Efficacy and safety of subcutaneous efgartigimod with prednisone in moderate-to-severe pemphigus (ADDRESS): a global, phase III, randomised controlled, double-blind trial

Pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are rare, chronic, potentially life-threatening, immunoglobulin (Ig)G-mediated, autoimmune skin and/or mucosal blistering diseases. Efgartigimod, a human IgG1 antibody Fc fragment, blocks the neonatal Fc receptor, decreasing IgG recycling and reducing both healthy and pathogenic IgG autoantibody levels.

To investigate the efficacy, safety and impact of subcutaneous efgartigimod PH20 (co-formulated with recombinant human hyaluronidase PH20) in conjunction with prednisone in the treatment of pemphigus.

Adult participants with newly diagnosed or relapsing moderate-to-severe pemphigus were recruited in this phase III, prospective, multicentre, randomised, double-blinded, placebo-controlled study (NCT04598451). Participants were randomised (2 : 1) to weekly subcutaneous efgartigimod PH20 or placebo. Subcutaneous efgartigimod PH20 2000 mg was administered on days 1 and 8, followed by 1000 mg weekly until complete remission on minimal prednisone therapy (CRmin) (≤ 10 mg daily). All participants received concomitant prednisone starting at 0.5 mg kg-1 daily. The primary outcome was the proportion of participants with PV who achieved CRmin by week 30, while receiving minimal prednisone, for ≥ 8 weeks. Pharmacodynamics and safety were also assessed.