Hypogammaglobulinemia in patients with multiple sclerosis receiving disease modifying therapies: disproportionality analysis using the EudraVigilance database

Expert Opin Drug Saf. 2025 Apr 16. doi: 10.1080/14740338.2025.2493795. Online ahead of print.

ABSTRACT

BACKGROUND: Monoclonal antibodies targeting CD20, such as rituximab, ocrelizumab, and ofatumumab, are crucial in managing multiple sclerosis (MS). However, they can cause hypogammaglobulinemia, increasing the risk of infections and autoimmune disorders.

RESEARCH DESIGN AND METHODS: This study describes cases of hypogammaglobulinemia in MS patients receiving anti-CD20 monoclonal antibodies, using data from the European spontaneous reporting system database, EudraVigilance.

RESULTS: A total of 135 individual case safety reports (ICSRs), covering 469 adverse drug reactions (ADRs), were retrieved. The majority of ICSRs were related to ocrelizumab (N = 93) and involved cases of hypogammaglobulinemia occurring in adult females. Almost 20% of ICSRs reported concomitant medications, mainly represented by antibiotics, vitamins and antiepileptics. Among the 469 ADRs, 36.8% were serious, and 66% had an unknown outcome. The most commonly reported ADRs belonged to the SOC 'Infections and infestations' and included cases of COVID-19 and respiratory tract infection. Lastly, disproportionality analysis did not show a statistically significant probability of gamma globulin reduction comparing each drug.

CONCLUSIONS: The study highlights the importance of monitoring for the occurrence of hypogammaglobulinemia and infections in patients receiving ocrelizumab, ofatumumab and rituximab for MS. These ADRs can be extremely serious and highlight the need for ongoing research to optimize their safety profiles.

PMID:40235349 | DOI:10.1080/14740338.2025.2493795