mepolizumab + rituximab

Mepolizumab + rituximab is a combination therapy consisting of two monoclonal antibodies, each with distinct mechanisms of action targeting different components of the immune system. Mepolizumab is a fully humanized IgG1 kappa monoclonal antibody that binds to interleukin-5 (IL-5), preventing it from binding to its receptor and thereby reducing eosinophil production and survival. Rituximab is a chimeric monoclonal antibody targeting the CD20 antigen on B lymphocytes, leading to B-cell depletion through complement-dependent cytotoxicity and antibody-dependent cell-mediated cytotoxicity. This combination has been used off-label for refractory cases of eosinophilic granulomatosis with polyangiitis (EGPA), particularly when standard therapies such as glucocorticoids or cyclophosphamide are insufficient or contraindicated. The rationale for combining these agents lies in their complementary immunomodulatory effects—mepolizumab primarily suppresses eosinophilic inflammation, while rituximab targets pathogenic B cells involved in autoantibody production and vasculitic processes[1][2][4].