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

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. Author Summary: Leprosy is caused by a mycobacterium, and is curable with multi-drug therapy, a combination of antibiotics taken for 6 or 12 months. However, some leprosy patients develop an inflammatory condition known as erythema nodosum leprosum (ENL), or Type 2 reaction. ENL affects multiple organs and causes systemic illness as well as nerve damage that leads to disability and deformity. ENL is often chronic and patients have multiple flare-ups requiring prolonged steroid treatment. Patients are at risk of developing adverse events related to long term steroids. There are no effective, non-teratogenic alternative treatments for patients who no longer respond to steroids or have contra-indications to steroids. We conducted two studies to see if ciclosporin, an immunosuppressant used in many inflammatory conditions, could safely be used either as an alternative or in conjunction with prednisolone to treat ENL. Patients with acute ENL showed promising results with ciclosporin treatment, with a 16 week median delay in recurrence of ENL. It did not however appear to have a significant steroid–sparing effects in patients with chronic ENL. This suggests that further ENL studies should look at carefully tailored regimens of medication in order to assess the effect of ciclosporin or other immunosuppressant drugs.