Evaluation and treatment of refractory chronic inflammatory demyelinating polyradiculoneuropathy

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an inflammatory, immune-mediated neuropathy of the peripheral nerves and nerve roots. CIDP is unlikely to be a discrete disease entity, but rather a spectrum of related conditions, in which cell-mediated and humoral mechanisms act synergistically to cause damage to peripheral nerves. The 2021 guideline of the European Academy of Neurology/Peripheral Nerve Society on the diagnosis and treatment of CIDP has modified the CIDP spectrum to include typical CIDP and four well-defined CIDP variants. Patients with CIDP usually respond well to immunoglobulin therapy, steroids or plasmapheresis; however, 20-30% do not respond well, and approximately 15% remain refractory to all treatment modalities. Rituximab, mycophenolate mofetil and cyclophosphamide are of therapeutic benefit for some of these patients. Patients with some CIDP variants respond less well to immunotherapy, suggesting a difference in the pathogenic mechanisms underlying these variants. Potential novel treatments trialled in CIDP, targeting functionally relevant disease mechanisms, include neonatal Fc receptor blockers and complement inhibitors. These new treatment approaches are needed to optimise disease outcomes in refractory patients, and as an alternative for patients with suboptimal response requiring high doses or experiencing side effects from first-line therapies. Increasing the therapeutic options for patients with CIDP, particularly for refractory patients, highlights the need for more accurate diagnosis of typical CIDP and CIDP variants, objective evidence of treatment response and the need for reliable clinical biomarkers.