Prevalence of hypogammaglobulinemia after non-anti-CD20 therapies and impact of switching to rituximab/ocrelizumab in multiple sclerosis

Some people with multiple sclerosis (PwMS) exhibit reduced serum immunoglobulin (Ig) levels, potentially due to disease-modifying therapies (DMTs), which raises concerns about initiating anti-CD20 therapies. We assessed the frequency of hypogammaglobulinemia in PwMS who previously received non-anti-CD20 DMTs and evaluated short-term Ig level changes after switching to rituximab (RTX) or ocrelizumab (OCR). This retrospective study included PwMS starting RTX or OCR, with or without prior DMT exposure. Patients were grouped as treatment-naïve or receiving fingolimod (FING), natalizumab (NTZ), or moderate-efficacy DMTs (interferons, glatiramer acetate, dimethyl fumarate, or teriflunomide) before the switch. Among 417 included patients, 89 were treatment-naïve, 207 had received FING, 70 NTZ, and 51 moderate-efficacy DMTs. Before switching, hypogammaglobulinemia (IgG level <7 ​g/L) was rare in treatment-naïve and moderate-efficacy DMT groups (2 ​%) but more frequent after FING (29 ​%) and NTZ (14 ​%) treatment. One year after initiating RTX/OCR, IgG level slightly decreased in treatment-naïve patients (p ​< ​0.05), remained stable in NTZ and moderate-efficacy DMT groups, and increased significantly in FING-treated patients (8.0-8.6 ​g/L, p ​< ​0.0001), with a decline in hypogammaglobulinemia prevalence (29 ​%-21.5 ​%). FING exposure was associated with frequent IgG hypogammaglobulinemia, but switching to RTX/OCR was not linked to a short-term decrease in IgG level; instead, it led to a significant increase in level. These findings support that hypogammaglobulinemia should not be an absolute contraindication to switching to RTX/OCR after FING discontinuation given their efficacy in preventing MS reactivation. A secondary de-escalation strategy may be considered based on individual risk profiles and IgG level trajectories.