EFGARTIGIMOD pemphigus treatment did not demonstrate a clinical benefit over corticosteroids alone in adults with moderate-to-severe pemphigus, despite rapidly reducing immunoglobulin G (IgG) and pathogenic autoantibody levels.
The phase III, prospective, multicentre, randomised, double-blind, placebo-controlled trial included adults with newly diagnosed or relapsing moderate-to-severe pemphigus vulgaris (PV) or pemphigus foliaceus (PF). Participants were randomised 2:1 to receive weekly subcutaneous efgartigimod PH20 or placebo alongside prednisone.
A total of 222 participants were randomised, including 190 with PV and 32 with PF. Of these, 147 received efgartigimod PH20 and 75 received placebo. Treatment consisted of 2000 mg on days one and eight, followed by 1000 mg weekly until complete remission on minimal prednisone therapy (CRmin), defined as remission while receiving ≤10 mg prednisone daily.
The primary outcome was the proportion of participants with PV achieving CRmin by week 30 for at least eight weeks.
Among participants with PV, 44 of 124 (35.5%) receiving efgartigimod achieved CRmin within 30 weeks compared with 20 of 66 (30.3%) receiving placebo. The difference was not statistically significant (odds ratio: 1.19; 95% confidence interval [CI]: 0.60–2.41; p=0.60).
Total prednisone consumption over time was also comparable between groups. Efgartigimod produced rapid reductions from baseline in total IgG and anti-desmoglein-1 and anti-desmoglein-3 autoantibody levels, but these reductions did not translate into improvements in Pemphigus Disease Area Index scores.
Adverse events occurred in 131 of 147 participants (89.1%) receiving efgartigimod and 57 of 75 (76.0%) receiving placebo. Most adverse events were mild to moderate.
Serious adverse events occurred in 18 participants (12.2%) in the efgartigimod group and 10 (13.3%) in the placebo group. No deaths occurred during the study.
The researchers concluded that subcutaneous efgartigimod PH20 combined with systemic corticosteroids did not provide clinical benefit over corticosteroids alone at 30 weeks in patients with moderate-to-severe pemphigus. However, the treatment was well tolerated, while producing rapid reductions in IgG and pemphigus-associated autoantibodies.
Reference
Joly P et al. Efficacy and safety of subcutaneous efgartigimod with prednisone in moderate-to-severe pemphigus (ADDRESS): a global, phase III, randomised controlled, double-blind trial. Br J Dermatol. 2026;DOI: 10.1093/bjd/ljag199.
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