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

ADDRESS was a global phase III double-blind trial in 222 adults with newly diagnosed or relapsing moderate to severe pemphigus (190 vulgaris, 32 foliaceus). All received prednisone from 0.5 mg/kg daily, with either subcutaneous efgartigimod, a neonatal Fc receptor blocker that speeds IgG clearance, or placebo, randomised 2:1.

In pemphigus vulgaris, complete remission on 10 mg or less of prednisone for at least 8 weeks by week 30 occurred in 35.5% with efgartigimod and 30.3% with placebo (OR 1.19, 95% CI 0.60–2.41). Total steroid use did not differ. Efgartigimod rapidly reduced total IgG and anti-desmoglein 1 and 3 antibodies, but disease activity scores did not improve more. Adverse events were 89% against 76%, mostly mild, with similar serious event rates.

The mechanism worked; the outcome did not follow. Lowering circulating IgG was not enough to add benefit to adequate corticosteroid dosing at 30 weeks. Efgartigimod has no supported role in pemphigus on this evidence, and established steroid-sparing options remain the choice.

Do not add efgartigimod to corticosteroids for pemphigus on current evidence.
Continue established steroid-sparing strategies according to dermatology guidance.
Treat falling autoantibody levels as a biomarker, not proof of clinical benefit.
Keep efgartigimod use to its licensed indications.

Why it matters

A drug that clearly hits its target can still fail to help, which is why surrogate response should not drive off-label use.

The statistics, in plain English

An OR of 1.19 with an interval of 0.60–2.41 crosses 1.0 widely, so the trial found no reliable difference. The fall in antibodies was real, but a surrogate marker moving is not the same as patients improving.