Longitudinal changes in serum immunoglobulin levels and peripheral immune cell counts during ocrelizumab treatment in people with multiple sclerosis.

Ocrelizumab is a humanized monoclonal antibody targeting the CD20 antigen on B cells, approved for the treatment of multiple sclerosis (MS). This retrospective observational study investigated the longitudinal immunological effects of ocrelizumab in a real-world cohort of patients with relapsing and progressive MS. Distinct and time-dependent immunological changes emerged, with a marked and early decline in IgM levels, a slower reduction in IgG and IgA levels. As expected with ocrelizumab therapy, CD20+ and CD19+ B-cell counts showed marked and persistent depletion from the first post-treatment assessment. Absolute neutrophil counts, total lymphocytes, and CD8+ T-cell subsets remained remarkably stable across the entire 48-month follow-up and CD4+ T-cell counts presented a tendency toward an increase over time. IgM levels were consistently associated with IgG levels at the same time point and six months later. The mean IgG level over the 48-month treatment period showed a significant association with sex, prior anti-CD20 treatment, and baseline IgM levels. Comparing patients who experienced at least one infectious episode requiring treatment with those without clinically relevant infections, those experiencing an infection had significantly lower pre-event IgG levels than those who remained infection-free (p < 0.001). Consistently, pre-infection serum IgG level was independently associated with subsequent infectious risk (p < 0.001). These findings suggest that the assessment of MS patients treated with ocrelizumab should consider the overall immunological context, integrating humoral and cellular immune parameters alongside clinical characteristics.