A Randomized Controlled Double Blind Trial of Ciclosporin versus Prednisolone in the Management of Leprosy Patients with New Type 1 Reaction, in Ethiopia

Background: Leprosy Type 1 (T1R) reactions are immune-mediated events leading to nerve damage and preventable disability affecting hands, feet and eyes. Type 1 Reactions are treated with oral corticosteroids. There is little evidence on alternative treatments for patients who do not respond to steroids or experience steroid adverse effects. We report the results of a randomized controlled trial testing the efficacy and adverse effect profile of ciclosporin and prednisolone (CnP) in comparison to prednisolone only (P) in patients with new T1R in Ethiopia. Ciclosporin is a potent immunosuppressant. Outcomes were measured using a clinical severity score, recurrence rate, adverse events and quality of life. Results: Seventy three patients with new T1R were randomized to receive CnP or P for 20 weeks. Recovery rates in skin signs was similar in both groups (91% vs 88%). Improvements in nerve function both, new and old, sensory (66% vs 49%) and motor (75% vs 74%) loss were higher (but not significantly so) in the patients on CnP. Recurrences rates of T1R (85%) were high in both groups, and recurrences occurred significantly earlier (8 weeks) in patients CnP, who needed 10% more additional prednisolone. Serious major and minor adverse events rates were similar in patients in the two treatment arms of the study. Both groups had a significant improvement in their quality of life after the study, measured by the SF-36. Conclusions: This is the first double-blind RCT assessing ciclosporin, in the management of T1R in Africa. Ciclosporin could be a safe alternative second-line drug for patients with T1R who are not improving with prednisolone or are experiencing adverse events related to prednisolone. This study illustrates the difficulty in switching off leprosy inflammation. Better treatment agents for leprosy patients with reactions and nerve damage are needed. Author Summary: Leprosy infection is cured with multi-drug therapy (MDT), but patients may develop immune mediated skin and nerve lesions. These immunological reactions lead to disability and deformity secondary to neuropathy. Prednisolone is the main drug used to treat reactions but is only partially effective and patients have a high rate of side effects. Identifying better agents for treating leprosy reactions is an important clinical goal. We tested the safety and efficacy of ciclosporin, an immunosuppressant used in many inflammatory conditions, in Type 1 reactions (T1R) in leprosy patients in Ethiopia. A double-blind randomized controlled clinical trial comparing the efficacy and adverse event profiles of ciclosporin and prednisolone was conducted in patients presenting with acute T1R. Patients on ciclosporin and prednisolone had similar improvements in clinical outcomes which were measured as skin and nerve function improvement. Both groups had a high rate of T1R recurrence (85%) and the patients on ciclosporin required more additional prednisolone to treat recurrences. We assessed patient quality of life and this was significantly improved with both treatments. This is the first assessment of patient quality of life in a leprosy patients trial. Ciclosporin may be a useful alternative in the treatment of T1R, but that the need for additional steroids decreases its value.