Immunoglobulin dynamics and infection risk with ofatumumab versus ocrelizumab in multiple sclerosis

To evaluate the impact of ofatumumab versus ocrelizumab on immunoglobulin levels in people with multiple sclerosis (pwMS).

Consecutive pwMS treated with ofatumumab (N = 321) or ocrelizumab (N = 328) were enrolled. Predictors of low IgG and IgM levels were assessed using multivariable logistic regression, including sex, Expanded Disability Status Scale (EDSS) score, prior disease-modifying therapy (DMT), disease duration, treatment type, baseline immunoglobulin levels, and age at treatment initiation. Predictors of infections were analyzed using multivariable logistic regression, including treatment type and duration, demographic and clinical variables, and early declines in IgG and IgM.

Compared with the ofatumumab group, pwMS treated with ocrelizumab had longer disease duration, higher EDSS scores, and were less likely to be treatment-naïve (all p < 0.001). No significant differences were observed between groups in the proportion of pwMS with IgG or IgM levels below the lower limit of normal. Prior DMT exposure reduced the risk of low IgG at months 6 and 12, whereas baseline IgG predicted low IgG from months 6-36. Baseline IgM predicted low IgM throughout follow-up. In the whole cohort, only female sex (Exp(B)=1.608, 95% CI 1.097-2.359, p = 0.015), prior DTM exposure (Exp(B)=1.575, 95% CI 1.003-2.474, p = 0.048) and longer treatment duration (Exp(B)=1.628, 95% CI 1.417-1.870, p < 0.001) predicted infections.

Ofatumumab and ocrelizumab have comparable effects on immunoglobulin levels. Baseline immunoglobulin levels and treatment duration, rather than treatment choice, are the primary determinants of hypogammaglobulinemia and infection risk, supporting individualized monitoring strategies.