Recomendaciones del Grupo Español de Trabajo de Enfermedad de Crohn y Colitis Ulcerosa (GETECCU) sobre el uso de metotrexato en la enfermedad inflamatoria intestinal

Gomollón, Fernando; Rubio, Saioa; Charro, Mara; García-López, Santiago; Muñoz, Fernándo; Gisbert, Javier P.; Domènech, Eugeni

doi:10.1016/j.gastrohep.2014.10.002

Cited by 19 publications

(7 citation statements)

References 76 publications

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“…To date, only the Spanish Working Group on Crohn's Disease and Ulcerative Colitis has developed consensus guidelines regarding pre-treatment assessment and treatment monitoring when using methotrexate in patients with Crohn's disease [40]. Given the existing evidence, including our study, whether the best approach to monitoring methotrexate-induced liver fibrosis is transient elastography or a combination of a biochemical test and transient elastography with liver biopsies indicated when discordant, whether these tests should be routinely performed on all methotrexate-treated patients or only on those with a known risk or pre-existing NALFD, and the best cutoff for significant fibrosis in methotrexate-induced hepatotoxicity, all remain to be established, though it seems that the risk is globally low.…”

Section: Discussionmentioning

confidence: 99%

Noninvasive assessment of liver fibrosis in Crohn’s disease patients exposed to methotrexate

Llaó

Masnou

Romero

et al. 2020

European Journal of Gastroenterology &Amp; Hepatology

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Background: Methotrexate is widely used to treat some inflammatory chronic disorders, though it is hampered by the risk of liver fibrosis. Many recommendations have been made to assess methotrexate-related hepatotoxicity, including liver biopsy. However, other noninvasive methods to assess liver fibrosis have been developed and could be implemented for patients treated with methotrexate. Aim: The aim of the study was to compare the prevalence of liver fibrosis by means of noninvasive methods [aspartate transaminase-to-platelet ratio index (APRI) Forns index, and transient elastography] in patients with Crohn’s disease exposed or not to methotrexate, and to identify risk factors for liver fibrosis. Methods: Prospective, cross-sectional study. All patients with Crohn’s disease exposed to methotrexate were included and compared to an unselected cohort of outpatients with Crohn’s disease never exposed to methotrexate. Results: A total of 84 patients with Crohn’s disease, 56 exposed to methotrexate, and 28 controls, were included. Significant liver fibrosis was found in 7% of methotrexate-exposed patients with Crohn’s disease and 10% of controls as measured by transient elastography, and in 7% of controls as measured by the Forns index. No cases of liver fibrosis were detected by APRI. Only alcohol consumption, diabetes mellitus, and age were associated with significant liver fibrosis. Conclusions: Significant liver fibrosis is uncommon among patients with Crohn’s disease, even among those exposed to methotrexate. The risk of liver fibrosis in Crohn’s disease seems to depend on common risk factors for liver disease.

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Section: Discussionmentioning

confidence: 99%

Noninvasive assessment of liver fibrosis in Crohn’s disease patients exposed to methotrexate

Llaó

Masnou

Romero

et al. 2020

European Journal of Gastroenterology &Amp; Hepatology

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“…Patients were identified from the ENEIDA registry. Inclusion criteria were CD diagnosis, age over 18 years of age, MTX use exclusively in monotherapy for induction of remission and maintenance therapy in active CD (according to clinically recommended doses) 6,7 and available DNA sample. The data collected in the present study included demographic data, age at diagnosis, smoking habit, duration of CD at the time MTX was first prescribed, disease location and behaviour, perianal disease, extraintestinal manifestations, CD-related abdominal surgeries and medical therapy (both immunosuppressants and biological therapy), including indication, dosage, treatment duration and drug-related adverse events.…”

Section: Study Populationmentioning

confidence: 99%

“…Parenteral MTX has shown effectiveness for inducing and maintaining clinical remission in several studies assessing the efficacy of this drug for steroiddependent and steroid-resistant CD. 6,7 Moreover, concomitant use of MTX with infliximab also reduces the development of antibodies to infliximab. 8 In spite of its efficacy, MTX is currently used as immunosuppressant therapy in steroid-dependent patients with moderateto-severe CD only when thiopurines have either failed, are not tolerated or are contraindicated.…”

Section: Introductionmentioning

confidence: 99%

“…8 In spite of its efficacy, MTX is currently used as immunosuppressant therapy in steroid-dependent patients with moderateto-severe CD only when thiopurines have either failed, are not tolerated or are contraindicated. 6 The most commonly described MTXrelated adverse events include dyspnoea, nausea, vomiting, fatigue, liver fibrosis and myelotoxicity. 9 It has been reported that up to 45% of patients may develop these adverse events and, although most of them are not life threatening, they prompt MTX discontinuation in up to 17% of patients.…”

Section: Introductionmentioning

confidence: 99%

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Genetic biomarkers of methotrexate response and safety in Crohn's disease: Data from the Spanish ENEIDA registry

Salazar,

Garcia‐Planella,

Fernández‐Clotet

et al. 2024

Brit J Clinical Pharma

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AimsMethotrexate (MTX) is used to induce and maintain remission in patients with steroid‐dependent Crohn's disease (CD). Despite its proven efficacy, its use is limited due to associated adverse events. Polymorphisms involving folate pathway genes might influence MTX efficacy and toxicity. We aimed to assess the impact of certain polymorphisms on the therapeutic outcomes of MTX in CD.MethodsPatients with CD who exclusively followed MTX monotherapy and fulfilled inclusion criteria were identified from the GETECCU ENEIDA registry. Variants of ATIC, DHFR, MTHFR, SLC19A1, ABCB1 and ABCC3 genes were analysed and their association with efficacy and toxicity was assessed.ResultsA total of 129 patients were included in the analysis. MTX was used at a median weekly dose of 25 mg (interquartile range, 15–25 mg) and a median time of 14 months (interquartile range, 4–52 months). Thirty‐seven percent of the patients achieved disease remission with MTX monotherapy, while 34% were nonresponders (MTX failure). MTX‐related toxicity occurred in 40 patients (30%), leading to MTX discontinuation in 19%. DHFR rs408626 (odds ratio [OR] 3.12, 95% confidence interval [CI] 1.22–7.69; P = .017) and MTHFR rs1801133 (OR 2.86, 95% CI 1.23–6.68; P = .015) variants, and smoking (OR 2.61, 95% CI 1.12–6.05; P = .026) were associated with a higher risk of MTX failure. Additionally, the MTHFR rs1801131 variant was associated with a higher risk of MTX‐related adverse effects (OR 2.78, 95% CI 1.26–6.13, P = .011).ConclusionOur study shows that variants of MTHFR and DHFR genes may be associated with MTX efficacy and adverse events in patients with CD.

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“…At varying doses, by different routes of administration, at various stages of each of the diseases and applied alone or in combination with other medications, the following are some of the current indications of MTX: rheumatoid arthritis, psoriasis, atopic dermatitis, Crohn's disease, ectopic pregnancy, head and neck tumors, trophoblastic and choriocarcinoma tumors, breast, lung, and bladder neoplasms, fungoid mycosis, osteosarcoma, Langerhans cell histiocytosis, Hodgkin's lymphoma, various unicellular lymphomas, graft versus host disease, acute myeloblastic leukemia, and ALL [2][3][4] .…”

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confidence: 99%

Methotrexate, can we do without it?

González-Llano¹,

Briones-Ortegon²,

Colunga‐Pedraza³

et al. 2020

RMU

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Recomendaciones del Grupo Español de Trabajo de Enfermedad de Crohn y Colitis Ulcerosa (GETECCU) sobre el uso de metotrexato en la enfermedad inflamatoria intestinal

Cited by 19 publications

References 76 publications

Noninvasive assessment of liver fibrosis in Crohn’s disease patients exposed to methotrexate

Noninvasive assessment of liver fibrosis in Crohn’s disease patients exposed to methotrexate

Genetic biomarkers of methotrexate response and safety in Crohn's disease: Data from the Spanish ENEIDA registry

Methotrexate, can we do without it?

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