Efgartigimod in Sjögren’s disease: a phase 2, randomised, placebo-controlled, parallel-group, double-blinded, proof-of-concept study (RHO)

OBJECTIVES: This study aimed to evaluate the efficacy and safety of intravenous (IV) efgartigimod in adults with Sjögren's disease (SjD). METHODS: We conducted a randomised, double-blinded, placebo-controlled, phase 2, proof-of-concept multicentre study (hereafter referred to as RHO). Participants were randomised 2:1 to receive efgartigimod IV 10 mg/kg or placebo once weekly for 24 weeks. The primary outcome was the proportion of Composite of Relevant Endpoints for Sjögren's Syndrome (CRESS) responders on ≥3 of 5 items (systemic disease activity, patient-reported symptoms, tear and salivary gland function, and serology) at week 24. Secondary outcomes included the proportion with candidate Sjögren's Tool for Assessing Response (cSTAR) score ≥5 at week 24 and safety. No formal statistical hypothesis was tested. RESULTS: Thirty-four participants were randomised to efgartigimod (N = 23) or placebo (N = 11); 31 were included in the efficacy analysis. A numerically higher proportion of efgartigimod-treated participants responded to ≥3 items of CRESS at week 24 compared with placebo (45.5% vs 11.1%; treatment difference 34.4%). More specifically, efgartigimod scored higher on 4 of 5 CRESS items. Similarly, a numerically higher proportion of efgartigimod-treated participants scored ≥5 on the cSTAR at week 24 (efgartigimod, 54.5% vs placebo, 33.3%). Treatment-emergent adverse events were reported in 87.0% of efgartigimod-treated participants compared with 63.6% of those on placebo; all were grade 1 or 2 in severity. CONCLUSIONS: Data from the RHO study support proof of concept for efgartigimod in SjD. Further evaluation in a phase 3 study of efgartigimod in individuals with SjD is warranted. The trial was registered with ClinicalTrials.gov (NCT05817669).