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

Abstract

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.

Fig 1. CONSORT flow diagram.

Fig 2. Group mean and standard error in Clinical Severity Scores with time by treatment arm.

Score A (skin), Score B (sensation) and Score C (motor). (0 marks the area in Score A where the difference between the treatment arms is significant).

Fig 3. Median and inter-quartile ranges in Clinical Severity Scores.

Fig 4. Motor function change in nerves with new weakness.

Fig 5. Sensory function change in nerves with new loss of sensation.

Fig 6. Survival curve for patients without a T1R recurrence.

Fig 7. Time of first recurrence of T1R after initial control.

Fig 8. Number of T1R recurrence episodes per treatment arm.

Fig 9. Number of T1R recurrence episodes by Clinical Severity Score.

Fig 10. Weekly mean prednisolone per patient by treatment arm.

Fig 11. Change in SF-36 scores between start and end of T1R study.

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.