - Digestive immunity
- Subjects
Male ,Time Factors ,Intention to Treat Analysi ,medicine.medical_treatment ,Gastroenterology ,0302 clinical medicine ,Crohn Disease ,Risk Factors ,Clinical endpoint ,Israel ,Transplantation, Homologou ,Crohn's disease ,education.field_of_study ,medicine.diagnostic_test ,Remission Induction ,Stem-cell therapy ,Magnetic Resonance Imaging ,Intention to Treat Analysis ,Europe ,Treatment Outcome ,Adipose Tissue ,030220 oncology & carcinogenesis ,030211 gastroenterology & hepatology ,Female ,Clinical Remission ,Human ,Adult ,Homologous ,medicine.medical_specialty ,Time Factor ,Population ,Placebo ,03 medical and health sciences ,Double-Blind Method ,Internal medicine ,medicine ,Transplantation, Homologous ,Humans ,Rectal Fistula ,education ,Adverse effect ,Transplantation ,Intention-to-treat analysis ,Hepatology ,business.industry ,Risk Factor ,Cell Therapy ,Magnetic resonance imaging ,Anal Fistula ,Combined Remission ,Stem Cell Transplantation ,medicine.disease ,business - Abstract
Background & Aims: Therapies for perianal fistulas in patients with Crohn's disease are often ineffective in producing long-term healing. We performed a randomized placebo-controlled trial to determine the long-term efficacy and safety of a single local administration of allogeneic expanded adipose-derived stem cells (Cx601) in patients with Crohn's disease and perianal fistulas. Methods: We performed a double-blind study at 49 hospitals in Europe and Israel, comprising 212 patients with Crohn's disease and treatment-refractory, draining, complex perianal fistulas. Patients were randomly assigned (1:1) to groups given a single local injection of 120 million Cx601 cells or placebo (control), in addition to the standard of care. Efficacy endpoints evaluated in the modified intention-to-treat population (randomly assigned, treated, and with 1 or more post-baseline efficacy assessment) at week 52 included combined remission (closure of all treated external openings draining at baseline with absence of collections >2 cm, confirmed by magnetic resonance imaging) and clinical remission (absence of draining fistulas). Results: The study's primary endpoint, at week 24, was previously reported (combined remission in 51.5% of patients given Cx601 vs 35.6% of controls, for a difference of 15.8 percentage points; 97.5% confidence interval [CI] 0.5–31.2; P =.021). At week 52, a significantly greater proportion of patients given Cx601 achieved combined remission (56.3%) vs controls (38.6%) (a difference of 17.7 percentage points; 95% CI 4.2–31.2; P =.010), and clinical remission (59.2% vs 41.6% of controls, for a difference of 17.6 percentage points; 95% CI 4.1–31.1; P =.013). Safety was maintained throughout week 52; adverse events occurred in 76.7% of patients in the Cx601 group and 72.5% of patients in the control group. Conclusion: In a phase 3 trial of patients with Crohn's disease and treatment-refractory complex perianal fistulas, we found Cx601 to be safe and effective in closing external openings, compared with placebo, after 1 year. ClinicalTrials.gov no: NCT01541579.
- Published
- 2018
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