Efgartigimod Shows Early Promise for Primary Sjögren’s Disease

For decades, systemic treatment options for primary Sjögren’s disease (pSjD) have been limited to symptom management, with no disease-modifying therapies approved to target its immune-driven pathology.

Now, data from the phase 2 RHO trial, presented at the European Congress of Rheumatology in June, 2025 suggest that efgartigimod may offer an immunomodulatory approach. Efgartigimod selectively lowers serum IgG, including the pathogenic autoantibodies in pSjD, by binding the neonatal Fc receptor or FcRn, and inhibiting IgG recycling, without suppressing antibody production or albumin levels.

Here’s a look at how the study was designed, what it found, and how these results may impact pSjD care.

A Targeted Mechanism Meets a Rigorous Clinical Trial Framework
RHO was a multicenter, randomized, double-blind, placebo-controlled proof-of-concept trial involving adults with moderate-to-severe pSjD (ESSDAI ≥5, anti-Ro/SSA positive).

Participants (n=34) were randomized 2:1 to receive weekly intravenous efgartigimod or placebo for 24 weeks. The primary endpoint was defined by response to greater than or equal to three of five domains in the Composite of Relevant Endpoints for Sjögren’s Syndrome (CRESS). Secondary endpoints included the candidate Sjögren’s Tool for Assessing Response (cSTAR), as well as changes in ESSDAI, ClinESSDAI, ESSPRI, and exploratory biomarkers.

Efficacy Signal and IgG Reduction
Taking a look at the results, the study found the following:

• Primary endpoint met: 45.5 percent (10/22) of patients receiving efgartigimod were CRESS responders, with improvements in four out of five clinical domains (salivary and tear gland function, systemic activity, and serology) versus 11.1 percent (1/9) in the placebo group.
• cSTAR responses favored efgartigimod (54.5 percent, 12/22) over placebo (33.3 percent, 3/9).
• Biomarker data showed rapid and sustained IgG reductions: there was a mean 58.3 percent reduction in total IgG and 63.8 percent reduction in anti-Ro52 from week four onward.
• Reductions were also observed in RF levels (19.6 percent)andC1Q immune complexes (4.0 μg Eq/mL)—both relevant to B-cell activation and immune complex-driven inflammation in pSjD.

Well-Characterized Safety Profile
Efgartigimod was well tolerated with no new safety signals, consistent with prior data in myasthenia gravis and immune thrombocytopenia. Importantly, albumin levels remained unaffected, underscoring the selective mechanism of FcRn blockade without compromising systemic immunity.

A Step Toward Disease Modification
The results validate FcRn blockade as a rational therapeutic strategy in pSjD, particularly for patients with active systemic disease and elevated autoantibody burden. By reducing circulating pathogenic IgG while preserving immune surveillance, efgartigimod may offer an alternative to broad immunosuppression.

Furthermore, the trial’s use of composite and candidate response metrics reflects a growing consensus around more nuanced outcome measures in Sjögren’s research—recognizing both glandular function and systemic immune activity.

Looking Ahead: UNITY Phase 3 Underway
Based on the RHO findings, the UNITY trial (NCT06684847) is now enrolling patients with higher systemic disease activity (ClinESSDAI ≥6) to assess efficacy in a larger population. This pivotal trial will be key in determining whether efgartigimod can become the first disease-modifying therapy approved for primary Sjögren’s.

Reference:
Peene I, Verstappen GM, Deprez J, et al. Treatment of primary Sjögren’s disease by blocking FcRn: clinical and translational data from RHO, a phase 2 randomized, placebo-controlled, double-blind, proof-of-concept study with efgartigimod. Oral presentation at EULAR; June 11-14, 2025: Barcelona, Spain. doi:10.1136/annrheumdis-2025-eular.2515.