{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T17:50:23Z","timestamp":1757613023359,"version":"3.44.0"},"reference-count":66,"publisher":"BMJ","issue":"5","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["Pract Neurol"],"accepted":{"date-parts":[[2024,5,14]]},"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:p>The use of methotrexate in clinical practice has expanded significantly in recent years, as an effective chemotherapeutic agent as well as disease-modifying treatment for conditions such as rheumatoid arthritis, psoriasis and Crohn\u2019s disease. It is also used as a steroid-sparing agent for a range of inflammatory diseases of the central and peripheral nervous systems. Clinical neurologists must, therefore, know how to start and uptitrate methotrexate, its monitoring requirements and its potential toxicities. This review aims first to explore the evidence base for using methotrexate in various neurological diseases and second to discuss important practicalities around its use, ensuring its safe application and appropriate monitoring.<\/jats:p>","DOI":"10.1136\/pn-2024-004156","type":"journal-article","created":{"date-parts":[[2024,5,31]],"date-time":"2024-05-31T19:12:38Z","timestamp":1717182758000},"page":"369-375","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Methotrexate for the neurologist"],"prefix":"10.1136","volume":"24","author":[{"given":"Aaron","family":"Jesuthasan","sequence":"first","affiliation":[{"name":"Department of Neurology, Addenbrooke's Hospital, Cambridge, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aravindhan","family":"Baheerathan","sequence":"additional","affiliation":[{"name":"Department of Neurology, Charing Cross Hospital, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5911-7049","authenticated-orcid":false,"given":"Stephen","family":"Auger","sequence":"additional","affiliation":[{"name":"Department of Neurology, Charing Cross Hospital, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachel","family":"Dorsey","sequence":"additional","affiliation":[{"name":"Department of Neurology, Charing Cross Hospital, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robina","family":"Coker","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Hammersmith Hospital, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nowlan","family":"Selvapatt","sequence":"additional","affiliation":[{"name":"Department of Hepatology, St Mary's Hospital, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stuart","family":"Viegas","sequence":"additional","affiliation":[{"name":"Department of Neurology, Charing Cross Hospital, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2024,5,31]]},"reference":[{"key":"2025090409511172000_24.5.369.1","doi-asserted-by":"crossref","DOI":"10.3390\/ijms20205023","article-title":"Methotrexate an old drug with new tricks","volume":"20","author":"Bedoui","year":"2019","journal-title":"Int J Mol Sci"},{"key":"2025090409511172000_24.5.369.2","unstructured":"Hannoodee M , Mittal M . Methotrexate. StatPearls Treasure Island (FL): StatPearls Publishing; 2022. Available: http:\/\/www.ncbi.nlm.nih.gov\/books\/NBK556114\/"},{"key":"2025090409511172000_24.5.369.3","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-020-0373-9"},{"key":"2025090409511172000_24.5.369.4","doi-asserted-by":"publisher","DOI":"10.1136\/ard.60.8.729"},{"key":"2025090409511172000_24.5.369.5","doi-asserted-by":"publisher","DOI":"10.2133\/dmpk.DMPK-13-RV-119"},{"key":"2025090409511172000_24.5.369.6","doi-asserted-by":"crossref","first-page":"2228","DOI":"10.1111\/bcp.14057","article-title":"Optimising low-dose methotrexate for rheumatoid arthritis\u2014A review","volume":"85","author":"Lucas","year":"2019","journal-title":"Br J Clin Pharmacol"},{"key":"2025090409511172000_24.5.369.7","doi-asserted-by":"publisher","DOI":"10.1172\/JCI112088"},{"key":"2025090409511172000_24.5.369.8","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.1993.tb04158.x"},{"key":"2025090409511172000_24.5.369.9","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780330620"},{"key":"2025090409511172000_24.5.369.10","doi-asserted-by":"crossref","first-page":"67","DOI":"10.2147\/OARRR.S131668","article-title":"Recommendations for optimizing methotrexate treatment for patients with rheumatoid arthritis","volume":"9","author":"Bello","year":"2017","journal-title":"Open Access Rheumatol"},{"key":"2025090409511172000_24.5.369.11","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1042\/BST20190803","article-title":"How does methotrexate work?","volume":"48","author":"Alqarni","year":"2020","journal-title":"Biochem Soc Trans"},{"key":"2025090409511172000_24.5.369.12","doi-asserted-by":"crossref","first-page":"105","DOI":"10.2147\/TCRM.S154745","article-title":"Update on subcutaneous methotrexate for inflammatory arthritis and psoriasis","volume":"14","author":"Vena","year":"2018","journal-title":"Ther Clin Risk Manag"},{"key":"2025090409511172000_24.5.369.13","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keq216"},{"key":"2025090409511172000_24.5.369.14","unstructured":"General medical Council . Prescribing Unlicensed medicines. 2024. Available: https:\/\/www.gmc-uk.org\/professional-standards\/professional-standards-for-doctors\/good-practice-in-prescribing-and-managing-medicines-and-devices\/prescribing-unlicensed-medicines"},{"key":"2025090409511172000_24.5.369.15","unstructured":"GOV.UK . Off-label or Unlicensed use of medicines: Prescribers\u2019 responsibilities. 2024. Available: https:\/\/www.gov.uk\/drug-safety-update\/off-label-or-unlicensed-use-of-medicines-prescribers-responsibilities"},{"key":"2025090409511172000_24.5.369.16","unstructured":"GOV.UK . Methotrexate once-weekly for autoimmune diseases: new measures to reduce risk of fatal overdose due to inadvertent daily instead of weekly dosing. 2024. Available: https:\/\/www.gov.uk\/drug-safety-update\/methotrexate-once-weekly-for-autoimmune-diseases-new-measures-to-reduce-risk-of-fatal-overdose-due-to-inadvertent-daily-instead-of-weekly-dosing"},{"key":"2025090409511172000_24.5.369.17","doi-asserted-by":"publisher","DOI":"10.1136\/dtb.2020.000061"},{"key":"2025090409511172000_24.5.369.18","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keh088"},{"key":"2025090409511172000_24.5.369.19","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1093\/rheumatology\/keab313","article-title":"Effectiveness and tolerability of oral vs subcutaneous methotrexate in patients with rheumatoid arthritis","volume":"61","author":"Heuvelmans","year":"2021","journal-title":"Rheumatology (Oxford)"},{"key":"2025090409511172000_24.5.369.20","unstructured":"NICE . Monitoring of Dmards. 2024. Available: https:\/\/cks.nice.org.uk\/topics\/dmards\/management\/monitoring-of-dmards\/"},{"key":"2025090409511172000_24.5.369.21","unstructured":"NHS England . National shared care protocol: methotrexate (oral and subcutaneous) for patients in adult services (excluding cancer care). 2024. Available: https:\/\/view.officeapps.live.com\/op\/view.aspx?src=https%3A%2F%2Fwww.england.nhs.uk%2Fwp-content%2Fuploads%2F2022%2F07%2FB1621_xvii_methotrexate-oral-and-subcutaneous-for-patients-in-adult-services-excluding-cancer-care.docx&wdOrigin=BROWSELINK"},{"key":"2025090409511172000_24.5.369.22","doi-asserted-by":"publisher","DOI":"10.1136\/pn-2023-003708"},{"key":"2025090409511172000_24.5.369.23","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2022-222155"},{"key":"2025090409511172000_24.5.369.24","doi-asserted-by":"crossref","DOI":"10.1136\/rmdopen-2022-002899","article-title":"Methotrexate in pregnancy: still many unanswered questions","volume":"9","author":"Weber-Schoendorfer","year":"2023","journal-title":"RMD Open"},{"key":"2025090409511172000_24.5.369.25","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1080\/17425255.2017.1230198","article-title":"The toxicity of methotrexate in male fertility and paternal teratogenicity","volume":"13","author":"Gutierrez","year":"2017","journal-title":"Expert Opin Drug Metab Toxicol"},{"key":"2025090409511172000_24.5.369.26","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2020-eular.4835"},{"key":"2025090409511172000_24.5.369.27","doi-asserted-by":"crossref","DOI":"10.1007\/s11926-014-0431-x","article-title":"Vaccinations for rheumatoid arthritis","volume":"16","author":"Perry","year":"2014","journal-title":"Curr Rheumatol Rep"},{"key":"2025090409511172000_24.5.369.28","unstructured":"GOV.UK . Shingles (herpes Zoster): the green book, Chapter 28A. 2024. Available: https:\/\/www.gov.uk\/government\/publications\/shingles-herpes-zoster-the-green-book-chapter-28a"},{"key":"2025090409511172000_24.5.369.29","unstructured":"GOV.UK . Post exposure prophylaxis for Chickenpox and shingles. 2024. Available: https:\/\/www.gov.uk\/government\/publications\/post-exposure-prophylaxis-for-chickenpox-and-shingles"},{"key":"2025090409511172000_24.5.369.30","first-page":"53","article-title":"Methotrexate and trimethoprim-sulfamethoxazole","volume":"60","author":"Cudmore","year":"2014","journal-title":"Can Fam Physician"},{"key":"2025090409511172000_24.5.369.31","unstructured":"Cleveland Clinic . Safety of Trimethoprim-Sulfamethoxazole for Pneumocystis Jirovecii pneumonia prophylaxis in patients taking methotrexate outcomes. 2024. Available: https:\/\/my.clevelandclinic.org\/departments\/dermatology-plastic-surgery\/outcomes\/1072-safety-of-trimethoprim-sulfamethoxazole-for-pneumocystis-jirovecii-pneumonia-prophylaxis-in-patients-taking-methotrexate"},{"key":"2025090409511172000_24.5.369.32","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.100858"},{"key":"2025090409511172000_24.5.369.33","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1002\/pds.4555","article-title":"Concomitant use of low-dose methotrexate and NSAIDs and the risk of serious adverse events among patients with rheumatoid arthritis","volume":"27","author":"Svanstr\u00f6m","year":"2018","journal-title":"Pharmacoepidemiol Drug Saf"},{"key":"2025090409511172000_24.5.369.34","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.1989.00390030137027"},{"key":"2025090409511172000_24.5.369.35","article-title":"Overview of methotrexate toxicity: a comprehensive literature review","volume":"14","author":"Hamed","year":"2022","journal-title":"Cureus"},{"key":"2025090409511172000_24.5.369.36","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1002\/acr2.11187","article-title":"Adverse effects of low-dose methotrexate in a randomized double-blind placebo-controlled trial: adjudicated hematologic and skin cancer outcomes in the cardiovascular inflammation reduction trial","volume":"2","author":"Vanni","year":"2020","journal-title":"ACR Open Rheumatol"},{"key":"2025090409511172000_24.5.369.37","doi-asserted-by":"crossref","first-page":"2286","DOI":"10.1111\/bcp.14641","article-title":"Risk of haematological events and preventive effect of folic acid in methotrexate users with chronic kidney disease and rheumatoid arthritis: analysis of the Japanese adverse drug event report database","volume":"87","author":"Mitsuboshi","year":"2021","journal-title":"Br J Clin Pharmacol"},{"key":"2025090409511172000_24.5.369.38","doi-asserted-by":"crossref","DOI":"10.1136\/rmdopen-2020-001235","article-title":"Risk for infections with glucocorticoids and dmards in patients with rheumatoid arthritis","volume":"7","author":"Riley","year":"2021","journal-title":"RMD Open"},{"key":"2025090409511172000_24.5.369.39","doi-asserted-by":"crossref","first-page":"2168","DOI":"10.1111\/bcp.15687","article-title":"Risk of infection from glucocorticoid and methotrexate interaction in patients with rheumatoid arthritis using biologics: a retrospective cohort study","volume":"89","author":"Ota","year":"2023","journal-title":"Br J Clin Pharmacol"},{"key":"2025090409511172000_24.5.369.40","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kep101"},{"key":"2025090409511172000_24.5.369.41","doi-asserted-by":"crossref","DOI":"10.3390\/jcm8010015","article-title":"Risk of infection with methotrexate therapy in inflammatory diseases: a systematic review and meta-analysis","volume":"8","author":"Ibrahim","year":"2018","journal-title":"J Clin Med"},{"key":"2025090409511172000_24.5.369.42","doi-asserted-by":"crossref","first-page":"4844","DOI":"10.4103\/jfmpc.jfmpc_280_22","article-title":"Methotrexate induced pneumonitis \u2013 A case report and review of literature","volume":"11","author":"Vinay","year":"2022","journal-title":"J Family Med Prim Care"},{"key":"2025090409511172000_24.5.369.43","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1809798"},{"key":"2025090409511172000_24.5.369.44","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.1985.00360110105023"},{"key":"2025090409511172000_24.5.369.45","doi-asserted-by":"crossref","unstructured":"Chikura B , Sathi N , Dawson JK . Methotrexate induced Pneumonitis: A review article. Current Respiratory Medicine Reviews. 12\u201320.","DOI":"10.2174\/157339809787354038"},{"key":"2025090409511172000_24.5.369.46","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-3003.2000.15b25.x"},{"key":"2025090409511172000_24.5.369.47","doi-asserted-by":"crossref","first-page":"1900","DOI":"10.1093\/rheumatology\/kez337","article-title":"Methotrexate and interstitial lung disease: controversies and questions. A narrative review of the literature","volume":"58","author":"Fragoulis","year":"2019","journal-title":"Rheumatology (Oxford)"},{"key":"2025090409511172000_24.5.369.48","doi-asserted-by":"crossref","DOI":"10.1183\/13993003.00337-2020","article-title":"Methotrexate and rheumatoid arthritis associated interstitial lung disease","volume":"57","author":"Juge","year":"2021","journal-title":"Eur Respir J"},{"key":"2025090409511172000_24.5.369.49","doi-asserted-by":"crossref","DOI":"10.1136\/bmjopen-2018-028466","article-title":"Is incident rheumatoid arthritis interstitial lung disease associated with methotrexate treatment? results from a multivariate analysis in the ERAS and ERAN inception cohorts","volume":"9","author":"Kiely","year":"2019","journal-title":"BMJ Open"},{"key":"2025090409511172000_24.5.369.50","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1007\/s00296-020-04773-4","article-title":"Does methotrexate cause progressive fibrotic interstitial lung disease? A systematic review","volume":"41","author":"Dawson","year":"2021","journal-title":"Rheumatol Int"},{"key":"2025090409511172000_24.5.369.51","doi-asserted-by":"crossref","DOI":"10.1093\/omcr\/omy058","article-title":"Abnormal liver function tests in inflammatory arthritis: think beyond the dmards","volume":"2018","author":"Fahmy","year":"2018","journal-title":"Oxf Med Case Reports"},{"key":"2025090409511172000_24.5.369.52","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1016\/j.jhep.2022.12.034","article-title":"Risk of liver fibrosis associated with long-term methotrexate therapy may be overestimated","volume":"78","author":"Atallah","year":"2023","journal-title":"J Hepatol"},{"key":"2025090409511172000_24.5.369.53","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1016\/j.jhep.2023.02.018","article-title":"Methotrexate-induced liver fibrosis: the end of a long-held belief","volume":"78","author":"Di Martino","year":"2023","journal-title":"J Hepatol"},{"key":"2025090409511172000_24.5.369.54","first-page":"605","article-title":"Fibroscan (transient Elastography) for the measurement of liver fibrosis","volume":"8","author":"Afdhal","year":"2012","journal-title":"Gastroenterol Hepatol"},{"key":"2025090409511172000_24.5.369.55","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1111\/j.1445-5994.2012.02755.x","article-title":"Improved survival trend of patients with hepatocellular carcinoma at an Australian tertiary hospital between 1995-2009","volume":"43","author":"Wong","year":"2013","journal-title":"Intern Med J"},{"key":"2025090409511172000_24.5.369.56","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2013.53.0808"},{"key":"2025090409511172000_24.5.369.57","doi-asserted-by":"crossref","first-page":"1644","DOI":"10.1002\/ccr3.1110","article-title":"Methotrexate\u2010Induced leukoencephalopathy presenting as stroke in the emergency department","volume":"5","author":"Cruz-Carreras","year":"2017","journal-title":"Clin Case Rep"},{"key":"2025090409511172000_24.5.369.58","doi-asserted-by":"crossref","DOI":"10.1182\/blood-2021-153241","article-title":"Induced Leukoencephalopathy(LE) and relation of vitamin B12, folate and \/ or homocysteine levels with MTX toxicity: a prospective study","volume":"138","author":"Lahoti","year":"2021","journal-title":"Blood"},{"key":"2025090409511172000_24.5.369.59","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1016\/j.radcr.2022.11.057","article-title":"Recurrence of methotrexate-induced leukoencephalopathy after methotrexate rechallenge: a case report and literature review","volume":"18","author":"AlKawi","year":"2023","journal-title":"Radiol Case Rep"},{"key":"2025090409511172000_24.5.369.60","doi-asserted-by":"crossref","DOI":"10.1007\/s40800-019-0106-7","article-title":"Acute kidney injury following high-dose methotrexate administration in a day care hospital","volume":"6","author":"Misra","year":"2019","journal-title":"Drug Saf Case Rep"},{"key":"2025090409511172000_24.5.369.61","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2015-0164"},{"key":"2025090409511172000_24.5.369.62","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2021050598"},{"key":"2025090409511172000_24.5.369.63","doi-asserted-by":"crossref","first-page":"131","DOI":"10.5414\/CP203604","article-title":"Association between malignancy and methotrexate and biological disease-modifying antirheumatic drugs in patients with rheumatoid arthritis","volume":"58","author":"Inose","year":"2020","journal-title":"Int J Clin Pharmacol Ther"},{"key":"2025090409511172000_24.5.369.64","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1038\/s41416-023-02172-7","article-title":"Use of methotrexate and risk of skin cancer: a nationwide case\u2013control study","volume":"128","author":"Polesie","year":"2023","journal-title":"Br J Cancer"},{"key":"2025090409511172000_24.5.369.65","first-page":"322","article-title":"Lymphoproliferative disorders in rheumatoid arthritis: clinicopathological analysis of 76 cases in relation to methotrexate medication","volume":"34","author":"Hoshida","year":"2007","journal-title":"J Rheumatol"},{"key":"2025090409511172000_24.5.369.66","doi-asserted-by":"crossref","unstructured":"Suzuki M , Matsubayashi S , Sakamoto K , et al . Clinical characteristics of methotrexate associated lymphoproliferative disorders >please type your abstract title in sentence case. Eur Respir J 2021. Available: https:\/\/erj.ersjournals.com\/content\/58\/suppl_65\/PA3296","DOI":"10.1183\/13993003.congress-2021.PA3296"}],"container-title":["Practical Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/pn-2024-004156","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T16:51:27Z","timestamp":1757004687000},"score":1,"resource":{"primary":{"URL":"https:\/\/pn.bmj.com\/lookup\/doi\/10.1136\/pn-2024-004156"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,31]]},"references-count":66,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2024,9,13]]},"published-print":{"date-parts":[[2024,10]]}},"alternative-id":["10.1136\/pn-2024-004156"],"URL":"https:\/\/doi.org\/10.1136\/pn-2024-004156","relation":{},"ISSN":["1474-7758","1474-7766"],"issn-type":[{"type":"print","value":"1474-7758"},{"type":"electronic","value":"1474-7766"}],"subject":[],"published":{"date-parts":[[2024,5,31]]}}}