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Gastroenterology. 2018 Apr;154(5):1334-1342.e4. doi: 10.1053/j.gastro.2017.12.020. Epub 2017 Dec 24.

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

Author information

1
Department of Gastroenterology, Hospital Clínic, IDIBAPS, CIBERehd, Barcelona, Spain. Electronic address: jpanes@clinic.cat.
2
Department of Surgery, Hospital U. Fundación Jiménez Díaz, Madrid, Spain.
3
Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Leuven, Belgium.
4
Department of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York.
5
Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria; McMaster University, Hamilton, Ontario, Canada.
6
Department of Gastroenterology and Hepatology, Charité Medical School - Humboldt-University of Berlin, Berlin, Germany.
7
Department of Medicine I, Agaplesion Markus Hospital, Frankfurt, Germany.
8
Department of Gastroenterology and Hepatology, CHU Lille, Lille, France.
9
Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria.
10
Department of Hepato-Gastroenterology, Hôpital Nord, Marseille, France.
11
Department of Surgery, Unit of Coloproctology, University Virgen del Rocio Hospital/IBiS/CSIC/University of Seville, Seville, Spain.
12
Digestive Diseases Institute, Sharee Zedek MC, Jerusalem, Israel.
13
TiGenix, Parque Tecnológico de Madrid, Madrid, Spain.
14
TiGenix, Parque Tecnológico de Madrid, Madrid, Spain; CDD-Clinical Drug Development, S.L., Barcelona, Spain.
15
Department of Gastroenterology, Istituto Clinico Humanitas IRCCS, Milano, Italy.

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.

KEYWORDS:

Anal Fistula; Cell Therapy; Clinical Remission; Combined Remission

PMID:
29277560
DOI:
10.1053/j.gastro.2017.12.020
[Indexed for MEDLINE]

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