Immunotherapies in chronic immune-mediated neuropathies

Steroids and immunoglobulins, either intravenous or subcutaneous, have represented the cornerstone treatment of chronic immune-mediated neuropathies for many years. In the last decade, new therapeutic targets are being studied, with the potential to selectively dampen aberrant immune responses, including drugs that act both on the complement pathways and the recycling mechanism of IgG immunoglobulins by the neonatal receptor (FcRn). Among the latter, efgartigimod has recently been approved for the treatment of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Also rituximab, an anti-CD20 monoclonal antibody mostly used in antimyelin-associated glycoprotein (MAG) antibody neuropathy and in autoimmune nodo-paranodopathies, has been tested both in open and double-blind studies in CIDP, whereas ARGX-117, an antibody targeting the C2 fraction of the complement, is under investigation in multifocal motor neuropathy. In anti-MAG antibody neuropathy, Bruton's tyrosine kinase inhibitors, zanubrutinib and acalabrutinib, are currently tested either as a single agent or in combination with rituximab.