A randomized double-blind trial of intravenous immunoglobulin for pemphigus

Background Pemphigus is a rare life-threatening intractable autoimmune blistering disease caused by IgG autoantibodies to desmogleins. It has been difficult to conduct a double-blind clinical study for pemphigus partly because, in a placebo group, appropriate treatment often must be provided when the disease flares. Objective A multicenter, randomized, placebo-controlled, double-blind trial was conducted to investigate the therapeutic effect of a single cycle of high-dose intravenous immunoglobulin (400, 200, or 0 mg/kg/d) administered over 5 consecutive days in patients relatively resistant to systemic steroids. Methods We evaluated efficacy with time to escape from the protocol as a novel primary end point, and pemphigus activity score, antidesmoglein enzyme-linked immunosorbent assay scores, and safety as secondary end points. Results We enrolled 61 patients with pemphigus vulgaris or pemphigus foliaceus who did not respond to prednisolone (≥20 mg/d). Time to escape from the protocol was significantly prolonged in the 400-mg group compared with the placebo group ( P P P P Limitation Prednisolone at 20 mg/d or more may not be high enough to define steroid resistance. Conclusion Intravenous immunoglobulin (400 mg/kg/d for 5 d) in a single cycle is an effective and safe treatment for patients with pemphigus who are relatively resistant to systemic steroids. Time to escape from the protocol is a useful indicator for evaluation in randomized, placebo-controlled, double-blind studies of rare and serious diseases.