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

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• 作者：Franck Carbonnel¹ ; ² ; ^{fcarbonnel7@gmail.com" class="auth_mail" title="E-mail the corresponding author} ; Jean Fré ; dé ; ric Colombel³ ; Jé ; rome Filippi⁴ ; Konstantinos H. Katsanos⁵ ; Laurent Peyrin-Biroulet⁶ ; Mathieu Allez⁷ ; Maria Nachury² ; ⁸ ; Gottfried Novacek⁹ ; Silvio Danese¹⁰ ; Vered Abitbol¹¹ ; Fabrizio Bossa¹² ; Jacques Moreau¹³ ; Gilles Bommelaer¹⁴ ; Arnaud Bourreille¹⁵ ; Mathurin Fumery¹⁶ ; Xavier Roblin¹⁷ ; Walter Reinisch⁹ ; ¹⁸ ; Yoram Bouhnik¹⁹ ; Hedia Brixi²⁰ ; Philippe Seksik²¹ ; Georgia Malamut²² ; Martti Fä ; rkkilä ; ²³ ; Baya Coulibaly²⁴ ; Olivier Dewit²⁵ ; Edouard Louis²⁶ ; Dominique Deplanque²⁷ ; Pierre Michetti²⁸ ; ^&lowast ; ; Hé ; lè ; ne Sarter²⁹ ; ^&lowast ; ; David Laharie³⁰ ; European Crohn's ; Colitis Organisation ; the Groupe d&rsquo ; É ; tude Thé ; rapeutique des Affections Inflammatoires DigestivesJulie Demolin ; Patricia Dé ; tré ; Gaë ; lle Brillaut
• 关键词：IBD ; Methotrexate ; Clinical Trial ; Drug
• 刊名：Gastroenterology
• 出版年：2016
• 出版时间：February 2016
• 年：2016
• 卷：150
• 期：2
• 页码：380-388.e4
• 全文大小：602 K

文摘

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.