Unveiling the Uncommon: Infective Endocarditis Following Ocrelizumab Therapy in Relapsing-Remitting Multiple Sclerosis

Abstract Ocrelizumab is an anti-CD20 monoclonal antibody approved for relapsing-remitting multiple sclerosis (RRMS) that induces B-cell depletion and may increase susceptibility to infection via hypogammaglobulinemia; however, serious bloodstream infections are uncommon, and infective endocarditis (IE) is rare. We describe a 20-year-old man with RRMS, hypertension, class II obesity, and type 2 diabetes who developed persistent fever 7 days after receiving a 300-mg ocrelizumab infusion, with blood cultures growing Staphylococcus aureus. Transesophageal echocardiography demonstrated a 4-mm mobile vegetation on the atrial aspect of the P2 scallop of the posterior mitral leaflet; chest computed tomography revealed bilateral peripheral nodules consistent with hematogenous infection, and cardiac magnetic resonance imaging suggested concomitant myocarditis. The patient completed 6 weeks of intravenous cefazolin with full clinical recovery, clearance of bacteremia, and echocardiographic resolution of the vegetation. To our knowledge, this represents the second published case report of S. aureus IE temporally associated with ocrelizumab therapy. Although causality cannot be established, anti-CD20-mediated B-cell depletion may be associated with increased infection risk in susceptible hosts, particularly those with cardiometabolic comorbidities and recent corticosteroid exposure. These findings underscore the importance of early evaluation for serious infection, including IE, in patients initiating ocrelizumab who present with persistent fever or bacteremia.