Immunotherapy in Chronic Inflammatory Demyelinating Polyneuropathy and the Emerging Role of Efgartigimod

and the Emerging Role of EfgartigimodChronic inflammatory demyelinating polyneuropathy (CIDP) is an acquired immune-mediated neuropathy that causes chronic or relapsing sensorimotor deficits due to segmental demyelination of peripheral nerves, with symptoms persisting for more than 8 weeks.The pathogenesis involves both cellular and antibody-mediated (humoral) immune mechanisms targeting peripheral myelin antigens that result in inflammatory demyelination, secondary axonal degeneration, and conduction block.CIDP is a significant cause of progressive disability, making timely diagnosis and effective treatment essential.CIDP is rare but increasingly recognized, with the reported prevalence ranging from 1 to 9 per 100,000 population.1,2 The disease affects all age groups, but is most common in adults aged between 40 and 60 years, with a male predominance.1,2 CIDP has a heterogeneous clinical presentation, ranging from the typical symmetric sensorimotor form to atypical variants such as MADSAM (multifocal acquired demyelinating sensory and motor neuropathy), DADS (distal acquired demyelinating symmetric neuropathy), pure sensory, and pure motor forms.Distal-predominant sensorimotor forms of CIDP have been recognized as anti-MAG neuropathies, while recent studies have identified that the nodopathies caused by anti-NF155 antibodies are distinct entities from classical CIDP.3,4 Diagnosing CIDP relies on a combination of clinical, electrophysiologic, and laboratory findings, including from cerebrospinal fluid analysis, MRI or ultrasonography of nerve roots and plexuses, and nerve biopsy.Imaging markers also provide additional support according to the updated 2021 EAN/PNS guidelines.5 Immunomodulation is the mainstay of CIDP therapy.Corticosteroids, intravenous immunoglobulin (IVIg), and plasma exchange are traditionally considered first-line treatments, with strong evidence supporting their efficacy in improving strength and reducing disability.5 Maintenance therapy may involve periodic IVIg infusions or an oral immunosuppressant such as azathioprine, mycophenolate mofetil, or cyclosporine to prevent relapse.However, long-term corticosteroid use is associated with significant side effects, and IVIg therapy can present substantial logistics and financial challenges, especially for patients requiring chronic maintenance.The real-world data indicate that a substantial proportion of patients respond suboptimally to standard immunotherapies, highlighting the heterogeneity of the underlying pathogenic mechanisms.Reliable biomarkers for guiding diagnoses, predicting treatment responses, and monitoring disease activity are lacking.Furthermore, the absence of head-to-head trials between immunotherapeutic regimens restricts the evidence-based personalization of therapy.The accessibility and cost of long-term IVIg therapy also pose global health-equity concerns.Moreover, approximately 30% of patients receiving the standard treatment for CIDP remain refractory, leading to accumulating disability and impairment.6 Recent emerging strategies are aimed at moving beyond nonspecific immunosuppression toward precision medicine.7 Among these, therapies that reduce immunoglobulin G (IgG)