A phase 2 clinical trial published in the Annals of the Rheumatic Diseases has demonstrated encouraging results for intravenous efgartigimod in adults with moderate-to-severe systemic Sjögren’s disease (SjD). The study provided proof of concept that targeting pathogenic immunoglobulin G (IgG) autoantibodies through neonatal Fc receptor (FcRn) inhibition may offer a promising therapeutic strategy for this chronic autoimmune disorder, for which no approved systemic disease-modifying therapy currently exists.
Sjögren’s disease is a systemic autoimmune condition characterized by immune-mediated damage to exocrine glands and multiple organs. Although disease-modifying antirheumatic drugs are frequently used off-label to manage specific organ manifestations, current treatment largely focuses on symptomatic relief, highlighting the substantial unmet need for targeted therapies capable of modifying disease activity.
Efgartigimod is an engineered human IgG1 antibody Fc fragment that binds with high affinity to the neonatal Fc receptor (FcRn), preventing the recycling of IgG antibodies and promoting the selective reduction of circulating IgG, including pathogenic autoantibodies. The therapy does not interfere with antibody production or other components of the immune system and does not affect serum albumin or low-density lipoprotein (LDL) levels. The drug is already approved for the treatment of generalized myasthenia gravis in the United States, European Union, Japan, and China, primary immune thrombocytopenia in Japan, and chronic inflammatory demyelinating polyradiculoneuropathy in several countries.
The multicentre, randomized, double-blind, placebo-controlled phase 2 RHO study evaluated the efficacy and safety of intravenous efgartigimod in adults with moderate-to-severe systemic Sjögren’s disease. Participants were randomized in a 2:1 ratio to receive intravenous efgartigimod (10 mg/kg) or placebo once weekly for 24 weeks. Of the 34 participants enrolled, 23 received efgartigimod and 11 received placebo, while 31 participants were included in the efficacy analysis.
At week 24, 45.5% of patients treated with efgartigimod achieved improvement in at least three components of the Composite of Relevant Endpoints for Sjögren’s Syndrome (CRESS), compared with 11.1% of those receiving placebo, representing a treatment difference of 34.4% points. Improvements were observed across four of the five CRESS domains. Additionally, 54.5% of patients receiving efgartigimod achieved a Clinical Systemic Activity Response Tool (cSTAR) score of at least five, compared with 33.3% in the placebo group.
The study also demonstrated rapid pharmacodynamic activity, with total IgG concentrations declining by approximately 60% from baseline following treatment. This reduction supports the proposed mechanism of FcRn inhibition in decreasing pathogenic autoantibody levels associated with Sjögren’s disease.
Efgartigimod was generally well tolerated throughout the study. Treatment-emergent adverse events were reported in 87% of patients receiving efgartigimod and 63.6% of those receiving placebo; however, all reported adverse events were mild to moderate (grade 1 or 2), and no unexpected safety concerns were identified.
According to the investigators, the findings provide important proof of concept that pathogenic autoantibodies contribute to the pathophysiology of Sjögren’s disease and that FcRn inhibition may represent a viable disease-modifying therapeutic approach. The positive numerical improvements observed across multiple clinical endpoints support further clinical development of efgartigimod in this patient population.
Building on these encouraging phase 2 results, a phase 3 registrational trial is currently underway to evaluate the safety and efficacy of subcutaneous efgartigimod in individuals with Sjögren’s disease. If successful, the therapy could become one of the first targeted systemic treatments approved specifically for patients with this debilitating autoimmune disease.
Reference
Peene I, Verstappen GM, Arends S, Kroese FGM, De Boeck K, Achten H, et al. Efgartigimod in Sjögren’s disease: a phase 2, randomised, placebo-controlled, parallel-group, double-blinded, proof-of-concept study (RHO). Ann Rheum Dis. 2026 Jul;85(7):1341-1350.