Efficacy and safety of subcutaneous efgartigimod with prednisone in moderate-to-severe pemphigus (ADDRESS): a global, phase III, randomised controlled, double-blind trial.
Pascal Joly, Dedee F Murrell, Yumi Aoyama et al.
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In 30 seconds
ADDRESS was a global, phase III, multicentre, randomised, double-blind, placebo-controlled trial of adults with newly diagnosed or relapsing moderate-to-severe pemphigus. Participants received weekly subcutaneous efgartigimod PH20 or placebo, alongside prednisone. Among participants with pemphigus vulgaris, complete remission on minimal prednisone by week 30, sustained for at least 8 weeks, occurred in 35.5% with efgartigimod and 30.3% with placebo (P = 0.60; odds ratio 1.19, 95% confidence interval 0.60-2.41). The trial found no clinical benefit over prednisone alone, despite reductions in IgG and pemphigus autoantibodies.
Key findings
- Complete remission on minimal prednisone by week 30 occurred in 44/124 (35.5%) with efgartigimod and 20/66 (30.3%) with placebo; P = 0.60.
- Prednisone consumption over time was comparable between groups, and antibody reductions with efgartigimod did not translate to improved Pemphigus Disease Area Index scores.
- Adverse events occurred in 89.1% (n = 131/147) with efgartigimod and 76.0% (n = 57/75) with placebo; serious adverse events occurred in 12.2% and 13.3%, respectively.
Why it matters
The trial illustrates that lowering total IgG and disease-associated autoantibodies does not necessarily improve clinical outcomes in pemphigus. For clinicians assessing therapies that target disease mechanisms, the patient-centred remission outcome is important alongside pharmacodynamic effects. In this study, adding efgartigimod to prednisone did not improve remission over prednisone alone by 30 weeks.
What to keep in mind
The primary efficacy outcome was assessed in participants with pemphigus vulgaris; the abstract does not report a corresponding efficacy result for the smaller pemphigus foliaceus group.