To review characteristics of patients with CIDP refractory to first line therapy to help with early identification.

CIDP is an autoimmune disorder of the peripheral nervous system that causes progressive weakness and sensory loss. Approximately 15% of patients are refractory to first line treatment (intravenous or subcutaneous immunoglobulin (IVIG/SCIg), steroids, plasmapheresis), but respond to alternative immunomodulatory therapy such as cyclophosphamide, rituximab, methotrexate, efgartigomod, etc. Early treatment of CIDP improves long term clinical outcomes, therefore, early identification of these patients is essential to reduce delays to effective treatment.

A literature review was conducted in PubMed Central using keywords such as “refractory CIDP” and “IVIG responsiveness in CIDP”. This resulted in 1,269 articles and 2,604 articles, respectively. 79 articles were reviewed that addressed patient responses to IVIG and other first line treatments. Of the 79 articles, 20 were included in this review if specific variables in treatment response and/or demographic data were addressed.

Variables such as age, time to treatment, sex and comorbidities were not shown to be predictors of IVIG responsiveness. Electrodiagnostic testing shows prominent axonal changes with little improvement on post-treatment follow up testing in refractory patients. Genetic biomarkers including gene variation in Ala91Val encoding for perforin 1 is found more often in refractory patients while FcyRIIB protein expression was seen to be upregulated in IVIG responsive patients (ethnic differences noted). The inflammatory marker, neurofilament light chain (nFL), increases with disease onset but does not correlate with IVIg responsiveness. Evaluation of immune response showed group differences in natural kill cell subset populations as soon as 24 hours after treatment.

Further research analyzing genetics, demographic data, immune response, and clinical features may offer a more precise algorithm for identifying these refractory patients prior to their progression to developing severe axonal loss.