Prednisolone adverse events in the treatment and prevention of leprosy neuropathy in two large double blind randomized clinical trials 

Objectives

To document serious adverse events (SAE) of prolonged prednisolone use in two double-blind randomized clinical trials (RCT). In the first RCT, treatment effectiveness on restoring nerve function of a 20-week prednisolone regimen was compared with a 32-week course. In the second RCT, patients with subclinical neuropathy received either 20 weeks prednisolone or placebo to assess whether prednisolone could prevent the development of clinical neuropathy.  In both trials, patients received a prednisolone starting dose according to weight: high weight (≥50 kg) started at 60 mg and low weight (<50 kg) at 45 mg. In both trials, the occurrence of serious adverse events (SAE) was an important secondary outcome.

Results

In the first RCT, 868 patients were enrolled, of whom 16 (1.8%) developed a serious adverse event (SAE). There were 12 SAEs in the longer treatment arm (N = 439, event rate of 2.7%), and four in the shorter arm (N = 429, event rate of 0.9%) (p = 0.041). In the second RCT 4/364 (1.1%) developed an SAE, of which one was in the placebo arm. In both trials, minor adverse events were quite common and varied greatly in frequency and between centres.

Conclusions

When searching for the optimum dose and duration of prednisolone in the treatment and prevention of neuropathy in leprosy patients, one must weigh possible advantages against the possible serious adverse events. Although our trials showed a significantly increased percentage of SAE in the longer treatment arm in the first RCT and in the treatment arm of the second RCT, the overall event rate was very low.