{"title":"Methotrexate in Still's Disease: An Updated Perspective on Efficacy and Safety.","authors":"Karima Daghor-Abbaci, Oya Koker","doi":"10.1007/s12325-026-03823-w","DOIUrl":null,"url":null,"abstract":"<p><p>The EULAR/PreS and American College of Rheumatology (ACR) guidelines for Still's disease (SD) were recently published with new therapeutic management strategies to achieve therapeutic targets within a specified timeframe. The early use of interleukin (IL)-1 or IL-6 inhibitors associated with short-term corticosteroids is recommended. Methotrexate (MTX) is not recommended as initial monotherapy for the acute systemic phase and should not be considered an alternative to early cytokine-targeted therapy when biologic treatment is available. Nevertheless, observational and real-world studies retain clinical utility of MTX as a corticosteroid-sparing agent with a favorable safety profile particularly in adult patients with residual arthritis and preserved organ function. Beyond its well-known immunomodulatory effects, MTX has been hypothesized to influence IL-1-related inflammatory pathways; however, this hypothesis is extrapolated from other inflammatory diseases, and no SD-specific mechanistic study has directly demonstrated an IL-1-mediated therapeutic effect of MTX. Reported remission rates varied according to the therapeutic regimen and study definition and should therefore be interpreted cautiously. In settings where access to biologic agents is limited, MTX may also represent a pragmatic therapeutic option, although this use reflects healthcare constraints rather than evidence of equivalence to IL-1 or IL-6 inhibition. In children with SD, MTX is mainly used for residual arthritis or as a steroid-sparing agent after control of systemic inflammation. Moreover, combining MTX with biologic agents may provide additional benefit in selected patients with residual arthritis or corticosteroid dependence. This review provides an updated perspective on the efficacy and safety of MTX in SD, with particular emphasis on its complementary role within the current biologic-first therapeutic landscape.</p>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":" ","pages":""},"PeriodicalIF":4.7000,"publicationDate":"2026-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Advances in Therapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s12325-026-03823-w","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 0
Abstract
The EULAR/PreS and American College of Rheumatology (ACR) guidelines for Still's disease (SD) were recently published with new therapeutic management strategies to achieve therapeutic targets within a specified timeframe. The early use of interleukin (IL)-1 or IL-6 inhibitors associated with short-term corticosteroids is recommended. Methotrexate (MTX) is not recommended as initial monotherapy for the acute systemic phase and should not be considered an alternative to early cytokine-targeted therapy when biologic treatment is available. Nevertheless, observational and real-world studies retain clinical utility of MTX as a corticosteroid-sparing agent with a favorable safety profile particularly in adult patients with residual arthritis and preserved organ function. Beyond its well-known immunomodulatory effects, MTX has been hypothesized to influence IL-1-related inflammatory pathways; however, this hypothesis is extrapolated from other inflammatory diseases, and no SD-specific mechanistic study has directly demonstrated an IL-1-mediated therapeutic effect of MTX. Reported remission rates varied according to the therapeutic regimen and study definition and should therefore be interpreted cautiously. In settings where access to biologic agents is limited, MTX may also represent a pragmatic therapeutic option, although this use reflects healthcare constraints rather than evidence of equivalence to IL-1 or IL-6 inhibition. In children with SD, MTX is mainly used for residual arthritis or as a steroid-sparing agent after control of systemic inflammation. Moreover, combining MTX with biologic agents may provide additional benefit in selected patients with residual arthritis or corticosteroid dependence. This review provides an updated perspective on the efficacy and safety of MTX in SD, with particular emphasis on its complementary role within the current biologic-first therapeutic landscape.
期刊介绍：
Advances in Therapy is an international, peer reviewed, rapid-publication (peer review in 2 weeks, published 3–4 weeks from acceptance) journal dedicated to the publication of high-quality clinical (all phases), observational, real-world, and health outcomes research around the discovery, development, and use of therapeutics and interventions (including devices) across all therapeutic areas. Studies relating to diagnostics and diagnosis, pharmacoeconomics, public health, epidemiology, quality of life, and patient care, management, and education are also encouraged.
The journal is of interest to a broad audience of healthcare professionals and publishes original research, reviews, communications and letters. The journal is read by a global audience and receives submissions from all over the world. Advances in Therapy will consider all scientifically sound research be it positive, confirmatory or negative data. Submissions are welcomed whether they relate to an international and/or a country-specific audience, something that is crucially important when researchers are trying to target more specific patient populations. This inclusive approach allows the journal to assist in the dissemination of all scientifically and ethically sound research.
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