idursulfase + rituximab + methotrexate + intravenous immunoglobulin

This drug refers to a combination of four agents: - **Idursulfase**, a recombinant enzyme used for enzyme replacement therapy (ERT) in Hunter syndrome (mucopolysaccharidosis II, MPS II), which functions by replacing deficient iduronate-2-sulfatase - **Rituximab**, a monoclonal antibody targeting CD20 on B cells, leading to B-cell depletion - **Methotrexate**, a small-molecule antimetabolite and immunosuppressant that inhibits dihydrofolate reductase and other folate-dependent enzymes - **Intravenous immunoglobulin (IVIG)**, pooled immunoglobulin G (IgG) from healthy donors, providing immune modulation and passive immunity This specific combination is used as an **immune tolerance induction (ITI) and immune modulation protocol** in patients with MPS II who are at risk for, or have developed, high-titer neutralizing anti-idursulfase antibodies that reduce the efficacy of ERT. The combination aims to prevent or reduce immune responses against the therapeutic enzyme by depleting B cells, suppressing antibody production, and modulating the immune system. Protocols have been based on similar regimens used for immune tolerance in other lysosomal storage diseases, especially in patients with factors that increase immunogenicity risk[1][3][9][5][7].