Design: Phase 3, randomised 2:1, double-blind, placebo-controlled
Population: 222 adults with moderate-to-severe pemphigus on prednisone 0.5 mg/kg
Primary outcome: Complete remission on minimal prednisone by week 30 (pemphigus vulgaris)
Effect: 35.5% vs 30.3%; OR 1.19 (95% CI 0.60–2.41), P = 0.60

ADDRESS randomised 222 adults with newly diagnosed or relapsing moderate-to-severe pemphigus, 2:1, to subcutaneous efgartigimod with hyaluronidase or placebo, all starting prednisone at 0.5 mg/kg daily. Efgartigimod blocks the neonatal Fc receptor, which normally rescues IgG from breakdown, so it lowers all IgG, including pathogenic autoantibodies.

The primary outcome, complete remission on 10 mg prednisone or less for at least eight weeks by week 30 in pemphigus vulgaris, was reached by 35.5% on efgartigimod and 30.3% on placebo (OR 1.19, 95% CI 0.60–2.41). Total IgG and anti-desmoglein 1 and 3 antibodies fell rapidly, but disease activity scores did not improve more than with steroids alone, and prednisone use was similar. Adverse events were more frequent with efgartigimod (89% vs 76%), serious events similar.

This is a clean pharmacological lesson: the drug hit its target and the surrogate moved, but the patient outcome did not. One explanation is that steroids at 0.5 mg/kg already control much of the disease within 30 weeks, leaving little room. For prescribers, rituximab with steroids remains the established steroid-sparing approach; efgartigimod should not be used in pemphigus on this evidence.

Do not use efgartigimod for pemphigus on current evidence; it did not improve remission over steroids alone.
Keep rituximab with corticosteroids as the established steroid-sparing option in moderate-to-severe pemphigus.
Treat a falling autoantibody level as a surrogate, not proof of clinical benefit, when assessing new immunotherapies.
Expect more adverse events with FcRn blockade, mostly mild to moderate.

Why it matters

It is a clear case of a drug hitting its target and moving a biomarker without helping the patient.

The statistics, in plain English

An odds ratio of 1.19 with an interval from 0.60 to 2.41 means the trial found no meaningful difference and cannot rule out a small benefit or harm. The fall in antibodies was large and fast, which is why the gap between surrogate and outcome is instructive.