Plasma NfL and GFAP predict disability worsening in non-active secondary progressive MS

Conference

AAN 2021

Trial

Phase 3, EXPAND

In a post-hoc analysis of the EXPAND study, a biosignature of combined high plasma neurofilament light chain (pNfL) and high plasma (p)GFAP consistently indicated an elevated risk of disability worsening in non-active secondary progressive MS patients. The added value of combining GFAP and NfL was less apparent in active secondary progressive MS.

EXPAND (NCT01665144) was a randomised, double-blind, phase 3 trial of siponimod in secondary progressive MS patients [1]. In this post-hoc analysis, which included the open-label extension period, baseline pNfL and pGFAP levels were determined using Single Molecule Array technology [2]. Samples from 1,369 patients were available for analysis.

In 704 patients with non-active secondary progressive MS, combined high pNfL and high pGFAP had relatively higher hazard ratios for all disability outcomes versus combined low pNfL and low pGFAP:

time to EDSS 7.0 (HR 2.65; P=0.0014);
time to 1-point sustained EDSS worsening (HR 1.57; P=0.0176);
time to 3-month confirmed disability worsening (HR 1.45; P=0.0151).

Hazard ratios were also higher (range: 2.09–1.17) with a high pNfL + low pGFAP signature across all 3 outcomes (P=0.05). In 665 patients with active secondary progressive MS, the prognostic value of baseline levels of pNfL and pGFAP individually or in combination was weaker. Further analyses are ongoing, investigating other cut-offs and considering potential differential and time-dependent treatment effects.

Kappos L, et al. Lancet. 2018;391(10127):1263-73.
Kuhle J, et al. Plasma Neurofilament Light Chain and Glial Fibrillary Acidic Protein Levels Are Prognostic of Disability Worsening: A Biosignature That Helps Differentiating Active From Non-active SPMS. P11.001, AAN 2021 Virtual Congress, 17-22 April.

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