Effectiveness and safety of methotrexate monotherapy in patients with Crohn’s disease refractory to anti‐TNF‐α: results from the ENEIDA registry

Abstract

SummaryBackgroundMethotrexate can be used to maintain remission in Crohn's disease patients who are intolerant to thiopurines. Data on its use as monotherapy in other scenarios are limited.AimTo assess the effectiveness of methotrexate monotherapy in Crohn's disease patients after previous failure to anti‐tumour necrosis factor (anti‐TNFα) drugs.MethodsA retrospective, observational multicentre study of data from the Spanish ENEIDA registry. Participants were patients with active Crohn's disease and previous failure to anti‐TNFα started on methotrexate monotherapy. Short‐term effectiveness was assessed at 12‐16 weeks based on Harvey‐Bradshaw index (HBI): clinical remission as HBI ≤ 3 points and clinical response as HBI drop of ≥ 3 points over baseline. Long‐term effectiveness was defined as steroid‐free methotrexate persistence from 12 to 16 weeks until maximum follow up. Adverse events were recorded.ResultsData were compiled for 110 patients treated with methotrexate after a failed response to one (39%) or two (55.6%) anti‐TNFα agents. Short‐term clinical response and remission rates were 60% and 30.9% respectively. Of 74 patients who continued after week 16, long‐term effectiveness was achieved in 82% and 74% at 12 and 24 months respectively. In the multivariate analysis, non‐remission at short term (vs remission) was associated with long‐term failure (HR 2.58, 95%CI 1.95‐3.68, P = 0.028). Adverse events (evaluated in 100 patients) were recorded in 44%, and in 30.4% of these patients, they led to methotrexate discontinuation.ConclusionsThe benefits observed suggest methotrexate monotherapy could be a valid option in Crohn's disease patients with previous failure to anti‐TNFα.

Effectiveness and tolerability of methotrexate monotherapy in Crohn’s disease patients: a multicenter observational study

“…Additionally, they reported a long-term clinical effectiveness of 82% and 74% at 12 and 24 months, respectively. 21 Furthermore, they determined that short-term clinical remission at 12–16 weeks is significantly associated with long-term MTX maintenance. 21 Reports on the mucosal healing rate of MTX monotherapy in CD patients are scarce.…”

The Effectiveness and Safety of Methotrexate as the First-Line Immunomodulator of Maintenance Therapy in Pediatric Crohn Disease

“…Although MTX is not yet recommended as the irst immunomodulator in the latest guidelines for adult CD (19)(20)(21)(22), its efectiveness in TP-naïve adult CD patients has already been reported (23)(24)(25). The efectiveness of MTX to maintain a remission state as a secondary immunomodulator after TP failure or intolerance was already documented in multiple pediatric studies (15,16,(26)(27)(28)(29)(30)(31)(32)(33)(34). However, to date, there are only a few studies on the therapeutic role of MTX as a irst-line immunomodulator in TP-naïve CD patients (11,35,36), even though the latest guideline for pediatric CD published in 2021 recommended both TP and MTX for maintenance therapy (1).…”

Modern strategies and prospects for the treatment of ulcerative colitis

“…Mesonero F. и соавторы показали, что монотерапия метотрексатом сопоставима с препаратами против фактора некроза опухоли (при их непереносимости): долгосрочная эффективность метотрексата составила 82% в течение года, 74% через два года терапии [11]. Метотрексат достаточно эффективен в индукции и поддержании ремиссии ЯК, начинает действовать в течение первых 3-4 недель, однако его противорецидивный эффект уступает азатиоприну [6].…”

“…С целью профилактики развития нежелательных явлений после приёма метотрексата следует принять фолиевую кислоту. Препараты, направленные против фактора некроза опухоли (ФНО), зачастую используют совместно с метотрексатом, так метотрексат уменьшает резистентность к инфликсимабу и адалимумабу за счёт подавления синтеза к нему антител, соответственно замедляется элиминация этого препарата [11].…”

“…Адалимумаб блокирует активный центр ФНО-альфа посредством взаимодействия с р55 и р75 рецепторами [16]. Помимо анти-ФНО активности, адалимумаб снижает концентрации молекул адгезии, металлопротеиназ и IL-6, которые принимают активное участие в генерации воспаления [11]. Снижение хемоатракции способствует уменьшению миграционной способности лимфоцитов.…”