There is a lack of direct comparison of Immunoglobulin G and M (IgG/IgM) profiles across different B-cell depleting therapies (BCDTs) in MS patients, representing a knowledge gap of associated infection risks. We compared IgG and IgM levels between MS patients on Ocrevus, Kesimpta, and Rituximab and its derivatives. 

140 (64%) were female, 18 (8.2%; average time of treatment 1.4 years) were on Kesimpta, 78 (35.8%;3.9 years) on Ocrevus and 122 (55.9%;1.1 years) on Rituximab. 21 (9.6%) had primary progressive MS (PPMS, average time on BCDTs 3.8 years), 185 (85%) had relapsing remitting MS (RRMS;1.5 years) and 12 (5.5%) had secondary progressive MS (SPMS; 1.6 years). More Ocrevus patients (IgG:17%, IgM:28%) had abnormal IgM and IgG levels (IgG:p=0.07,IgM:p=0.04). More SPMS patients (IgG:42%, IgM:58%) had abnormal IgG and IgM (IgG:p=0.03,IgM:p=0.01). It took longer to observe abnormal levels of IgG/M in patients on Ocrevus (IgG:1.4,IgM:1.5) and longer time periods to observe abnormal levels of IgG/M in PPMS patients (IgG:1.8,IgM:1.0). 

Findings reveal immunological differences between patients on different BCDTs, and the impact of treatment duration on IgG and IgM levels. Longitudinal monitoring of IgG and IgM may be a valuable tool to assess the safety of BCDTs.