Long-term Efficacy and Safety of Stem Cell Therapy (Cx601) for Complex Perianal Fistulas in Patients With Crohn's Disease

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; Anton Stift; J. rg 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; M. Teresa Butrón; Daniel Carpio López; Antonio López-Sanromán; Joaquín Hinojosa de Val; Amparo Solana; F. Xavier González Argenté; Carlos Pastor; Hector Guadalajara

doi:https://doi.org/10.1053/j.gastro.2017.12.020

Long-term Efficacy and Safety of Stem Cell Therapy (Cx601) for Complex Perianal Fistulas in Patients With Crohn's Disease

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, Anton Stift, J. rg TschmelitschKarl 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, M. Teresa Butrón, Daniel Carpio López, Antonio López-Sanromán, Joaquín Hinojosa de Val, Amparo Solana, F. Xavier González Argenté, Carlos Pastor, Hector Guadalajara

Gastroenterology and Hepatology (AMC)

Research output: Contribution to journal › Article › Academic › peer-review

314 Citations (Scopus)

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.

Original language	English
Pages (from-to)	1334-1342.e4
Journal	Gastroenterology
Volume	154
Issue number	5
DOIs	https://doi.org/10.1053/j.gastro.2017.12.020
Publication status	Published - 2018

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https://doi.org/10.1053/j.gastro.2017.12.020

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Panés, J., García-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., ... Guadalajara, H. (2018). Long-term Efficacy and Safety of Stem Cell Therapy (Cx601) for Complex Perianal Fistulas in Patients With Crohn's Disease. Gastroenterology, 154(5), 1334-1342.e4. https://doi.org/10.1053/j.gastro.2017.12.020

@article{53e4dac175e94f0cb4ac4ce40e400c1d,

title = "Long-term Efficacy and Safety of Stem Cell Therapy (Cx601) for Complex Perianal Fistulas in Patients With Crohn's Disease",

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.",

author = "Juli{\'a}n Pan{\'e}s and Dami{\'a}n Garc{\'i}a-Olmo and {van Assche}, Gert and Colombel, {Jean Frederic} and Walter Reinisch and Baumgart, {Daniel C.} and Axel Dignass and Maria Nachury and Marc Ferrante and Lili Kazemi-Shirazi and Grimaud, {Jean C.} and {de la Portilla}, Fernando and Eran Goldin and Richard, {Marie Paule} and Diez, {Mary Carmen} and Ignacio Tagarro and Anne Leselbaum and Silvio Danese and Anton Stift and Tschmelitsch, {J. rg} and Karl Mrak and Herbert Tilg and Irmgard Kroberger and Andr{\'e} D'Hoore and {de Looze}, Danny and Filip Baert and Paul Pattyn and Philippe Zerbib and Frank Zerbib and St{\'e}phanie Viennot and Jean-Louis Dupas and Pierre-Charles Orsoni and Xavier Hebuterne and Amine Rahili and Matthieu Allez and Yves Panis and Max Reinshagen and Roland Scherer and Andreas Sturm and Wolfgang Kruis and Daniel-Simon Duek and Matti Waterman and Adi Lahat-Zok and Oded Zmora and Hagit Tulchinsky and Yair Edden and Antonino Spinelli and Vito Annese and Imerio Angriman and Gabriele Riegler and Francesco Selvaggi and Bas Oldenburg and Lennard Gilissen and {van Montfort}, Gust and Mark Lowenberg and Bemelman, {Adrianus Willem} and Ra{\'u}l Almenara and {Mart{\'i}n Arranz}, {Mar{\'i}a Dolores} and Mariano Garc{\'i}a-Arranz and {P{\'e}rez Gisbert}, Javier and Rosana Palas{\'i} and Sams{\'o}, {Carlos Taxonera} and {Herrera Justiniano}, {Jose Manuel} and Ricardo Rada and Butr{\'o}n, {M. Teresa} and L{\'o}pez, {Daniel Carpio} and Antonio L{\'o}pez-Sanrom{\'a}n and {Hinojosa de Val}, Joaqu{\'i}n and Amparo Solana and {Gonz{\'a}lez Argent{\'e}}, {F. Xavier} and Carlos Pastor and Hector Guadalajara",

year = "2018",

doi = "https://doi.org/10.1053/j.gastro.2017.12.020",

language = "English",

volume = "154",

pages = "1334--1342.e4",

journal = "Gastroenterology",

issn = "0016-5085",

publisher = "W.B. Saunders Ltd",

number = "5",

}

Panés, J, García-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, Stift, A, Tschmelitsch, JR, 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, AW, Almenara, R, Martín Arranz, MD, García-Arranz, M, Pérez Gisbert, J, Palasí, R, Samsó, CT, Herrera Justiniano, JM, Rada, R, Butrón, MT, López, DC, López-Sanromán, A, Hinojosa de Val, J, Solana, A, González Argenté, FX, Pastor, C & Guadalajara, H 2018, 'Long-term Efficacy and Safety of Stem Cell Therapy (Cx601) for Complex Perianal Fistulas in Patients With Crohn's Disease', Gastroenterology, vol. 154, no. 5, pp. 1334-1342.e4. https://doi.org/10.1053/j.gastro.2017.12.020

TY - JOUR

T1 - Long-term Efficacy and Safety of Stem Cell Therapy (Cx601) for Complex Perianal Fistulas in Patients With Crohn's Disease

AU - Panés, Julián

AU - García-Olmo, Damián

AU - van Assche, Gert

AU - Colombel, Jean Frederic

AU - Reinisch, Walter

AU - Baumgart, Daniel C.

AU - Dignass, Axel

AU - Nachury, Maria

AU - Ferrante, Marc

AU - Kazemi-Shirazi, Lili

AU - Grimaud, Jean C.

AU - de la Portilla, Fernando

AU - Goldin, Eran

AU - Richard, Marie Paule

AU - Diez, Mary Carmen

AU - Tagarro, Ignacio

AU - Leselbaum, Anne

AU - Danese, Silvio

AU - Stift, Anton

AU - Tschmelitsch, J. rg

AU - Mrak, Karl

AU - Tilg, Herbert

AU - Kroberger, Irmgard

AU - D'Hoore, André

AU - de Looze, Danny

AU - Baert, Filip

AU - Pattyn, Paul

AU - Zerbib, Philippe

AU - Zerbib, Frank

AU - Viennot, Stéphanie

AU - Dupas, Jean-Louis

AU - Orsoni, Pierre-Charles

AU - Hebuterne, Xavier

AU - Rahili, Amine

AU - Allez, Matthieu

AU - Panis, Yves

AU - Reinshagen, Max

AU - Scherer, Roland

AU - Sturm, Andreas

AU - Kruis, Wolfgang

AU - Duek, Daniel-Simon

AU - Waterman, Matti

AU - Lahat-Zok, Adi

AU - Zmora, Oded

AU - Tulchinsky, Hagit

AU - Edden, Yair

AU - Spinelli, Antonino

AU - Annese, Vito

AU - Angriman, Imerio

AU - Riegler, Gabriele

AU - Selvaggi, Francesco

AU - Oldenburg, Bas

AU - Gilissen, Lennard

AU - van Montfort, Gust

AU - Lowenberg, Mark

AU - Bemelman, Adrianus Willem

AU - Almenara, Raúl

AU - Martín Arranz, María Dolores

AU - García-Arranz, Mariano

AU - Pérez Gisbert, Javier

AU - Palasí, Rosana

AU - Samsó, Carlos Taxonera

AU - Herrera Justiniano, Jose Manuel

AU - Rada, Ricardo

AU - Butrón, M. Teresa

AU - López, Daniel Carpio

AU - López-Sanromán, Antonio

AU - Hinojosa de Val, Joaquín

AU - Solana, Amparo

AU - González Argenté, F. Xavier

AU - Pastor, Carlos

AU - Guadalajara, Hector

PY - 2018

Y1 - 2018

N2 - 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.

AB - 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.

UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85043344645&origin=inward

UR - https://www.ncbi.nlm.nih.gov/pubmed/29277560

U2 - https://doi.org/10.1053/j.gastro.2017.12.020

DO - https://doi.org/10.1053/j.gastro.2017.12.020

M3 - Article

C2 - 29277560

SN - 0016-5085

VL - 154

SP - 1334-1342.e4

JO - Gastroenterology

JF - Gastroenterology

IS - 5

ER -

Long-term Efficacy and Safety of Stem Cell Therapy (Cx601) for Complex Perianal Fistulas in Patients With Crohn's Disease

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