To measure neurofilament light chain (NfL) as a biomarker in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP).

CIDP is a rare, progressive, immune-mediated polyneuropathy characterized by proximal and distal weakness and sensory disturbance that can lead to irreversible disability. NfL levels are suggested to reflect axonal damage and may serve as a biomarker of disease activity and treatment response in inflammatory disorders such as CIDP. The efficacy and safety of efgartigimod, a human immunoglobulin (Ig)G1 antibody Fc fragment, were assessed in ADHERE (NCT04281472), the largest CIDP trial to date. 

Participants with active CIDP received open-label, weekly efgartigimod PH20 SC 1000 mg (Stage A) for ≤12 weeks, following withdrawal of standard CIDP treatments. Those with confirmed evidence of clinical improvement entered Stage B and were randomized (1:1) to weekly efgartigimod PH20 SC 1000 mg or placebo for ≤48 weeks. Serum NfL (sNfL) was measured longitudinally in 214 patients, from which NfL z-score (zNfL) was determined.

Mean (SD) NfL levels Stage A baseline was 18.9 (22.6) pg/mL (n=214), corresponding to a mean (SD) zNfL of 0.64 (1.57). Both raw sNfL values and transformed zNfL scores modestly correlated with CIDP disease activity status (CDAS 2-4 vs CDAS 5) (P<0.02). Samples from CIDP-treatment-naïve participants at Stage A baseline exhibited significantly higher zNfL scores compared with those who had previously received CIDP treatment (P=0.05). Stage A baseline zNfL could not differentiate between typical and atypical CIDP. 

The ADHERE trial represents the most extensive dataset of patients with CIDP ever evaluated for NfL. Mirroring previous results, a correlation was identified between baseline NfL levels and CDAS scores, with higher levels indicating more active disease. Although NfL levels could not differentiate between typical and atypical CIDP, it may serve as a contextual biomarker, alongside clinical assessment. Further analysis will determine whether NfL can inform on disease prognosis and monitoring.