Multiple Sclerosis News TodayNerve Damage Marker Linked to Lower Daily Activity in Progressive MS

ℹ️ Observational Association Only Evidence

Researchers analyzed data from the Phase 3 SPI2 trial to examine whether blood neurofilament light chain (NfL), a biomarker of neuroaxonal injury, is associated with real-world ambulatory function in progressive multiple sclerosis (MS). The analysis included 506 participants with paired NfL and wearable-derived step-count data collected over approximately 27 months. Investigators found that higher NfL z-scores were associated with lower daily step counts, and participants whose NfL levels increased more rapidly over time tended to experience greater declines in physical activity. Because this was an observational analysis, the findings identify an association between biological and functional measures but did not establish causality.

Clinical Considerations

• The cohort included 506 patients with progressive MS, including both secondary progressive and primary progressive disease.
• Median baseline ambulatory activity was 3,029 daily steps, reflecting a population with substantial disability.
• Each 1-point increase in NfL z-score was associated with approximately 3.4% fewer daily steps.
• A reverse association was also observed, with a 10% increase in daily step count associated with a 0.015-point lower NfL z-score.
• Participants whose NfL levels increased more rapidly over time experienced greater declines in ambulatory activity, although the observed relationship was modest.
• Analyses evaluating whether early NfL changes predicted later reductions in activity showed a directional relationship, but several findings did not reach statistical significance.
• Investigators noted that generalizability remains uncertain for individuals with less disability or for relapsing forms of MS.

Practice Applications

• Interpret NfL as a biomarker associated with functional status in progressive MS rather than a standalone measure of disease progression.
• Recognize that wearable-derived mobility metrics may provide complementary information alongside biological markers and traditional disability assessments.
• Evaluate biomarker findings within the broader clinical context, including disability measures, symptoms, imaging findings, and treatment history.
• Monitor emerging evidence exploring combined biological and functional endpoints in progressive MS trials.
• Avoid assuming that changes in physical activity directly cause changes in NfL levels or vice versa, as causality was not established.