{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T18:55:57Z","timestamp":1791485757797,"version":"4.3.4"},"update-to":[{"DOI":"10.1371\/journal.pntd.0014739","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:00:00Z","timestamp":1791417600000}}],"reference-count":54,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Hospital and Homes of St. Giles","award":["ITCRZM25"],"award-info":[{"award-number":["ITCRZM25"]}]},{"DOI":"10.13039\/501100021734","name":"Leprosy Research Initiative","doi-asserted-by":"publisher","award":["704.16.71"],"award-info":[{"award-number":["704.16.71"]}],"id":[{"id":"10.13039\/501100021734","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Erythema nodosum leprosum (ENL) is a severe inflammatory complication of leprosy that often requires prolonged corticosteroid therapy which is associated with adverse effects. Methotrexate is an affordable immunomodulatory agent with limited evidence for its use in ENL treatment. We evaluated whether weekly oral methotrexate in addition to prednisolone reduces the need for additional prednisolone in adults with severe ENL.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods and findings<\/jats:title>\n                    <jats:p>We performed an international, multicentre, double-blind, randomised, placebo-controlled trial conducted at five leprosy referral centres in Ethiopia, India, Indonesia, and Nepal. Adults aged 18\u201360 years with severe ENL were randomised to receive oral methotrexate (15mg, increased to 20mg in participants weighing \u2265 60 kg) for 48 weeks and prednisolone, or matching placebo and prednisolone. All participants received an identical 20-week prednisolone regimen, starting at 40mg daily, and were followed for 60 weeks. The primary outcome was time to first ENL flare requiring additional prednisolone, assessed over 24 and 48 weeks. Between January 2023 and June 2024, 231 individuals were screened and 137 were randomised (68 methotrexate and prednisolone; 69 placebo and prednisolone). By 24 weeks, 85\/137 (62.0%) participants experienced an ENL flare requiring additional prednisolone; the adjusted hazard ratio (HR) for methotrexate versus placebo was 0.98 (95% CI 0.62\u20131.54). By 48 weeks, 102\/137 (74.5%) experienced an ENL flare; adjusted HR 0.95 (95% CI 0.62\u20131.43). Secondary outcomes were similar: methotrexate did not reduce ENL severity at first flare, flare frequency, or severity of subsequent flares. Health-related quality of life improved substantially in both groups with no evidence of a differential treatment effect. Methotrexate was generally well tolerated. The trial was registered at ClinicalTrials.gov (NCT03775460).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Oral methotrexate added to prednisolone did not reduce the requirement for additional prednisolone or delay ENL flares compared to placebo and prednisolone, and our study does not support the use of methotrexate for severe ENL.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec202\">\n                    <jats:title>Trial Registration<\/jats:title>\n                    <jats:p>\n                      ClinicalTrials.gov\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03775460\" xlink:type=\"simple\">NCT03775460<\/jats:ext-link>\n                      registered on 29th November 2018.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pntd.0014739","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T17:47:21Z","timestamp":1790790441000},"page":"e0014739","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Methotrexate and Prednisolone compared to placebo and prednisolone in the treatment of severe Erythema Nodosum Leprosum: An international multicentre, double-blind randomised controlled clinical trial\u2014MaPs in ENL"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5382-8165","authenticated-orcid":true,"given":"Barbara","family":"de Barros","sequence":"first","affiliation":[{"name":"London School of Hygiene & Tropical Medicine","place":["London, United Kingdom"],"department":["Department of Clinical Research, Faculty of Infectious & Tropical Diseases"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farha","family":"Sultana","sequence":"additional","affiliation":[{"name":"The Leprosy Mission Trust India","place":["New Delhi, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neeta","family":"Maximus","sequence":"additional","affiliation":[{"name":"The Leprosy Mission Trust India","place":["New Delhi, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivek V.","family":"Pai","sequence":"additional","affiliation":[{"name":"Bombay Leprosy Project","place":["Mumbai, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anju","family":"Wakade","sequence":"additional","affiliation":[{"name":"Bombay Leprosy Project","place":["Mumbai, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhagyashree","family":"Bhame","sequence":"additional","affiliation":[{"name":"Bombay Leprosy Project","place":["Mumbai, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bishwanath","family":"Acharya","sequence":"additional","affiliation":[{"name":"Anandaban Hospital, The Leprosy Mission Nepal","place":["Kathmandu, Nepal"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdulnaser","family":"Hamza","sequence":"additional","affiliation":[{"name":"ALERT Comprehensive Specialized Hospital","place":["Addis Ababa, Ethiopia"],"department":["Department of Dermatology"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alemtsehay","family":"Getachew","sequence":"additional","affiliation":[{"name":"ALERT Comprehensive Specialized Hospital","place":["Addis Ababa, Ethiopia"],"department":["Department of Dermatology"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Medhi Denisa","family":"Alinda","sequence":"additional","affiliation":[{"name":"Universitas Airlangga, Dr. Soetomo General Academic Hospital","place":["Surabaya, Indonesia"],"department":["Department of Dermatology, Venereology & Aesthetic, Faculty of Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Yulianto","family":"Listiawan","sequence":"additional","affiliation":[{"name":"Universitas Airlangga, Dr. Soetomo General Academic Hospital","place":["Surabaya, Indonesia"],"department":["Department of Dermatology, Venereology & Aesthetic, Faculty of Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shimelis N.","family":"Doni","sequence":"additional","affiliation":[{"name":"ALERT Comprehensive Specialized Hospital","place":["Addis Ababa, Ethiopia"],"department":["Department of Dermatology"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deanna A.","family":"Hagge","sequence":"additional","affiliation":[{"name":"Zero Leprosy Pathfinder Consulting","place":["Baton Rouge, Louisiana, United States of America"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Indra","family":"Napit","sequence":"additional","affiliation":[{"name":"Anandaban Hospital, The Leprosy Mission Nepal","place":["Kathmandu, Nepal"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahesh","family":"Shah","sequence":"additional","affiliation":[{"name":"Anandaban Hospital, The Leprosy Mission Nepal","place":["Kathmandu, Nepal"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joydeepa","family":"Darlong","sequence":"additional","affiliation":[{"name":"The Leprosy Mission Trust India","place":["New Delhi, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Nicholls","sequence":"additional","affiliation":[{"name":"ENLIST statistician"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernd","family":"Genser","sequence":"additional","affiliation":[{"name":"High5Data Ltd","place":["Heidelberg, Germany"]},{"name":"University of Heidelberg","place":["Mannheim, Germany"],"department":["Medical Faculty Mannheim"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saba M.","family":"Lambert","sequence":"additional","affiliation":[{"name":"London School of Hygiene & Tropical Medicine","place":["London, United Kingdom"],"department":["Department of Clinical Research, Faculty of Infectious & Tropical Diseases"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana N. J.","family":"Lockwood","sequence":"additional","affiliation":[{"name":"London School of Hygiene & Tropical Medicine","place":["London, United Kingdom"],"department":["Department of Clinical Research, Faculty of Infectious & Tropical Diseases"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen L.","family":"Walker","sequence":"additional","affiliation":[{"name":"London School of Hygiene & Tropical Medicine","place":["London, United Kingdom"],"department":["Department of Clinical Research, Faculty of Infectious & Tropical Diseases"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"on behalf of the Erythema Nodosum Leprosum International STudy (ENLIST) Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,9,30]]},"reference":[{"key":"pntd.0014739.ref001","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1038\/s41572-024-00575-1","article-title":"Leprosy","volume":"10","author":"ML Grijsen","year":"2024","journal-title":"Nat Rev Dis Primer"},{"key":"pntd.0014739.ref002","first-page":"365","article-title":"Global leprosy (Hansen disease) update, 2024: Beyond zero cases - what elimination of leprosy really means","volume":"100","author":"World Health Organization.","year":"2025","journal-title":"Wkly Epidemiol Rec"},{"key":"pntd.0014739.ref003","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1489\/1544-581X(2004)072<0125:ECOLRY>2.0.CO;2","article-title":"Epidemiological characteristics of leprosy reactions: 15 years experience from North India","volume":"72","author":"B Kumar","year":"2004","journal-title":"Int J Lepr Other Mycobact Dis"},{"issue":"7","key":"pntd.0014739.ref004","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0005725","article-title":"Uniform multidrug therapy for leprosy patients in Brazil (U-MDT\/CT-BR): Results of an open label, randomized and controlled clinical trial, among multibacillary patients","volume":"11","author":"GO Penna","year":"2017","journal-title":"PLoS Negl Trop Dis"},{"key":"pntd.0014739.ref005","doi-asserted-by":"crossref","first-page":"321","DOI":"10.47276\/lr.89.3.321","article-title":"The incidence of erythema nodosum leprosum in India: a retrospective follow-up of the INFIR cohort","volume":"89","author":"SL Walker","year":"2018","journal-title":"Lepr Rev"},{"issue":"5","key":"pntd.0014739.ref006","doi-asserted-by":"crossref","first-page":"868","DOI":"10.4269\/ajtmh.2006.74.868","article-title":"Clinical course of erythema nodosum leprosum: An 11-year cohort study in Hyderabad, India","volume":"74","author":"L Pocaterra","year":"2006","journal-title":"Am J Trop Med Hyg"},{"issue":"10","key":"pntd.0014739.ref007","article-title":"A systematic review on the epidemiological data of erythema nodosum leprosum, a type 2 leprosy reaction","volume":"7","author":"CGN Voorend","year":"2013","journal-title":"PLoS Negl Trop Dis"},{"issue":"9","key":"pntd.0014739.ref008","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0004065","article-title":"ENLIST 1: An International multi-centre cross-sectional study of the clinical features of erythema nodosum leprosum","volume":"9","author":"SL Walker","year":"2015","journal-title":"PLoS Negl Trop Dis"},{"key":"pntd.0014739.ref009","doi-asserted-by":"crossref","first-page":"488","DOI":"10.47276\/lr.88.4.488","article-title":"Health-related quality of life amongst people affected by erythema nodosum leprosum in Bangladesh: A cross sectional study","volume":"88","author":"B Bowers","year":"2017","journal-title":"Lepr Rev"},{"key":"pntd.0014739.ref010","doi-asserted-by":"crossref","first-page":"100","DOI":"10.47276\/lr.91.1.100","article-title":"Health-related quality of life associated with erythema nodosum leprosum in Purulia, West Bengal, India","volume":"91","author":"J Darlong","year":"2020","journal-title":"Lepr Rev"},{"key":"pntd.0014739.ref011","doi-asserted-by":"crossref","first-page":"499","DOI":"10.47276\/lr.88.4.499","article-title":"The impact of erythema nodosum leprosum on health related quality of life in Rio de Janeiro","volume":"88","author":"AM Sales","year":"2017","journal-title":"Lepr Rev"},{"issue":"1","key":"pntd.0014739.ref012","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0003431","article-title":"Household costs of leprosy reactions (ENL) in rural India","volume":"9","author":"DJ Chandler","year":"2015","journal-title":"PLoS Negl Trop Dis"},{"key":"pntd.0014739.ref013","doi-asserted-by":"crossref","first-page":"233","DOI":"10.3389\/fimmu.2017.00233","article-title":"A systematic review of immunological studies of erythema nodosum leprosum","volume":"8","author":"A Polycarpou","year":"2017","journal-title":"Front Immunol"},{"issue":"7","key":"pntd.0014739.ref014","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0010641","article-title":"Regulatory T cells in erythema nodosum leprosum maintain anti-inflammatory function","volume":"16","author":"E Negera","year":"2022","journal-title":"PLoS Negl Trop Dis"},{"key":"pntd.0014739.ref015","doi-asserted-by":"crossref","first-page":"189","DOI":"10.3389\/fimmu.2018.00189","article-title":"The effects of prednisolone treatment on cytokine expression in patients with erythema nodosum leprosum reactions","volume":"9","author":"E Negera","year":"2018","journal-title":"Front Immunol"},{"issue":"10","key":"pntd.0014739.ref016","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0006011","article-title":"Clinico-pathological features of erythema nodosum leprosum: A case-control study at ALERT hospital, Ethiopia","volume":"11","author":"E Negera","year":"2017","journal-title":"PLoS Negl Trop Dis"},{"key":"pntd.0014739.ref017","author":"Regional Office for South-East Asia.","year":"2017"},{"issue":"3","key":"pntd.0014739.ref018","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0002690","article-title":"The mortality associated with erythema nodosum leprosum in Ethiopia: A retrospective hospital-based study","volume":"8","author":"SL Walker","year":"2014","journal-title":"PLoS Negl Trop Dis"},{"key":"pntd.0014739.ref019","article-title":"A systematic review of adverse effects associated with systemic corticosteroids in the management of leprosy","author":"AI Lun","journal-title":"PLoS Negl Trop Dis"},{"key":"pntd.0014739.ref020","doi-asserted-by":"crossref","first-page":"68","DOI":"10.47276\/lr.90.1.68","article-title":"Retrospective study of the morbidity associated with erythema nodosum leprosum in Brazilian leprosy patients","author":"D Neves","year":"2019","journal-title":"Lepr Rev"},{"issue":"3","key":"pntd.0014739.ref021","doi-asserted-by":"crossref","first-page":"254","DOI":"10.47276\/lr.79.3.254","article-title":"Erythema nodosum leprosum in Nepal: A retrospective study of clinical features and response to treatment with prednisolone or thalidomide","volume":"79","author":"M Feuth","year":"2008","journal-title":"Lepr Rev"},{"issue":"10","key":"pntd.0014739.ref022","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0008678","article-title":"Thalidomide in the treatment of erythema nodosum leprosum (ENL) in an outpatient setting: A five-year retrospective analysis from a leprosy referral centre in India","volume":"14","author":"B Upputuri","year":"2020","journal-title":"PLoS Negl Trop Dis"},{"issue":"3","key":"pntd.0014739.ref023","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1111\/j.1440-0960.2009.00534.x","article-title":"Comparative efficacy of thalidomide and prednisolone in the treatment of moderate to severe erythema nodosum leprosum: A randomized study","volume":"50","author":"I Kaur","year":"2009","journal-title":"Australas J Dermatol"},{"issue":"8","key":"pntd.0014739.ref024","doi-asserted-by":"crossref","first-page":"1368","DOI":"10.1093\/rheumatology\/kes001","article-title":"A randomized placebo-controlled trial of methotrexate in psoriatic arthritis","volume":"51","author":"GH Kingsley","year":"2012","journal-title":"Rheumatology (Oxford)"},{"key":"pntd.0014739.ref025","doi-asserted-by":"crossref","first-page":"113074","DOI":"10.1016\/j.biopha.2022.113074","article-title":"Application and pharmacological mechanism of methotrexate in rheumatoid arthritis","volume":"150","author":"Z Zhao","year":"2022","journal-title":"Biomed Pharmacother"},{"issue":"7","key":"pntd.0014739.ref026","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1002\/acr.24596","article-title":"2021 American College of Rheumatology guideline for the treatment of rheumatoid arthritis","volume":"73","author":"L Fraenkel","year":"2021","journal-title":"Arthritis Care Res (Hoboken)"},{"key":"pntd.0014739.ref027","first-page":"2014","article-title":"Methotrexate in resistant juvenile rheumatoid arthritis","volume":"326","author":"D Classen","year":"1992","journal-title":"N Engl J Med"},{"issue":"1","key":"pntd.0014739.ref028","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1111\/bjd.14816","article-title":"British Association of Dermatologists\u2019 guidelines for the safe and effective prescribing of methotrexate for skin disease 2016","volume":"175","author":"RB Warren","year":"2016","journal-title":"Br J Dermatol"},{"key":"pntd.0014739.ref029","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1097\/JD9.0000000000000133","article-title":"Efficacy and safety of prednisolone monotherapy versus prednisolone plus methotrexate in erythema nodosum leprosum (type 2 lepra reaction)","volume":"3","author":"Z Hasan","year":"2020","journal-title":"Int J Dermatol Venereol"},{"issue":"4","key":"pntd.0014739.ref030","doi-asserted-by":"crossref","first-page":"396","DOI":"10.47276\/lr.83.4.396","article-title":"International workshop on erythema nodosum leprosum (ENL) - consensus report; the formation of ENLIST, the ENL International STudy group","volume":"83","author":"SL Walker","year":"2012","journal-title":"Lep Rev"},{"issue":"11","key":"pntd.0014739.ref031","doi-asserted-by":"crossref","DOI":"10.1136\/bmjopen-2020-037700","article-title":"Methotrexate and prednisolone study in erythema nodosum leprosum (MaPs in ENL) protocol: A double-blind randomised clinical trial","volume":"10","author":"B de Barros","year":"2020","journal-title":"BMJ Open"},{"issue":"7","key":"pntd.0014739.ref032","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0005716","article-title":"A leprosy clinical severity scale for erythema nodosum leprosum: An international, multicentre validation study of the ENLIST ENL Severity Scale","volume":"11","author":"SL Walker","year":"2017","journal-title":"PLoS Negl Trop Dis"},{"key":"pntd.0014739.ref033","article-title":"Dermatology life quality index (DLQI)\u2014a simple practical measure for routine clinical use","author":"AY Finlay","year":"1994","journal-title":"Clin Exp Dermatol"},{"key":"pntd.0014739.ref034","article-title":"SF-36 health survey manual and interpretation guide","author":"JE Ware","year":"1993","journal-title":"N Engl Med Cent"},{"issue":"4","key":"pntd.0014739.ref035","doi-asserted-by":"crossref","first-page":"355","DOI":"10.47276\/lr.80.4.355","article-title":"Interventions for erythema nodosum leprosum. A cochrane review","volume":"80","author":"NHJ Van Veen","year":"2009","journal-title":"Lepr Rev"},{"issue":"11","key":"pntd.0014739.ref036","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1111\/ijd.12793","article-title":"Effectiveness and safety of clofazimine and pentoxifylline in type 2 lepra reaction: A double-blind, randomized, controlled study","volume":"54","author":"K Roy","year":"2015","journal-title":"Int J Dermatol"},{"issue":"2","key":"pntd.0014739.ref037","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0004149","article-title":"Comparison of efficacy and safety of ciclosporin to prednisolone in the treatment of erythema nodosum leprosum: Two randomised, double blind, controlled pilot studies in Ethiopia","volume":"10","author":"SM Lambert","year":"2016","journal-title":"PLoS Negl Trop Dis"},{"key":"pntd.0014739.ref038","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0011238","article-title":"Methotrexate as a corticosteroid-sparing agent in leprosy reactions: A French multicenter retrospective study. (GrIDIST) G d\u2019infectiologie en dermatologie et des infections sexuellement transmissibles, editor","volume":"17","author":"L Jaume","year":"2023","journal-title":"PLoS Negl Trop Dis"},{"issue":"20","key":"pntd.0014739.ref039","doi-asserted-by":"crossref","first-page":"5023","DOI":"10.3390\/ijms20205023","article-title":"Methotrexate an old drug with new tricks","volume":"20","author":"Y Bedoui","year":"2019","journal-title":"Int J Mol Sci"},{"issue":"7","key":"pntd.0014739.ref040","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1056\/NEJMc052955","article-title":"Treatment of recurrent erythema nodosum leprosum with infliximab","volume":"355","author":"WR Faber","year":"2006","journal-title":"N Engl J Med"},{"issue":"2","key":"pntd.0014739.ref041","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.ijmyco.2016.02.002","article-title":"Treatment of severe refractory erythema nodosum leprosum with tumor necrosis factor inhibitor Etanercept","volume":"5","author":"S Chowdhry","year":"2016","journal-title":"Int J Mycobacteriol"},{"issue":"5","key":"pntd.0014739.ref042","doi-asserted-by":"crossref","DOI":"10.1093\/cid\/ciq213","article-title":"Severe refractory erythema nodosum leprosum successfully treated with the tumor necrosis factor inhibitor etanercept","volume":"52","author":"ML Ramien","year":"2011","journal-title":"Clin Infect Dis"},{"issue":"2","key":"pntd.0014739.ref043","doi-asserted-by":"crossref","first-page":"243","DOI":"10.25259\/IJDVL_726_20","article-title":"Can etanercept be an option in management of recurrent steroid-dependent erythema nodosum leprosum? A retrospective study of six patients","volume":"88","author":"MK Sahani","year":"2022","journal-title":"Indian J Dermatol Venereol Leprol"},{"key":"pntd.0014739.ref044","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.4269\/ajtmh.19-0616","article-title":"Biologics in leprosy: A systematic review and case report","volume":"102","author":"AL Cogen","year":"2020","journal-title":"Am J Trop Med Hyg"},{"issue":"9140","key":"pntd.0014739.ref045","doi-asserted-by":"crossref","first-page":"1586","DOI":"10.1016\/S0140-6736(98)02197-7","article-title":"Randomised comparison of thalidomide versus placebo in toxic epidermal necrolysis","volume":"352","author":"P Wolkenstein","year":"1998","journal-title":"Lancet"},{"issue":"3","key":"pntd.0014739.ref046","doi-asserted-by":"crossref","first-page":"197","DOI":"10.47276\/lr.78.3.197","article-title":"The role of thalidomide in the management of erythema nodosum leprosum","volume":"78","author":"SL Walker","year":"2007","journal-title":"Lepr Rev"},{"key":"pntd.0014739.ref047","doi-asserted-by":"crossref","first-page":"186","DOI":"10.47276\/lr.94.3.186","article-title":"Access to thalidomide","volume":"94","author":"RC Butlin","year":"2023","journal-title":"Lepr Rev"},{"issue":"1","key":"pntd.0014739.ref048","doi-asserted-by":"crossref","DOI":"10.1086\/518699","article-title":"Methotrexate treatment for type 1 (reversal) leprosy reactions","volume":"45","author":"G Biosca","year":"2007","journal-title":"Clin Infect Dis"},{"key":"pntd.0014739.ref049","first-page":"252","article-title":"Mycobacteria.","volume-title":"Tropical Dermatology","author":"SK Tyring","year":"2016","edition":"2"},{"issue":"12","key":"pntd.0014739.ref050","article-title":"Cytokine and protein markers of leprosy reactions in skin and nerves: baseline results for the North Indian INFIR cohort","volume":"5","author":"DNJ Lockwood","year":"2011","journal-title":"PLoS Negl Trop Dis"},{"key":"pntd.0014739.ref051","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/s43166-023-00178-w","article-title":"Efficacy and gastrointestinal tolerability of methotrexate in late-onset rheumatoid arthritis patients: A prospective cohort study","volume":"50","author":"ED Bayrak","year":"2023","journal-title":"Egypt Rheumatol Rehabil"},{"issue":"11","key":"pntd.0014739.ref052","doi-asserted-by":"crossref","DOI":"10.1001\/jamanetworkopen.2023.45132","article-title":"Low-dose methotrexate and serious adverse events among older adults with chronic kidney disease","volume":"6","author":"FT Muanda","year":"2023","journal-title":"JAMA Netw Open"},{"issue":"6","key":"pntd.0014739.ref053","doi-asserted-by":"crossref","first-page":"369","DOI":"10.7326\/M19-3369","article-title":"Adverse effects of low-dose methotrexate: A randomized trial","volume":"172","author":"DH Solomon","year":"2020","journal-title":"Ann Intern Med"},{"issue":"10","key":"pntd.0014739.ref054","doi-asserted-by":"crossref","first-page":"3930","DOI":"10.1093\/rheumatology\/keab917","article-title":"Rates and predictors of methotrexate-related adverse events in patients with early rheumatoid arthritis: results from a nationwide UK study","volume":"61","author":"RAMS Co-Investigators","year":"2022","journal-title":"Rheumatology (Oxford)"}],"updated-by":[{"DOI":"10.1371\/journal.pntd.0014739","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:00:00Z","timestamp":1791417600000}}],"container-title":["PLOS Neglected Tropical Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pntd.0014739","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T17:54:47Z","timestamp":1791482087000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pntd.0014739"}},"subtitle":[],"editor":[{"given":"Epco","family":"Hasker","sequence":"first","affiliation":[{"name":"Institute of Tropical Medicine: Instituut voor Tropische Geneeskunde","place":["BELGIUM"]}],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,9,30]]},"references-count":54,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9,30]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pntd.0014739","relation":{},"ISSN":["1935-2735"],"issn-type":[{"value":"1935-2735","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,30]]}}}