Secondary hypogammaglobulinemia in patients with multiple sclerosis on anti-CD20 therapy: Pathogenesis, risk of infection, and disease management

Hypogammaglobulinemia and infections in patients with multiple sclerosis treated with anti-CD20 treatments: a systematic review and meta-analysis of 19,139 multiple sclerosis patients

“…Various disease-modifying therapies for MS differ in mechanisms, efficacy, and safety profiles, with a focus on targeting the immune response ( 53 ). Anti-CD20 therapies such as rituximab, ocrelizumab, ofatumumab, and ublituximab have proven effective and well-tolerated in MS patients through clinical trials, thereby expanding treatment options ( 54 ). Specifically, the anti-CD20 monoclonal antibodies ofatumumab and ocrelizumab, approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA), demonstrate efficacy in relapsing multiple sclerosis (RMS) by delaying disease progression, reducing relapses, and limiting new lesion formations on brain scans ( 55 , 56 ).…”

“…Hypogammaglobulinemia can manifest during prolonged anti-CD20 therapy ( 60 , 61 ). One hypothesis suggests that despite anti-CD20 treatment not directly affecting IgG and IgM-producing plasma cells, it delays the regeneration of B-cells ( 54 ). Reports indicate the time required for B-cell regeneration post-treatment: 24 weeks for ofatumumab, 72 weeks (ranging 27–175) for ocrelizumab, and 70 weeks (ranging 0.1–75) for ublituximab ( 56 ).…”

“…These regenerated naive B cells display reduced ability to become plasma cells, leading to decreased IgG and IgA production while still capable of producing IgM ( 61 ). This suggests that the impact of anti-CD20 therapies on immunoglobulin levels might involve complex interactions between different types of B cells, affecting humoral immunity ( 54 , 63 , 64 ).…”

“…Analysis of Gastrointestinal (GIT) infections among the included studies. treatment options (54). Specifically, the anti-CD20 monoclonal antibodies ofatumumab and ocrelizumab, approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA), demonstrate efficacy in relapsing multiple sclerosis (RMS) by delaying disease progression, reducing relapses, and limiting new lesion formations on brain scans (55,56).…”

Drugs Targeting CD20 in Multiple Sclerosis: Pharmacology, Efficacy, Safety, and Tolerability

“…There have been only a few head-to-head comparisons of the risk of hypogammaglobulinemia and infection among different anti-CD20 mAbs, although the risk is reported to be lower with ofatumumab compared to rituximab and ocrelizumab [ 42 ]. This difference could be due to differences in affinity for the target epitope or route of administration, as SC antibody administration induces less B-cell depletion in the spleen as opposed to IV administration [ 34 ].…”