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

@article{barros2026methotrexate,
  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}},
  author = {Barbara de Barros and Farha Sultana and Neeta Maximus and Vivek V. Pai and Anju Wakade and Bhagyashree Bhame and Bishwanath Acharya and Abdulnaser Hamza and Alemtsehay Getachew and Medhi Denisa Alinda and M. Yulianto Listiawan and Shimelis N. Doni and Deanna A. Hagge and Indra Napit and Mahesh Shah and Joydeepa Darlong and Peter Nicholls and Bernd Genser and Saba M. Lambert and Diana N. J. Lockwood and Stephen L. Walker and on behalf of the Erythema Nodosum Leprosum International STudy (ENLIST) Group},
  journal = {PLOS Neglected Tropical Diseases},
  year = {2026},
  month = sep,
  doi = {10.1371/journal.pntd.0014739},
  url = {https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0014739},
  note = {CC BY 4.0},
}

TY  - JOUR
TI  - 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
AU  - Barbara de Barros
AU  - Farha Sultana
AU  - Neeta Maximus
AU  - Vivek V. Pai
AU  - Anju Wakade
AU  - Bhagyashree Bhame
AU  - Bishwanath Acharya
AU  - Abdulnaser Hamza
AU  - Alemtsehay Getachew
AU  - Medhi Denisa Alinda
AU  - M. Yulianto Listiawan
AU  - Shimelis N. Doni
AU  - Deanna A. Hagge
AU  - Indra Napit
AU  - Mahesh Shah
AU  - Joydeepa Darlong
AU  - Peter Nicholls
AU  - Bernd Genser
AU  - Saba M. Lambert
AU  - Diana N. J. Lockwood
AU  - Stephen L. Walker
AU  - on behalf of the Erythema Nodosum Leprosum International STudy (ENLIST) Group
PY  - 2026
DA  - 2026/09/30
JO  - PLOS Neglected Tropical Diseases
DO  - 10.1371/journal.pntd.0014739
UR  - https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0014739
AB  - 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?:
SN  - 1935-2735
ER  -