Selective IgM Hypogammaglobulinemia and Multiple Sclerosis Treated with Natalizumab and Ofatumumab: A Case Report

<b>Background:</b> B-cell-depleting drugs targeting the CD20 antigen have been increasingly implemented as an "exit strategy" from natalizumab for relapsing-remitting multiple sclerosis (RRMS) patients due to the increased risk of progressive multifocal leukoencephalopathy. Data on recently approved anti-CD20 drugs, such as ofatumumab serving as a natalizumab "exit strategy", are lacking. Furthermore, due to their immunosuppressive mechanism of action, prolonged use of these "highly effective" drugs is associated with the development of hypogammaglobulinemia and, consequently, a higher risk of infections. There are no guidelines for monitoring serum immunoglobulin levels in individuals undergoing "highly effective" multiple sclerosis treatment. <b>Methods:</b> We present a case of a 26-year-old male RRMS patient with selective IgM deficiency and multiple sclerosis initially treated with natalizumab and later ofatumumab. <b>Results:</b> The patient achieved "no evident disease activity "status while undergoing treatment with natalizumab and ofatumumab, but these therapies, especially ofatumumab, greatly impacted further drops in IgM levels. However, no significant decrease in IgG levels was observed, and no infectious events occurred. In addition, the patient did not show signs of disease activity while on ofatumumab, which also offered a more convenient mode of administration. <b>Conclusions</b>: Our experience points to the need to further explore benefit-risk ratios of highly effective treatments, even in cases with low immunoglobulin levels. However, closely monitoring immunoglobulin levels and conducting clinical follow-ups to ensure prompt recognition of potential infectious complications constitute approaches that have been thought of for such patients.