A46-05 Pleuropericarditis Linked to Ocrelizumab: Expanding the Spectrum of Anti-CD20-related Toxicity

Ocrelizumab, an anti-CD20 monoclonal antibody, used for multiple sclerosis (MS) by reducing relapse and delaying disability progression in both relapsing and primary progressive forms. Rare immune-mediated complications continue to emerge with increasing clinical use. Reported adverse events include organizing pneumonia, immune colitis, and viral reactivation syndromes ; however, cardiac and serosal inflammatory events remain uncommon. A 41-year-old male with relapsing multiple sclerosis on long-term ocrelizumab presented with chest discomfort pleuritic in character and dyspnea for 2 days. Imaging revealed bilateral pleural effusions, pericardial effusion, and multifocal consolidations suggestive of pneumonia. He was treated empirically with antibiotics. Echocardiography showed a moderate pericardial effusion without tamponade. He was treated for acute inflammatory pericarditis based on symptoms, echocardiography findings, elevated ESR, and CRP. Symptoms resolved with ibuprofen taper and colchicine, and repeat echocardiography showed near-complete resolution. He subsequently re-presented with recurrent pleuritic pain and shortness of breath. Broad infectious work-up was unrevealing. Thoracentesis yielded exudative lymphocyte predominant pleural fluid, negative for cytology and culture. Autoimmune testing revealed positive ANA (1:320, speckled pattern) and anti-Scl-70 antibody positivity. He had no clinical features of any connective tissue diseases. Given persistent serosal inflammation, lack of infection, and isolated serologic findings, ocrelizumab-induced autoimmune serositis was suspected. Neurology recommended discontinuation of ocrelizumab and transition to alternative therapy. The patient remains clinically stable on anti-inflammatory therapy with close follow-up. Anti-CD20 monoclonal antibodies, particularly ocrelizumab, have shown favorable safety profiles in clinical trials. However, pharmacovigilance data studies have raised emerging concerns regarding potential cardiovascular toxicities, including atrial fibrillation, cardiac failure, and coronary artery disease, reported in approximately 3.4-5.8% of patients treated with agents such as daclizumab, ocrelizumab, or ofatumumab. Although cardiac and serosal complications remain rare, isolated cases of viral pericarditis following ocrelizumab therapy and bacterial endocarditis or fatal myocarditis associated with rituximab have been described. The underlying mechanism remains incompletely understood but may involve aberrant immune reconstitution or dysregulated B-cell repopulation following prolonged CD20 depletion, leading to cytokine-mediated inflammation and autoantibody formation. In our case, the presence of ANA and anti-Scl-70 positivity without clinical features of connective tissue disease suggests that these autoantibodies may represent secondary, drug-induced autoimmune activation. This case shows the importance of recognizing pericarditis and pleural effusion as possible complications of ocrelizumab therapy. Early awareness of this association can prevent diagnostic delays, prompt termination of therapy, and guide appropriate management. Currently, no consensus exists regarding re-initiation of therapy following pericarditis, emphasizing the need for further research. This abstract is funded by: None