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

Background: Erythema 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 results: Thirteen 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.

Conclusions: This 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.

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1. CONSORT flow diagrams for the pilot studies of individuals with new ENL (a) and with chronic ENL (b), randomised to either ciclosporin and prednisolone or prednisolone alone.

Fig 2. Time of first recurrence of ENL after initial control patients with new ENL (a) and patients with chronic ENL (b).

Fig 3. Number and severity ENL flare-up episodes in patients with new ENL (a) and chronic ENL (b).

Fig 4. Mean amount of additional and total prednisolone prescribed in patients with new ENL (a) and patients with chronic ENL (b).

Fig 5. Change in SF-36 scores between start and end of study in patients with new ENL (a) and patients with chronic ENL (b).

PF-physical functioning, RP-role physical, BP-bodily pain, GH-general health perceptions, VT-vitality, SF-social functioning, RE-role emotional, MH-mental health, PCS-physical component summary, MCS-mental component summary.