Methotrexate as a corticosteroid-sparing agent in leprosy reactions: A French multicenter retrospective study

Author summaryLeprosy reactions (LRs) are acute inflammatory episodes that complicate 30% to 50% of Mycobacterium leprae infections. Type 1 is known as reversal reaction (RR), and type 2 is known as erythema nodosum leprosum (ENL). The two types have relatively distinct pathogenesis and clinical features; furthermore, they can advance to become severe and progress to irreversible nerve damage and deformities. Beyond leprosy infection, LR can bring about neurological burden, poor quality of life, and risk of further descent into poverty for often young patients. Despite effective standardized treatment of leprosy infection with multidrug therapy (MDT) since 1981, treating LRs prove to be challenging. First-line treatment of LR is based on prolonged systemic glucocorticoids (GCs) therapy. The current challenge in leprosy is now to develop and evaluate new therapeutic alternatives to reduce not only the sequelae and morbidity of LR but also the lasting side effects of GCs. Thalidomide is an effective alternative in moderate to severe ENL, but its use is limited given its numerous adverse effects. Methotrexate (MTX) is an immunomodulating agent used to treat inflammatory diseases and has an excellent safety profile and worldwide availability. Here, we describe the efficacy, GCs-sparing effect, and safety of MTX in LR. IntroductionLeprosy reactions (LRs) are inflammatory responses observed in 30%-50% of people with leprosy. First-line treatment is glucocorticoids (GCs), often administered at high doses with prolonged courses, resulting in high morbi-mortality. Methotrexate (MTX) is an immunomodulating agent used to treat inflammatory diseases and has an excellent safety profile and worldwide availability. In this study, we describe the efficacy, GCs-sparing effect and safety of MTX in LRs. MethodsWe conducted a retrospective multicentric study in France consisting of leprosy patients receiving MTX for a reversal reaction (RR) and/or erythema nodosum leprosum (ENL) since 2016. The primary endpoint was the rate of good response (GR) defined as the complete disappearance of inflammatory cutaneous or neurological symptoms without recurrence during MTX treatment. The secondary endpoint was the GCs-sparing effect, safety and clinical relapse after MTX discontinuation. ResultsOur study included 13 patients with LRs (8 men, 5 women): 6 had ENL and 7 had RR. All patients had had at least one previous course of GCs and 2 previous treatment lines before starting MTX. Overall, 8/13 (61.5%) patients had GR, allowing for GCs-sparing and even GCs withdrawal in 6/11 (54.5%). No severe adverse effects were observed. Relapse after MTX discontinuation was substantial (42%): the median relapse time was 5.5 months (range 3-14) after stopping treatment. ConclusionMTX seems to be an effective alternative treatment in LRs, allowing for GCs-sparing with a good safety profile. Furthermore, early introduction during LRs may lead to a better therapeutic response. However, its efficacy seems to suggest prolonged therapy to prevent recurrence.

Automated summary

Leprosy reactions (LRs) are complications of leprosy infection that can cause nerve damage and deformities. Current treatment with glucocorticoids has significant side effects. However, methotrexate has been identified as an effective alternative that can reduce the need for glucocorticoids and their side effects.