ReviewTherapeutic advances in gastroenterology2022
Evidence-based efficacy of methotrexate in adult Crohn's disease in different intestinal and extraintestinal indications.
Review in Therapeutic advances in gastroenterology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 20 citations in OpenAlex.
- The Effectiveness of Medical Therapies for Joint, Skin and Eye Extraintestinal Manifestations in IBD-An Umbrella Review.Alimentary pharmacology & therapeutics · 2025Pooled it
- Oral low-dose methotrexate improves infliximab pharmacokinetics, immunogenicity, and endoscopic outcomes in Crohn's disease: a propensity score-adjusted real-world study.International journal of clinical pharmacy · 2026Article
- Microbial metabolism of methotrexate produces a STAT3 signaling molecule that alleviates gut inflammation.bioRxiv : the preprint server for biology · 2026Article
- Beyond rheumatology: Reconsidering methotrexate for Crohn's disease in the biologic era.World journal of gastroenterology · 2026Article
- Methotrexate in the management of Crohn's disease: A practice survey of gastroenterologists in France.World journal of gastroenterology · 2025Article
- Comprehensive Literature Review Evaluating the Use, Safety, and Efficacy of Subcutaneous Methotrexate in the Treatment of Adult Patients With Moderate-To-Severe Plaque-Type Psoriasis.International journal of dermatology · 2025Review
- Comparison of outcomes and postoperative immunotherapy between patients with non-thymomatous and thymomatous myasthenia gravis following thymectomy.Therapeutic advances in neurological disorders · 2025Article
- Efficacy of Methotrexate and Anti-TNF Combination Therapy in Adults with Refractory Crohn's Disease.Middle East journal of digestive diseases · 2024Article
- Management of Crohn's disease in Taiwan: consensus guideline of the Taiwan Society of Inflammatory Bowel Disease updated in 2023.Intestinal research · 2024Article
- Differences in the risk of clinical failure between thiopurine and methotrexate in bio-naïve patients with Crohn's disease: a Korean nationwide population-based study.Therapeutic advances in gastroenterology · 2024Article
- The Role of Low-Dose Oral Methotrexate in Increasing Anti-TNF Drug Levels and Reducing Immunogenicity in IBD.Journal of clinical medicine · 2023Review
- Effectiveness and tolerability of methotrexate monotherapy in Crohn's disease patients: a multicenter observational study.Therapeutic advances in gastroenterology · 2023Article
- Immunomodulators: still having a role?Gastroenterology report · 2022Review
Corrections and comments
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Authors and funding
10 authors at 1 institution.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Introduction: Methotrexate (MTX) is included in the therapeutic armamentarium of Crohn's disease (CD), although its positioning is currently uncertain in an era in which many effective biological drugs are available. No systematic reviews or meta-analysis have stratified the clinical outcomes of MTX according to the specific clinical scenarios of its use. Methods: Medline, PubMed and Scopus were used to extract eligible studies, from database inception to May 2021. A total of 163 studies were included. A systematic review was performed by stratifying the outcomes of MTX according to formulation, clinical indication and criteria of efficacy. Results: The use of MTX is supported by randomized clinical trials only in steroid-dependent CD, with similar outcomes to thiopurines. The use of MTX in patients with steroid-refractoriness, failure of thiopurines or in combination with biologics is not supported by high levels of evidence. Combination therapy with biologics can optimize the immunogenic profile of the biological drug, but the impact on long-term clinical outcomes is described only in small series with anti-TNFα. Other off-label uses, such as fistulizing disease, mucosal healing, postoperative prevention and extraintestinal manifestations, are described in small uncontrolled series. The best performance in most indications was shown by parenteral MTX, favouring higher doses (25 mg/week) in the induction phase. Discussion: Evidence from high-quality studies in favour of MTX is scarce and limited to the steroid-dependent disease, in which other drugs are the leading players today. Many limitations on study design have been found, such as the prevalence of retrospective underpowered studies and the lack of stratification of outcomes according to specific types of patients and formulations of MTX. Conclusion: MTX is a valid option as steroid-sparing agent in steroid-dependent CD. Numerous other clinical scenarios require well-designed clinical studies in terms of patient profile, drug formulation and dosage, and criteria of efficacy.
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