Abstract

BACKGROUND

Pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are rare, chronic, potentially life-threatening, immunoglobulin (Ig)G-mediated, autoimmune skin and/or mucosal blistering diseases. Efgartigimod, a human IgG1 antibody Fc fragment, blocks the neonatal Fc receptor, decreasing IgG recycling and reducing both healthy and pathogenic IgG autoantibody levels.

OBJECTIVES

To investigate the efficacy, safety and impact of subcutaneous efgartigimod PH20 (co-formulated with recombinant human hyaluronidase PH20) in conjunction with prednisone in the treatment of pemphigus.

METHODS

Adult participants with newly diagnosed or relapsing moderate-to-severe pemphigus were recruited in this phase III, prospective, multicentre, randomised, double-blinded, placebo-controlled study (NCT04598451). Participants were randomised (2 : 1) to weekly subcutaneous efgartigimod PH20 or placebo. Subcutaneous efgartigimod PH20 2000 mg was administered on days 1 and 8, followed by 1000 mg weekly until complete remission on minimal prednisone therapy (CRmin) (≤ 10 mg daily). All participants received concomitant prednisone starting at 0.5 mg kg-1 daily. The primary outcome was the proportion of participants with PV who achieved CRmin by week 30, while receiving minimal prednisone, for ≥ 8 weeks. Pharmacodynamics and safety were also assessed.

RESULTS

Overall, 222 participants (PV: n = 190; PF: n = 32) were randomised (subcutaneous efgartigimod PH20: n = 147; placebo: n = 75). The proportions of participants with PV achieving CRmin within 30 weeks were comparable between the subcutaneous efgartigimod PH20 and placebo groups, with no statistically significant difference observed [44/124 (35.5%) vs. 20/66 (30.3%); P = 0.60; odds ratio 1.19 (95% confidence interval 0.60-2.41)]. Total prednisone consumption over time was comparable between groups. Subcutaneous efgartigimod PH20 resulted in rapid reductions from baseline in total IgG and anti--desmoglein-1 and anti-desmoglein-3 autoantibody levels, but these did not translate to improvements in Pemphigus Disease Area Index scores. The rates of adverse events (AEs) in the subcutaneous efgartigimod PH20 and placebo groups were 89.1% (n = 131/147) and 76.0% (n = 57/75), respectively; most were mild to moderate [serious AEs: 12.2% (n = 18/147) and 13.3% (n = 10/75), respectively]. No deaths occurred.

CONCLUSIONS

Subcutaneous efgartigimod PH20 in combination with systemic corticosteroids did not demonstrate clinical benefit over systemic corticosteroids alone in patients with moderate-to-severe pemphigus at 30 weeks, but it was well tolerated in this patient population.

MeSH

Syphilis, Safety, Prednisone, Adrenal Cortex Hormones, Desmogleins, Therapeutics, Pemphigus, Dermatology