Neurofilament light chain predicted confirmed disability worsening at 1 to 2 years in MS

Key takeaways:

• The study examined more than 1,800 adults with MS from two study cohorts.
• The findings help understand the evidence for association between neurofilament light chain and confirmed disability worsening.

For those with multiple sclerosis, presence of elevated neurofilament light chain biomarkers was associated with symptom progression that predicted clinical disease worsening within 1 to 2 years, according to research from JAMA Neurology.

The link between [neurofilament light chain] levels and confirmed disability worsening in [multiple sclerosis] is poorly understood and partly contradictory,” Ahmed Abdelhak, MD, clinical instructor at the Weill Institute for Neurosciences and the department of neurology at the University of California, San Francisco, and colleagues wrote.

Abdelhak and colleagues sought to determine whether and when neurofilament light chain (NfL) levels are elevated in the context of confirmed disability worsening (CDW) for those with MS.

Their observational study included two cohorts from tertiary MS treatment centers: one from the Expression, Proteomics, Imaging, Clinical (EPIC) study at the University of California, San Francisco, which was confirmed in the Swiss Multiple Sclerosis Cohort (SMSC), a multicenter study conducted in eight centers since 2012. Data were extracted from EPIC in April 2022 (from 3,906 visits for 609 participants between July 1, 2004, to Dec. 20, 2016; median age 42 years; 69.6% female) and SMSC in December 2022 (from 8,901 visits for 1,209 participants between June 6, 2012, to Sept. 2, 2021; median age 41.2 years; 65.9% female).

The primary outcome was CDW, defined as Expanded Disability Status Scale (EDSS) worsening confirmed after 6 or more months and classified into CDW associated with clinical relapses (CDW-R) or independent of clinical relapses (CDW-NR).

Visits were classified as CDW(2) for two visits preceding event, CDW(1) for directly preceding event, CDW(event) for first diagnosis of EDSS increase as well as a confirmation visit. Mixed linear and Cox regression models were utilized to evaluate the association of NfL with future CDW.

According to results, in CDW-R (EPIC, 36 events; SMSC, 93 events), NfL z scores were 0.71 (95% CI, 0.35-1.07) units higher at CDW-R(1) in EPIC and 0.32 (95% CI, 0.14-0.49) in SMSC compared with stable MS samples. Elevation of NfL could be detected preceding CDW-NR (EPIC,191 events; SMSC, 342 events) at CDW-NR(2) (EPIC: 0.23; 95% CI, 0.01-0.45; SMSC: 0.28; 95% CI, 0.18-0.37) and at CDW-NR(1) (EPIC: 0.27; 95% CI, 0.11-0.44; SMSC: 0.09; 95% CI, 0-0.18).

Researchers further found that time-to-event analysis confirmed the association between NfL levels and future CDW-R withinapproximately 1 year and CDW-NR within a range of 1 to 2 years.

“Our findings help understand the complex landscape of conflicting evidence for association between [neurofilament light chain] and [confirmed disability worsening],” Abdelhak and colleagues wrote.