Neurofilament Light Chain Levels Track Disease Activity and Decline With Efgartigimod Treatment in CIDP

An exploratory analysis of the phase 3 ADHERE trial (NCT04281472) featured among the abstracts at the 2026 Peripheral Nerve Society (PNS) Annual Meeting in Maastricht, Netherlands found that serum neurofilament light chain (sNfL) levels correlated with disease activity at baseline and declined with efgartigimod PH20 SC (Vyvgart Hytrulo; argenx) treatment in patients with elevated levels.¹ Drawn from the largest CIDP dataset to date evaluated for NfL, the findings add to growing interest in the biomarker as a monitoring tool in inflammatory neuropathies.

Led by Roger Collet Vidiella, MD, of the Neuromuscular Diseases Unit at the Hospital de la Santa Creu i Sant Pau in Barcelona, Spain, the analysis evaluated sNfL longitudinally in 214 participants from the ADHERE trial and derived NfL z-scores (zNfL) to account for age-related variation in healthy reference ranges.

Study Design

Participants with probable or definite active CIDP, confirmed by treatment withdrawal during a run-in phase, received open-label weekly subcutaneous efgartigimod PH20 1000 mg during stage A for up to 12 weeks. Responders were then randomized 1:1 to continue efgartigimod PH20 SC 1000 mg weekly or placebo for up to 48 weeks in stage B. Serum NfL was measured longitudinally throughout both stages in the 214-participant biomarker analysis set.

Key Findings

At stage A baseline, mean sNfL was 18.9 pg/mL (SD 22.6), corresponding to a mean zNfL of 0.64 (SD 1.57). Of the 214 participants, 24.3% had sNfL levels above the healthy reference range (greater than 20 pg/mL), which investigators noted may indicate ongoing axonal damage at treatment initiation.¹

Baseline zNfL scores were significantly higher in participants with unstable CIDP disease activity status (CDAS 2 to 4) compared with those with stable active disease (CDAS 5; P = .03). Baseline zNfL was also highest in treatment-naive participants versus those who had previously received CIDP therapy, consistent with greater ongoing axonal injury in earlier, untreated disease.¹

Among stage A responders, sNfL levels followed two distinct patterns by baseline level. In those with sNfL within the healthy reference range at baseline (20 pg/mL or less; n = 114), levels remained stable throughout stage A. In those with elevated baseline sNfL (greater than 20 pg/mL; n = 36), levels declined by 18% over the course of stage A treatment.¹ In participants who continued receiving efgartigimod through stage B, sNfL reduced by a further 35% by week 24 (n = 13), with continued decline observed through week 48 in those who remained on active treatment. The data from stage B are limited by small sample sizes beyond week 12.

NfL z-scores at baseline were comparable across CIDP disease types (typical CIDP versus atypical CIDP; P = .51), suggesting the biomarker may be relevant across the heterogeneous CIDP spectrum.

Clinical Significance

NfL is a structural protein released from damaged axons into the bloodstream, with serum levels reflecting the degree of ongoing neuroaxonal injury independent of the underlying disease mechanism. In healthy individuals, mean serum NfL values by age have been reported as 13 to 20 pg/mL, corresponding to zNfL of 1.5 or less.¹ Its potential utility in CIDP has been constrained in prior studies by small sample sizes, heterogeneous patient populations, and limited longitudinal follow-up, limitations that the ADHERE dataset is positioned to address.

The investigators concluded that NfL may serve as a contextual biomarker in CIDP when interpreted alongside clinical assessment, particularly in patients with elevated baseline levels or dynamic changes over time. Further analysis will examine whether NfL can inform prognosis or guide disease monitoring decisions in clinical practice.

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REFERENCES
1. Collet Vidiella R, Caballero-Avila M, Casneuf T, et al. Neurofilament light chain as a biomarker in chronic inflammatory demyelinating polyradiculoneuropathy: insights from ADHERE. Abstract submitted to: Peripheral Nerve Society Annual Meeting; June 13-16, 2026; Maastricht, Netherlands. Abstract P 372.
2. van Lieverloo GGA, Wieske L, Verhamme C, et al. Serum neurofilament light chain in chronic inflammatory demyelinating polyneuropathy. J Peripher Nerv Syst. 2019;24(2):187-194. doi:10.1111/jns.12315. https://doi.org/10.1111/jns.12315
3. argenx announces FDA approval of Vyvgart Hytrulo for chronic inflammatory demyelinating polyneuropathy. News release. argenx. June 21, 2024. Accessed June 14, 2026. https://www.us.argenx.com/news/argenx-announces-fda-approval-vyvgart-hytrulo-chronic-inflammatory-demyelinating-polyneuropathy