{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:09:06Z","timestamp":1790834946292,"version":"4.1.0"},"reference-count":40,"publisher":"BMJ","issue":"11","license":[{"start":{"date-parts":[[2020,11,17]],"date-time":"2020-11-17T00:00:00Z","timestamp":1605571200000},"content-version":"unspecified","delay-in-days":16,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/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":"crossref","award":["704.16.71"],"award-info":[{"award-number":["704.16.71"]}],"id":[{"id":"10.13039\/501100021734","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2020,10,23]]},"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:sec>\n                  <jats:title>Introduction<\/jats:title>\n                  <jats:p>Erythema nodosum leprosum (ENL) is an immunological complication of leprosy. ENL results in morbidity and disability and if it is not treated can lead to death. The current treatment consists of thalidomide or high doses of oral corticosteroids for prolonged periods. Thalidomide is not available in many leprosy endemic countries. The use of corticosteroids is associated with morbidity and mortality. Identifying treatment regimens that reduce the use of corticosteroids in ENL is essential. Methotrexate (MTX) is used to treat many inflammatory diseases and has been used successfully to treat patients with ENL not controlled by other drugs, including prednisolone and thalidomide. We present the protocol of the \u2018MTX and prednisolone study in ENL\u2019 (MaPs in ENL) a randomised controlled trial (RCT) designed to test the efficacy of MTX in the management of ENL.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and analysis<\/jats:title>\n                  <jats:p>MaPs in ENL is an international multicentre RCT, which will be conducted in leprosy referral centres in Bangladesh, Brazil, Ethiopia, India, Indonesia and Nepal. Patients diagnosed with ENL who consent to participate will be randomly allocated to receive 48 weeks of weekly oral MTX plus 20 weeks of prednisolone or 48 weeks of placebo plus 20 weeks of prednisolone. Participants will be stratified by type of ENL into those with acute ENL and those with chronic and recurrent ENL. The primary objective is to determine whether MTX reduces the requirement for additional prednisolone. Patients\u2019 reported outcome measures will be used to assess the efficacy of MTX. Participants will be closely monitored for adverse events.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Ethics and dissemination<\/jats:title>\n                  <jats:p>Results will be submitted for publication in peer-reviewed journals. Ethical approval was obtained from the Observational\/Interventions Research Ethics Committee of the London School of Hygiene &amp; Tropical Medicine (15762); The Leprosy Mission International Bangladesh Institutional Research Board (in process); AHRI-ALERT Ethical Review Committee, Ethiopia; Ethics Committee of the Managing Committee of the Bombay Leprosy Project; and The Leprosy Mission Trust India Ethics Committee; the Nepal Health and Research Council and Health Research Ethics Committee Dr. Soetomo, Indonesia. This study is registered at <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"www.clinicaltrials.gov\">www.clinicaltrials.gov<\/jats:ext-link>. This is the first RCT of MTX for ENL and will contribute to the evidence for the management of ENL.<\/jats:p>\n                  <jats:p>Trial registration number<\/jats:p>\n                  <jats:p>NCT 03775460.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/bmjopen-2020-037700","type":"journal-article","created":{"date-parts":[[2020,11,17]],"date-time":"2020-11-17T16:43:09Z","timestamp":1605631389000},"page":"e037700","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":19,"title":["Methotrexate and prednisolone study in erythema nodosum leprosum (MaPs in ENL) protocol: a double-blind randomised clinical trial"],"prefix":"10.1136","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5382-8165","authenticated-orcid":false,"given":"Barbara","family":"de Barros","sequence":"first","affiliation":[{"name":"Clinical Research Department, London School of Hygiene & Tropical Medicine, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4376-5495","authenticated-orcid":false,"given":"Saba M","family":"Lambert","sequence":"additional","affiliation":[{"name":"Clinical Research Department, London School of Hygiene & Tropical Medicine, London, UK"},{"name":"Clinical Research Department, ALERT Center, Addis Ababa, London, Ethiopia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahesh","family":"Shah","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Mycobacterial Research Laboratories, The Leprosy Mission Nepal, Anandaban Hospital, Kathmandu, Nepal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivek V","family":"Pai","sequence":"additional","affiliation":[{"name":"Bombay Leprosy Project, Mumbai, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joydeepa","family":"Darlong","sequence":"additional","affiliation":[{"name":"The Leprosy Mission Trust India, New Delhi, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin Jewel","family":"Rozario","sequence":"additional","affiliation":[{"name":"DBLM Hospital, The Leprosy Mission International Bangladesh, Nilphamari, Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Medhi Denisa","family":"Alinda","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Venereology, Faculty of Medicine Universitas Airlangga, Dr Soetomo General Hospital, Surabaya, Jawa Timur, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna M","family":"Sales","sequence":"additional","affiliation":[{"name":"Leprosy Laboratory, Instituto Oswaldo Cruz, Rio de Janeiro, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shimelis","family":"Doni","sequence":"additional","affiliation":[{"name":"Clinical Research Department, ALERT Center, Addis Ababa, London, Ethiopia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deanna A","family":"Hagge","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Mycobacterial Research Laboratories, The Leprosy Mission Nepal, Anandaban Hospital, Kathmandu, Nepal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dilip","family":"Shrestha","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Mycobacterial Research Laboratories, The Leprosy Mission Nepal, Anandaban Hospital, Kathmandu, Nepal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Yulianto","family":"Listiawan","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Venereology, Faculty of Medicine Universitas Airlangga, Dr Soetomo General Hospital, Surabaya, Jawa Timur, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abeba M","family":"Yitaye","sequence":"additional","affiliation":[{"name":"Clinical Research Department, ALERT Center, Addis Ababa, London, Ethiopia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose A C","family":"Nery","sequence":"additional","affiliation":[{"name":"Leprosy Laboratory, Instituto Oswaldo Cruz, Rio de Janeiro, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kapil D","family":"Neupane","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Mycobacterial Research Laboratories, The Leprosy Mission Nepal, Anandaban Hospital, Kathmandu, Nepal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivianne L A","family":"Dias","sequence":"additional","affiliation":[{"name":"Leprosy Laboratory, Instituto Oswaldo Cruz, Rio de Janeiro, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. Ruth","family":"Butlin","sequence":"additional","affiliation":[{"name":"DBLM Hospital, The Leprosy Mission International Bangladesh, Nilphamari, Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter G","family":"Nicholls","sequence":"additional","affiliation":[{"name":"Clinical Research Department, London School of Hygiene & Tropical Medicine, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Lockwood","sequence":"additional","affiliation":[{"name":"Clinical Research Department, London School of Hygiene & Tropical Medicine, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2034-8376","authenticated-orcid":false,"given":"Stephen L","family":"Walker","sequence":"additional","affiliation":[{"name":"Clinical Research Department, London School of Hygiene & Tropical Medicine, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2020,11,17]]},"reference":[{"key":"2025101810093774000_10.11.e037700.1","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.2006.74.868"},{"key":"2025101810093774000_10.11.e037700.2","doi-asserted-by":"publisher","DOI":"10.1489\/1544-581X(2004)072<0125:ECOLRY>2.0.CO;2"},{"key":"2025101810093774000_10.11.e037700.3","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0002690"},{"key":"2025101810093774000_10.11.e037700.4","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0004065"},{"key":"2025101810093774000_10.11.e037700.5","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0003431"},{"key":"2025101810093774000_10.11.e037700.6","first-page":"79","article-title":"Pathology of eye in leprosy. In: Indian Journal of Leprosy","volume":"70","author":"Job","year":"1998","journal-title":"Vol"},{"key":"2025101810093774000_10.11.e037700.7","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.00233"},{"key":"2025101810093774000_10.11.e037700.8","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-3083.1999.00622.x"},{"key":"2025101810093774000_10.11.e037700.9","first-page":"623","article-title":"Differences in predominant T cell phenotypes and distribution pattern in reactional lesions of tuberculoid and lepromatous leprosy","volume":"55","author":"Narayanan","year":"1984","journal-title":"Clin Exp Immunol"},{"key":"2025101810093774000_10.11.e037700.10","first-page":"103","article-title":"Serum levels of tumour necrosis factor-alpha and interleukin-1 beta during leprosy reactional states","volume":"84","author":"Sarno","year":"1991","journal-title":"Clin Exp Immunol"},{"key":"2025101810093774000_10.11.e037700.11","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":"Walker","year":"2007","journal-title":"Lepr Rev"},{"key":"2025101810093774000_10.11.e037700.12","doi-asserted-by":"crossref","first-page":"221","DOI":"10.47276\/lr.87.2.221","article-title":"The use of steroids and thalidomide in the management of erythema nodosum leprosum; 17 years at the hospital for tropical diseases, London","volume":"87","author":"Nabarro","year":"2016","journal-title":"Lepr Rev"},{"key":"2025101810093774000_10.11.e037700.13","doi-asserted-by":"crossref","first-page":"142","DOI":"10.47276\/lr.90.2.142","article-title":"A systematic review of adverse drug reactions associated with thalidomide in the treatment of erythema nodosum leprosum","volume":"90","author":"Mahmoud","year":"2019","journal-title":"Lepr Rev"},{"key":"2025101810093774000_10.11.e037700.14","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":"Van Veen","year":"2009","journal-title":"Lepr Rev"},{"key":"2025101810093774000_10.11.e037700.15","first-page":"233","article-title":"Pulsed corticosteroid therapy in patients with chronic recurrent ENL: a pilot study","volume":"74","author":"Girdhar","year":"2002","journal-title":"Indian J Lepr"},{"key":"2025101810093774000_10.11.e037700.16","doi-asserted-by":"crossref","first-page":"518","DOI":"10.4269\/ajtmh.2005.72.518","article-title":"A randomized, double-blind, double-dummy, controlled dose comparison of thalidomide for treatment of erythema nodosum leprosum","volume":"72","author":"Villahermosa","year":"2005","journal-title":"Am J Trop Med Hyg"},{"key":"2025101810093774000_10.11.e037700.17","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1590\/S0100-879X2007000200011","article-title":"Double-Blind trial of the efficacy of pentoxifylline vs thalidomide for the treatment of type II reaction in leprosy","volume":"40","author":"Sales","year":"2007","journal-title":"Braz J Med Biol Res"},{"key":"2025101810093774000_10.11.e037700.18","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":"Kaur","year":"2009","journal-title":"Australas J Dermatol"},{"key":"2025101810093774000_10.11.e037700.19","doi-asserted-by":"publisher","DOI":"10.1111\/ijd.12793"},{"key":"2025101810093774000_10.11.e037700.20","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":"Lambert","year":"2016","journal-title":"PLoS Negl Trop Dis"},{"key":"2025101810093774000_10.11.e037700.21","first-page":"29","article-title":"Comparative efficacy of four treatment regimens in type 2 leprosy reactions (prednisolone alone, thalidomide alone, prednisolone plus thalidomide and prednisolone plus clofazimine)","volume":"88","author":"Kar","year":"2016","journal-title":"Indian J Lepr"},{"key":"2025101810093774000_10.11.e037700.22","doi-asserted-by":"crossref","first-page":"208","DOI":"10.47276\/lr.88.2.208","article-title":"A prospective randomised, double-blind, placebo controlled trial on the effect of extended clofazimine on erythema nodosum leprosum (ENL) in multibacillary (MB) leprosy","volume":"88","author":"Maghanoy","year":"2017","journal-title":"Lepr Rev"},{"key":"2025101810093774000_10.11.e037700.23","first-page":"473","article-title":"Methotrexate in rheumatoid arthritis","volume":"58","author":"Swierkot","year":"2006","journal-title":"Pharmacol Reports"},{"key":"2025101810093774000_10.11.e037700.24","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1111\/bjd.14816","article-title":"British association of dermatologists' guidelines for the safe and effective prescribing of methotrexate for skin disease 2016","volume":"175","author":"Warren","year":"2016","journal-title":"Br J Dermatol"},{"key":"2025101810093774000_10.11.e037700.25","doi-asserted-by":"crossref","unstructured":"Gubner R . Effect of \u201caminopterin\u201d on epithelial tissues. A M A Arch Dermatology Syphilol 1951.","DOI":"10.1001\/archderm.1951.01570120023004"},{"key":"2025101810093774000_10.11.e037700.26","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2013.10.029"},{"key":"2025101810093774000_10.11.e037700.27","unstructured":"WHO . World Health organization model list of essential medicines. Who\/mvp\/emp\/iau 2019;6."},{"key":"2025101810093774000_10.11.e037700.28","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":"2025101810093774000_10.11.e037700.29","first-page":"105","article-title":"Using methotrexate to treat patients with ENL unresponsive to steroids and clofazimine: a report on 9 patients","volume":"84","author":"Hossain","year":"2013","journal-title":"Lepr Rev"},{"key":"2025101810093774000_10.11.e037700.30","doi-asserted-by":"publisher","DOI":"10.1489\/1544-581X(2004)72<480:MIRE>2.0.CO;2"},{"key":"2025101810093774000_10.11.e037700.31","doi-asserted-by":"crossref","first-page":"379","DOI":"10.47276\/lr.86.4.379","article-title":"Effectiveness of methotrexate in prednisolone and thalidomide resistant cases of type 2 lepra reaction: report on three cases","volume":"86","author":"Rahul","year":"2015","journal-title":"Lepr Rev"},{"key":"2025101810093774000_10.11.e037700.32","doi-asserted-by":"crossref","first-page":"e0005716","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":"Walker","year":"2017","journal-title":"PLoS Negl Trop Dis"},{"key":"2025101810093774000_10.11.e037700.33","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(00)02799-9"},{"key":"2025101810093774000_10.11.e037700.34","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kes001"},{"key":"2025101810093774000_10.11.e037700.35","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/39.7.812"},{"key":"2025101810093774000_10.11.e037700.36","doi-asserted-by":"publisher","DOI":"10.1016\/0190-9622(93)70069-6"},{"key":"2025101810093774000_10.11.e037700.37","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.38107.645926.AE"},{"key":"2025101810093774000_10.11.e037700.38","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)17965-3"},{"key":"2025101810093774000_10.11.e037700.39","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbi.2008.08.010"},{"key":"2025101810093774000_10.11.e037700.40","doi-asserted-by":"publisher","DOI":"10.1080\/10543400802609797"}],"container-title":["BMJ Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjopen-2020-037700","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T17:09:47Z","timestamp":1760807387000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopen.bmj.com\/lookup\/doi\/10.1136\/bmjopen-2020-037700"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11]]},"references-count":40,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2020,11,17]]},"published-print":{"date-parts":[[2020,11]]}},"alternative-id":["10.1136\/bmjopen-2020-037700"],"URL":"https:\/\/doi.org\/10.1136\/bmjopen-2020-037700","relation":{},"ISSN":["2044-6055","2044-6055"],"issn-type":[{"value":"2044-6055","type":"print"},{"value":"2044-6055","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11]]}}}