{
  "abstract": "Background: 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. Methods and findings: 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 18–60 years with severe ENL were randomised to receive oral methotrexate (15mg, increased to 20mg in participants weighing ≥ 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 0.62–1.54). By 48 weeks, 102/137 (74.5%) experienced an ENL flare; adjusted HR 0.95 (95% CI 0.62–1.43). 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). Conclusions: 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. Trial Registration: ClinicalTrials.gov NCT03775460 registered on 29th November 2018. Why was this study done?: What did the researchers do and find?: What do these findings mean?:",
  "abstract_shown": true,
  "affiliations": [
    "Department of Clinical Research, Faculty of Infectious & Tropical Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom",
    "The Leprosy Mission Trust India, New Delhi, India",
    "Bombay Leprosy Project, Mumbai, India",
    "Anandaban Hospital, The Leprosy Mission Nepal, Kathmandu, Nepal",
    "Department of Dermatology, ALERT Comprehensive Specialized Hospital, Addis Ababa, Ethiopia",
    "Department of Dermatology, Venereology & Aesthetic, Faculty of Medicine, Universitas Airlangga, Dr. Soetomo General Academic Hospital, Surabaya, Indonesia",
    "Zero Leprosy Pathfinder Consulting, Baton Rouge, Louisiana, United States of America",
    "ENLIST statistician",
    "High5Data Ltd, Heidelberg, Germany",
    "Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany"
  ],
  "article_type": "Research Article",
  "arxiv": null,
  "author_total": 22,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Barbara de Barros"
    },
    {
      "affs": [
        1
      ],
      "name": "Farha Sultana"
    },
    {
      "affs": [
        2
      ],
      "name": "Neeta Maximus"
    },
    {
      "affs": [
        3
      ],
      "name": "Vivek V. Pai"
    },
    {
      "affs": [
        4
      ],
      "name": "Anju Wakade"
    },
    {
      "affs": [
        5
      ],
      "name": "Bhagyashree Bhame"
    },
    {
      "affs": [
        6
      ],
      "name": "Bishwanath Acharya"
    },
    {
      "affs": [
        7
      ],
      "name": "Abdulnaser Hamza"
    },
    {
      "affs": [
        8
      ],
      "name": "Alemtsehay Getachew"
    },
    {
      "affs": [
        9
      ],
      "name": "Medhi Denisa Alinda"
    },
    {
      "name": "M. Yulianto Listiawan"
    },
    {
      "name": "Shimelis N. Doni"
    },
    {
      "name": "Deanna A. Hagge"
    },
    {
      "name": "Indra Napit"
    },
    {
      "name": "Mahesh Shah"
    },
    {
      "name": "Joydeepa Darlong"
    },
    {
      "name": "Peter Nicholls"
    },
    {
      "name": "Bernd Genser"
    },
    {
      "name": "Saba M. Lambert"
    },
    {
      "name": "Diana N. J. Lockwood"
    },
    {
      "name": "Stephen L. Walker"
    },
    {
      "name": "on behalf of the Erythema Nodosum Leprosum International STudy (ENLIST) Group"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/4dgnazjj01xag.bib",
  "cited_by": 0,
  "doi": "10.1371/journal.pntd.0014739",
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  "id": "4dgnazjj01xag",
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    "1935-2735"
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  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
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      "openalex",
      "2725|Leprosy Research and Treatment"
    ],
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      "plos",
      "/Biology and life sciences/Immunology/Immune response/Inflammation"
    ],
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  "pmcid": null,
  "pmid": null,
  "published": "2026-09-30",
  "publisher": "Public Library of Science",
  "ris": "https://research.draconitic.com/paper/4dgnazjj01xag.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:37Z",
      "native_id": "10.1371/journal.pntd.0014739",
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  "subjects": [
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  "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—MaPs in ENL",
  "title_text": "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—MaPs in ENL",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:37Z",
  "url": "https://research.draconitic.com/paper/4dgnazjj01xag",
  "venue": "PLOS Neglected Tropical Diseases",
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}