Methotrexate Is Not Superior to Placebo for Inducing Steroid-Free Remission, but Induces Steroid-Free Clinical Remission in a Larger Proportion of Patients With Ulcerative Colitis.

Détails

ID Serval
serval:BIB_C02C08935AFF
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Methotrexate Is Not Superior to Placebo for Inducing Steroid-Free Remission, but Induces Steroid-Free Clinical Remission in a Larger Proportion of Patients With Ulcerative Colitis.
Périodique
Gastroenterology
Auteur(s)
Carbonnel F., Colombel J.F., Filippi J., Katsanos K.H., Peyrin-Biroulet L., Allez M., Nachury M., Novacek G., Danese S., Abitbol V., Bossa F., Moreau J., Bommelaer G., Bourreille A., Fumery M., Roblin X., Reinisch W., Bouhnik Y., Brixi H., Seksik P., Malamut G., Färkkilä M., Coulibaly B., Dewit O., Louis E., Deplanque D., Michetti P., Sarter H., Laharie D., European Crohn's, Colitis Organisation
Collaborateur(s)
Groupe d'Étude Thérapeutique des Affections Inflammatoires Digestives
Contributeur(s)
European Crohn's, Colitis Organisation, Demolin J., Détré P., Brillaut£££Gaëlle£££ G. 
ISSN
1528-0012 (Electronic)
ISSN-L
0016-5085
Statut éditorial
Publié
Date de publication
2016
Peer-reviewed
Oui
Volume
150
Numéro
2
Pages
380-8.e4
Langue
anglais
Notes
Publication types: Journal Article ; Multicenter Study ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
BACKGROUND & AIMS: Parenteral methotrexate is an effective treatment for patients with Crohn's disease, but has never been adequately evaluated in patients with ulcerative colitis (UC). We conducted a randomized controlled trial to determine its safety and efficacy in patients with steroid-dependent UC.
METHODS: We performed a double-blind, placebo-controlled trial to evaluate the efficacy of parenteral methotrexate (25 mg/wk) in 111 patients with corticosteroid-dependent UC at 26 medical centers in Europe from 2007 through 2013. Patients were given prednisone (10 to 40 mg/d) when the study began and were randomly assigned to groups (1:1) given placebo or methotrexate (intramuscularly or subcutaneously, 25 mg weekly) for 24 weeks. The primary end point was steroid-free remission (defined as a Mayo score ≤2 with no item >1 and complete withdrawal of steroids) at week 16. Secondary endpoints included clinical remission (defined as a Mayo clinical subscore ≤2 with no item >1) and endoscopic healing without steroids at weeks 16 and/or 24, remission without steroids at week 24, and remission at both weeks 16 and 24.
RESULTS: Steroid-free remission at week 16 was achieved by 19 of 60 patients given methotrexate (31.7%) and 10 of 51 patients given placebo (19.6%)--a difference of 12.1% (95% confidence interval [CI]: -4.0% to 28.1%; P = .15). The proportion of patients in steroid-free clinical remission at week 16 was 41.7% in the methotrexate group and 23.5% in the placebo group, for a difference of 18.1% (95% CI: 1.1% to 35.2%; P = .04). The proportions of patients with steroid-free endoscopic healing at week 16 were 35% in the methotrexate group and 25.5% in the placebo group--a difference of 9.5% (95% CI: -7.5% to 26.5%; P = .28). No differences were observed in other secondary end points. More patients receiving placebo discontinued the study because of adverse events (47.1%), mostly caused by UC, than patients receiving methotrexate (26.7%; P = .03). A higher proportion of patients in the methotrexate group had nausea and vomiting (21.7%) than in the placebo group (3.9%; P = .006).
CONCLUSIONS: In a randomized controlled trial, parenteral methotrexate was not superior to placebo for induction of steroid-free remission in patients with UC. However, methotrexate induced clinical remission without steroids in a significantly larger percentage of patients, resulting in fewer withdrawals from therapy due to active UC. ClinicalTrials.gov ID NCT00498589.
Mots-clé
Adrenal Cortex Hormones/adverse effects, Adrenal Cortex Hormones/therapeutic use, Adult, Anti-Inflammatory Agents/administration & dosage, Anti-Inflammatory Agents/adverse effects, Colitis, Ulcerative/diagnosis, Colitis, Ulcerative/drug therapy, Colon/drug effects, Colon/pathology, Double-Blind Method, Drug Therapy, Combination, Europe, Female, Gastrointestinal Agents/administration & dosage, Gastrointestinal Agents/adverse effects, Humans, Injections, Intramuscular, Injections, Subcutaneous, Male, Methotrexate/administration & dosage, Methotrexate/adverse effects, Middle Aged, Remission Induction, Time Factors, Treatment Outcome, Wound Healing/drug effects
Pubmed
Web of science
Création de la notice
19/02/2016 20:57
Dernière modification de la notice
03/03/2018 21:05
Données d'usage