Multicenter randomized, double-blind, placebo-controlled, clinical trial of dapsone as a glucocorticoid-sparing agent in maintenance-phase pemphigus vulgaris

Objective: To determine the efficacy of dapsone as a glucocorticoid-sparing agent in maintenance-phase pemphigus vulgaris (PV). Design: A randomized, double-blind, placebo-controlled study with a crossover arm for those who failed treatment. Setting: A US multicenter outpatient study. Patients: A total of 19 subjects enrolled among 5 centers, 9 randomized to receive dapsone and 10 to receive placebo. Inclusion criteria were biopsy and direct immunofluorescence- proven PV controlled with glucocorticoids and/or cytotoxic agents, disease in maintenance phase, and aged 18 to 80 years. Physicians had tried at least 2 tapers of glucocorticoids unsuccessfully and had 30 days of stable steroid dosage. Treatment for any patient unable to taper glucocorticoids by more than 25% within 4 months was declared a failure, and the patient was allowed to switch to the opposite medication while maintaining the double-blind. Main Outcome Measure: The ability of patients to taper to 7.5 mg/d or less within 1 year of reaching the maximum dosage of the study drug. Results: Of the 9 patients receiving dapsone, 5 were successfully treated, 3 failed treatment, and 1 dropped out of the study. Of the 10 patients receiving placebo, 3 were successfully treated, and 7 failed treatment. This primary end point favored the dapsone-treated group but was not statistically significant (P=.37). Four patients who failed treatment while receiving placebo were switched to treatment with dapsone. Of these, 3 were successfully treated after switching to dapsone treatment, and 1 failed treatment. We found that, overall, 8 of 11 patients (73%) receiving dapsone vs 3 of 10 (30%) receiving placebo reached the primary outcome of a prednisone dosage of 7.5 mg/d or less. Conclusion: This trial demonstrates a trend to efficacy of dapsone as a steroid-sparing drug in maintenancephase PV. Trial Registration: clinicaltrials.gov Identifier: NCT00429533.