Disease outcomes following lateral switch among different CD20-antibodies in active multiple sclerosis

Background: Ocrelizumab (OCR) and ofatumumab (OFA) are approved and their differences in dosing route and interval allow personalized treatment. However, there are no data on whether lateral switches between both substances affect treatment effectiveness or safety. Methods: We screened our local cohort of MS patients, who began OCR since 09/2020 or OFA since 09/2021. Patients with a lateral switch were matched to controls who continuously received initial B-cell depleting therapy (BCT). We compared disease courses including effectiveness outcomes as well as peripheral CD19+ B-cell counts and serum IgG levels. Results: From 09/2020 to 03/2024, 713 patients were subjected to BCT (OCR: 396; OFA: 317 [as in Fig.1]). The matched OCR cohort included 38 switchers and 149 controls. The OFA cohort consisted of 24 switchers and 83 controls. Effectiveness outcomes were comparable among switchers and controls. B cell depletion appeared slightly pronounced following a switch. Serum IgG levels declined faster among switchers compared to controls (OCR: 9.7 vs 9.0 g/L; p = 0.007; manifest hypogammaglobulinemia (HGG) in 13.2% vs 6.0%; OFA: 9.7 vs 8.4 g/L; p = 0.016; manifest HGG in 8.3% vs 2.4%). Conclusions: Lateral switching between BCT does not abate effectiveness in this matched real-world cohort. Our observation of increased loss of IgG warrants further validation, but may indicate niche-specific immunological effects of OFA and OCR.