Phase II DAHLIAS Trial: Nipocalimab's Impact on Sjögren Disease

The DAHLIAS trial notes clinically meaningful reductions in disease activity with nipocalimab and supports FcRn blockade as the mechanistic rationale for antibody lowering. The authors interpret these data as suggestive of a potential disease‑modifying signal rather than solely symptomatic relief—an important distinction in a therapeutic area with limited options.

This finding shifts focus from symptomatic management of sicca and systemic features to targeted IgG modulation, moving away from broad immunosuppression. By directly interrupting antibody recycling, FcRn blockade provides a mechanistic strategy with clear clinical relevance, as reductions in pathogenic autoantibodies align with downstream biomarker and symptomatic improvements.

The randomized phase II design enrolled adults with established Sjögren disease who met prespecified diagnostic and activity criteria. Primary efficacy used validated measures, including the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI), assessed at prespecified intervals through the primary analysis window; cohort size was consistent with a phase II proof‑of‑concept study. Efficacy was reported as change from baseline and responder analyses at the primary timepoint, capturing both continuous and categorical signals.

The review reports that nipocalimab was associated with statistically and clinically meaningful decreases in disease activity versus control, with both change‑from‑baseline and responder analyses favoring active treatment. The authors interpret these outcomes as evidence of target engagement based on the available trial data.

Consistent with FcRn inhibition, the trial showed reductions in total IgG and specific autoantibody titres. These biomarker shifts support a plausible mechanistic chain—less antibody recycling leads to fewer immune complexes and reduced autoantibody‑driven tissue injury—linking IgG lowering to the observed clinical effect.

Safety and tolerability in the phase II dataset revealed no unexpected signals. Adverse events were generally low to moderate in severity and occurred at similar overall frequency to comparator arms; common events included infusion‑related reactions and mild infections, while serious adverse events did not cluster or indicate a new safety liability. These findings support continued development.