Comparison of Efficacy and Safety of Ciclosporin to Prednisolone in the Treatment of Erythema Nodosum Leprosum: Two Randomised, Double Blind, Controlled Pilot Studies in Ethiopia

Abstract

BackgroundErythema Nodosum Leprosum (ENL) is a serious complication of leprosy. It is normally treated with high dose steroids, but its recurrent nature leads to prolonged steroid usage and associated side effects. There is little evidence on the efficacy of alternative treatments for ENL, especially for patients who have become steroid resistant or have steroid side effects. These two pilot studies compare the efficacy and side effect profile of ciclosporin plus prednisolone against prednisolone alone in the treatment of patients with either new ENL or chronic and recurrent ENL.Methods and ResultsThirteen patients with new ENL and twenty patients with chronic ENL were recruited into two double-blinded randomised controlled trials. Patients were randomised to receive ciclosporin and prednisolone or prednisolone treatment only. Patients with acute ENL had a delay of 16 weeks in the occurrence of ENL flare-up episode, with less severe flare-ups and decreased requirements for additional prednisolone. Patients with chronic ENL on ciclosporin had the first episode of ENL flare-up 4 weeks earlier than those on prednisolone, as well as more severe ENL flare-ups requiring 2.5 times more additional prednisolone. Adverse events attributable to prednisolone were more common that those attributable to ciclosporin.ConclusionsThis is the first clinical trial on ENL management set in the African context, and also the first trial in leprosy to use patients’ assessment of outcomes. Patients on ciclosporin showed promising results in the management of acute ENL in this small pilot study. But ciclosporin, did not appear to have a significant steroid–sparing effects in patients with chronic ENL, which may have been due to the prolonged use of steroids in these patients in combination with a too rapid decrease of steroids in patients given ciclosporin. Further research is needed to determine whether the promising results of ciclosporin in acute ENL can be reproduced on a larger scale.

Revised estimates of leprosy disability weights for assessing the global burden of disease: A systematic review and individual patient data meta-analysis

“…Data from eight studies were included in the final meta-analysis. One of the publications [ 27 ] included two pilot trials, which are represented separately in the analysis. Fig 2 provides an overview of the overall disability weights for the Grade 2, Grade 1, and Grade 0 disability from the univariate meta-analysis model, for ease of presentation.…”

Methotrexate and prednisolone study in erythema nodosum leprosum (MaPs in ENL) protocol: a double-blind randomised clinical trial

“…In a study in Ethiopia of 33 participants with ENL, 57% reported GI AEs. 20 An Indian RCT reported 43% of participants experienced GI AEs. 18 ENL is a chronic condition, therefore many study trial participants have a long history of corticosteroid use.…”

“…14 Since the introduction of MDT, there have been eight randomised controlled trials (RCTs) of potential treatments for ENL, involving just 369 (median 22 (range 10-100)) individuals and all had significant methodological limitations including lack of standardisation, allocation concealment and non-validated outcome measures. [15][16][17][18][19][20][21][22] Rationale for using methotrexate Methotrexate (MTX) is an immunosuppressant agent used in the treatment of malignant and inflammatory diseases. 23 24 MTX was first introduced in 1948 to treat acute leukaemia and in 1951, Gubner published his findings on the rapid improvement of psoriasis in patients being treated with aminopterin, an unstable precursor of MTX.…”

Neuropathies of leprosy

“…Studies on giving high dose methylprednisolone did not show an improvement in nerve damage when used to treat reactions and they required additional prednisolone [82]. Also addition of steroid sparing agents like cyclosporin to steroid treatment did not improve nerve damage outcomes in ENL [83].…”