Hypogammaglobulinemia and severe infections in multiple sclerosis patients on anti- CD20 agents: A multicentre study

Background and Aims: Hypogammaglobulinemia (HG) is a known side effect of treatment with anti- CD20 monoclonal antibodies, and it is associated with the risk of infections. Aim of this retrospective multicentre study was to assess the frequency of HG in Multiple Sclerosis (MS) and Neuromyelitis Optica Spectrum Disease patients treated with ocrelizumab (OCR) or rituximab (RTX) and its association with the occurrence of infections requiring hospitalization (SI). Methods: We included 556 patients (190M, 366F) treated for at least one year with either OCR or RTX. Results: The mean age was 47 years and mean follow- up of 28 months. IgG HG occurred in 20% and IgM HG in 34% of patients. The risk of IgG HG was influenced by an older age (≥50 years) (OR 1.67, 95% CI: 1.08–2.61, p = 0.022), previous immunosuppressive therapy (OR 1.60, 95% CI: 1.04–2.48, p = 0.033) and by the number of treatment cycles (OR: 1.19, 95% CI: 1.08–1.31, p = 0.004). A total of 25 SI occurred (100 person- years rate: 1.8), with a disease phenotype other than relapsing- remitting (OR 1.50, 95% CI: 1.02–2.20; p = 0.039) and IgG HG (OR 2.65, 95% CI: 1.15–6.12; p = 0.022) increasing its risk. Conclusion: IgG and IgM HG occurred in a considerable proportion of patients. IgG HG increased the risk of SI, which were, nevertheless, relatively infrequent. Our results highlight the importance of monitoring immunoglobulin levels to personalize treatment strategies.