Promising role of Fc neonatal receptor blockade in autoimmune rheumatic diseases Save

During the Late-Breaking Abstract session at EULAR 2024, we learned about a novel mechanism of action therapy, nipocalimab in Sjogren’s disease (SjD). This is an anti-neonatal Fc receptor (FcRn) mAb that reduces circulating IgG, including autoantibodies, by selectively blocking the interaction of IgG with FcRn. A phase 2 RCT in moderate to severe active SjD reported that nipocalimab met its primary endpoint of ESSDAI reduction.

A year on at EULAR 2025, data from Phase 2 RCT of efgartigimod, an FcRn-inhibitor were presented in autoantibodies positive, moderate to severe active SjD by Dr Peene at al. (OP0041). I believe that this is the first RCT that uses composite index, CRESS as its primary endpoint. Other key endpoints include another composite measure, STAR, reduction in ESSDAI and patient-reported outcomes. Of 31 patients included in the analysis, the study met its primary endpoint: more responders with ≥3 of 5 CRESS items in the efgartigimod group vs PBO group (45% and 11% respectively). Only 1 of the 5 CRESS items (ESSPRI) did not show a difference between groups. No major safety signal including infection.

In addition to SjD, data from Phase 2 RCT of efgartigimod in inflammatory myopathies also showed that this therapy met its primary endpoint, the 2016 ACR/EULAR Myositis Response Criteria’s Total Improvement Score (TIS) at Week 24, compared to PBO. This was presented by Dr Chinoy at el. (OP0002).

For both indications, efgartigimod is currently evaluated in phase 3 RCTs. Phase 2 RCT in systemic sclerosis is also underway. We look forward to seeing the results of efgartigimod and nipocalimab in Phase 3 RCTs of SjD and IIM. Data from long-extension study are also needed particularly the trajectory of IgG level since low IgG is associated with severe infection.

Whether FcRn blockade can improve patient symptom burden (dryness, fatigue and pain) remains unclear, as well as efficacy in sero-negative SjD.