FCGR3A Polymorphism Controls B-Cell Repopulation Kinetics in People With Multiple Sclerosis Treated With Ocrelizumab

BACKGROUND AND OBJECTIVES: V158F polymorphism affects its efficacy in MS remains unclear. Here, we tested whether this genetic variant influences B-cell repopulation and disease activity in MS participants treated with OCR and assessed genotype-dependent differences in OCR binding to FcγRIIIa-expressing natural killer (NK) cells. METHODS: B cells ≥1%. Secondary outcomes included clinical and MRI inflammatory activity and composite disease activity/disability-worsening measures. In a parallel mechanistic ex vivo substudy, OCR or rituximab (RTX) binding to NK cells was evaluated in genotype-selected donors by flow cytometry. Cycle-based repeated measures were analyzed using mixed-effects logistic regression. DISCUSSION: V158F polymorphism and B-cell repletion kinetics can inform optimized interval-based OCR dosing in MS.