Real-world evidence of tofacitinib effectiveness and safety in patients with refractory ulcerative colitis.


Journal

Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver
ISSN: 1878-3562
Titre abrégé: Dig Liver Dis
Pays: Netherlands
ID NLM: 100958385

Informations de publication

Date de publication:
03 2020
Historique:
received: 07 08 2019
revised: 07 10 2019
accepted: 08 10 2019
pubmed: 17 11 2019
medline: 21 1 2021
entrez: 17 11 2019
Statut: ppublish

Résumé

Phase III trials demonstrated effectiveness of tofacitinib, an oral Janus kinase inhibitor, to induce and maintain remission in patients with moderate-to-severe active ulcerative colitis (UC). We report the real-world effectiveness and safety of tofacitinib in patients with UC in France. From February 2017 to December 2018, we performed a national French cohort study, which included all consecutive patients with an active UC refractory to anti-TNF and vedolizumab, who received tofacitinib. Outcomes were survival without colectomy, survival without tofacitinib discontinuation and steroid-free clinical remission at weeks 14, 24 and 48. Thirty-eight patients were included, with a median follow-up of 41.5 (18.5-56.8) weeks. Survival without colectomy was 77% [95% confidence interval (95%CI): 59.3-87.9] at week 24 and 70% (95%CI: 50.9-82.8) at week 48. Survival without treatment discontinuation was 70% (95%CI: 52.6-82.3) at week 24. Steroid-free clinical remission was observed in 13 (34%) patients at week 48. Adverse events occurred in 14 (37%) patients, including 6 severe adverse events and three herpes zoster infections. In a highly refractory UC population, one third of patients treated with tofacitinib achieved steroid-free clinical remission at week 14 and 70% of patients avoided colectomy at one year, with an acceptable safety profile. These data confirm tofacitinib effectiveness in UC, especially after multiple biologic failures.

Sections du résumé

BACKGROUND
Phase III trials demonstrated effectiveness of tofacitinib, an oral Janus kinase inhibitor, to induce and maintain remission in patients with moderate-to-severe active ulcerative colitis (UC).
AIMS
We report the real-world effectiveness and safety of tofacitinib in patients with UC in France.
METHODS
From February 2017 to December 2018, we performed a national French cohort study, which included all consecutive patients with an active UC refractory to anti-TNF and vedolizumab, who received tofacitinib. Outcomes were survival without colectomy, survival without tofacitinib discontinuation and steroid-free clinical remission at weeks 14, 24 and 48.
RESULTS
Thirty-eight patients were included, with a median follow-up of 41.5 (18.5-56.8) weeks. Survival without colectomy was 77% [95% confidence interval (95%CI): 59.3-87.9] at week 24 and 70% (95%CI: 50.9-82.8) at week 48. Survival without treatment discontinuation was 70% (95%CI: 52.6-82.3) at week 24. Steroid-free clinical remission was observed in 13 (34%) patients at week 48. Adverse events occurred in 14 (37%) patients, including 6 severe adverse events and three herpes zoster infections.
CONCLUSION
In a highly refractory UC population, one third of patients treated with tofacitinib achieved steroid-free clinical remission at week 14 and 70% of patients avoided colectomy at one year, with an acceptable safety profile. These data confirm tofacitinib effectiveness in UC, especially after multiple biologic failures.

Identifiants

pubmed: 31732444
pii: S1590-8658(19)30844-8
doi: 10.1016/j.dld.2019.10.003
pii:
doi:

Substances chimiques

Antibodies, Monoclonal, Humanized 0
Janus Kinase Inhibitors 0
Piperidines 0
Pyrimidines 0
Tumor Necrosis Factor Inhibitors 0
tofacitinib 87LA6FU830
vedolizumab 9RV78Q2002

Types de publication

Journal Article Multicenter Study Observational Study

Langues

eng

Sous-ensembles de citation

IM

Pagination

268-273

Informations de copyright

Copyright © 2019 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Auteurs

Loriane Lair-Mehiri (L)

AP-HP, Hôpital Beaujon, Service de gastro-entérologie-MICI, Inserm et Université Paris Diderot, Clichy, France.

Carmen Stefanescu (C)

AP-HP, Hôpital Beaujon, Service de gastro-entérologie-MICI, Inserm et Université Paris Diderot, Clichy, France.

Thibaut Vaysse (T)

AP-HP, Hôpital du Kremlin-Bicêtre, Service de gastro-entérologie, Université Paris Sud, France.

David Laharie (D)

CHU de Bordeaux, Hôpital Haut-Lévêque, Service d'hépato-gastro-entérologie, Univ. Bordeaux, Pessac, France.

Xavier Roblin (X)

CHU de Saint-Etienne, Hôpital Bellevue, Saint-Etienne Cedex 2, France.

Isabelle Rosa (I)

Centre Hospitalier Intercommunal de Créteil, Service de gastro-entérologie, Créteil, France.

Xavier Treton (X)

AP-HP, Hôpital Beaujon, Service de gastro-entérologie-MICI, Inserm et Université Paris Diderot, Clichy, France.

Vered Abitbol (V)

AP-HP, Hôpital Cochin, Service de gastro-entérologie, Paris, France.

Aurélien Amiot (A)

AP-HP, Hôpital Henri Mondor, Service de gastro-entérologie, Université Paris Est-Créteil, Créteil, France.

Guillaume Bouguen (G)

CHU de Rennes, Hôpital Pontchaillou, Service d'hépato-gastro-entérologie, Rennes, France.

Nina Dib (N)

CHU d'Angers, Service d'hépato-gastro-entérologie, Angers, France.

Mathurin Fumery (M)

CHU Amiens-Picardie, Service d'hépato-gastro-entérologie-Rond point du Pr Cabrol et Peritox, UFR Médecine, Amiens, France.

Benjamin Pariente (B)

CHRU de Lille, Hôpital Claude Huriez, Service des maladies de l'appareil digestif, Lille Cedex, France.

Franck Carbonnel (F)

AP-HP, Hôpital du Kremlin-Bicêtre, Service de gastro-entérologie, Université Paris Sud, France.

Laurent Peyrin-Biroulet (L)

CHU de Nancy, Hôpital de Nancy, Service d'hépato-gastro-entérologie, Nancy Cedex, France.

Marion Simon (M)

Institut Mutualiste Montsouris, Service d'hépato-gastro-entérologie, Paris, France.

Stéphanie Viennot (S)

CHU de Caen Normandie, Hôpital Clemenceau, Service d'hépato-gastro-entérologie, Caen, France.

Yoram Bouhnik (Y)

AP-HP, Hôpital Beaujon, Service de gastro-entérologie-MICI, Inserm et Université Paris Diderot, Clichy, France. Electronic address: yoram.bouhnik@aphp.fr.

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