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oai:figshare.com:article/34036278 2026-09-30T17:47:38Z category_7 category_8 category_12 category_13 category_14 category_19 category_39 category_46 category_61 category_64 category_132 category_134 category_135 portal_5 item_type_6 month_year_09_2026

Adverse Events tables. Barbara de Barros (12867558) Farha Sultana (24506948) Neeta Maximus (24506963) Vivek V. Pai (24506954) Anju Wakade (24506957) Bhagyashree Bhame (24506960) Bishwanath Acharya (24506951) Abdulnaser Hamza (24506942) Alemtsehay Getachew (24506945) Medhi Denisa Alinda (12867555) M. Yulianto Listiawan (24506966) Shimelis N. Doni (24506969) Deanna A. Hagge (9384569) Indra Napit (19683872) Mahesh Shah (793725) Joydeepa Darlong (683948) Peter Nicholls (155649) Bernd Genser (747128) Saba M. Lambert (24506972) Diana N. J. Lockwood (9584958) Stephen L. Walker (7879070) Medicine Microbiology Cell Biology Genetics Molecular Biology Pharmacology Ecology Immunology Developmental Biology Cancer Infectious Diseases Virology Computational Biology life improved substantially generally well tolerated affordable immunomodulatory agent adjusted hazard ratio 5 %) experienced severe inflammatory complication 62 &# 8211 differential treatment effect controlled trial conducted receive oral methotrexate week prednisolone regimen enl subsequent flares secondary outcomes related quality primary outcome participants received june 2024 january 2023 identical 20 flare frequency first flare ci 0 adverse effects 60 years 60 weeks 60 kg 54 ). 48 weeks 43 ). 40mg daily 231 individuals <div> BackgroundErythema 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 findingsWe 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). ConclusionsOral 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 RegistrationClinicalTrials.gov <a href="https://clinicaltrials.gov/ct2/show/NCT03775460" target="_blank">NCT03775460</a> registered on 29th November 2018.</div> 2026-09-30T17:54:41Z Text Journal contribution 10.1371/journal.pntd.0014739.s003 https://figshare.com/articles/journal_contribution/_p_Adverse_Events_tables_p_/34036278 CC BY 4.0