Corticosteroid-Sparing Strategies For The Management Of Leprosy Reactions: A Systematic Review Of Emerging Therapeutic Approaches

Abstract

Leprosy reactions are immune-mediated complications of leprosy and remain an important cause of nerve damage, disability, and impaired quality of life despite multidrug therapy. Systemic corticosteroids are used for severe reactions, but recurrent or chronic disease may require prolonged exposure and increase treatment-related toxicity. This systematic review evaluated established and emerging corticosteroid-sparing strategies for type 1 reactions and erythema nodosum leprosum (ENL). PubMed (MEDLINE), ScienceDirect, Cochrane Library, and ProQuest were searched for studies published between January 2017 and October 2026. Eligible trials and observational studies evaluated corticosteroid-sparing therapy in leprosy reactions. Study selection followed PRISMA 2020. Outcomes included clinical response, corticosteroid reduction or withdrawal, recurrence, neurological outcomes, and adverse events. Findings were synthesized qualitatively. Of 363 records identified, 83 duplicates were removed and 280 records were screened. Twelve reports were sought for retrieval, one could not be obtained, and 11 studies involving 722 patients were included. Nine studies focused on ENL, one on type 1 reactions, and one included both reaction types. Thalidomide showed the most consistent corticosteroid-sparing effect, with substantial prednisolone reduction and successful withdrawal reported across several studies. Minocycline achieved earlier ENL control than clofazimine but did not significantly reduce additional prednisolone requirements. Observational studies suggested benefit from methotrexate; however, the MaPs in ENL trial found no reduction in corticosteroid requirement or ENL flares. Etanercept, adalimumab, cyclophosphamide, and secukinumab showed promising activity in refractory ENL, although evidence was limited to small observational studies and case series. Corticosteroid-sparing therapy for leprosy reactions remains supported by heterogeneous and limited evidence, with more data available for ENL than for type 1 reactions. Thalidomide has the most consistent supporting evidence, whereas methotrexate lacks confirmed benefit in randomized data. Biologic and other immunomodulatory therapies remain promising but require larger controlled trials using standardized corticosteroid-sparing, relapse, neurological, and safety outcomes.