Design: Phase 3, randomised 2:1, double-blind, placebo-controlled
Population: 222 adults with moderate-to-severe pemphigus (190 vulgaris, 32 foliaceus)
Primary outcome: Complete remission on ≤10 mg prednisone for ≥8 weeks by week 30 (pemphigus vulgaris)
Effect: 35.5% vs 30.3%, OR 1.19 (95% CI 0.60–2.41); P = 0.60

ADDRESS, a phase 3 double-blind trial published in the British Journal of Dermatology on 11 September, randomised 222 adults with new or relapsing moderate-to-severe pemphigus 2:1 to weekly subcutaneous efgartigimod or placebo. All received prednisone from 0.5 mg/kg daily. Efgartigimod blocks the neonatal Fc receptor and lowers IgG, including pathogenic autoantibodies.

In pemphigus vulgaris, complete remission on 10 mg prednisone or less by week 30 was similar: 35.5% with efgartigimod and 30.3% with placebo (OR 1.19, 0.60 to 2.41). Total steroid use did not differ. IgG and anti-desmoglein 1 and 3 levels fell quickly, but disease activity scores did not improve more. Adverse events were more frequent with efgartigimod (89.1% vs 76.0%); serious events were similar.

A fall in autoantibodies did not become clinical benefit. Current first-line care, steroids with rituximab where appropriate, is unchanged, and this trial gives no reason to add FcRn blockade.

Do not add efgartigimod to steroids for pemphigus on the strength of current evidence.
Continue established first-line treatment, including rituximab where indicated.
Do not treat falling desmoglein antibody levels alone as evidence of a drug's clinical effect.
Keep steroid-sparing as the goal and track cumulative prednisone dose.

Why it matters

Lowering the antibody that causes pemphigus was not enough to change its course, which challenges a common assumption.

The statistics, in plain English

An odds ratio of 1.19 with an interval from 0.60 to 2.41 is compatible with anything from a moderate harm to a moderate benefit, so the trial found no clear effect. A small benefit cannot be fully excluded.