There is growing evidence that serum neurofilament light chain (sNfL) and serum glial fibrillary acidic protein (sGFAP) are useful biomarkers in multiple sclerosis (MS). While these biomarkers have been studied in cohorts of MS patients including all disease subtypes (relapsing remitting, secondary progressive, and primary progressive [PP]), few studies have examined biomarker response to treatment in a cohort of exclusively PPMS patients.
To assess how sNfL and sGFAP change over time in PPMS patients who transition from no medication to high potency medication.
Serum samples were collected from 25 patients biannually for 5 years. sNfL and sGFAP were measured using a sensitive single molecule array platform (Quanterix), and log-transformed to assume a normal distribution. Patients were split into two groups based on medication status: patients switched from no medication to a high-potency drug (n=5) versus patients never on medication for the study duration (n=14). Patients on platform drugs or high-potency drugs for the duration of the study were excluded. High-potency drugs include natalizumab, ocrelizumab, fingolimod, and dimethyl fumarate. Statistical analyses were performed in R.
Linear models found sNfL positively associated with age (β=0.024, p=0.004), while higher sGFAP levels were seen in women (β=-0.737, p=0.037). Spaghetti plots examining change in sNfL and sGFAP over five years displayed no trend in either group. Paired Wilcoxon Tests comparing biomarker levels at first versus last available sample showed no significant difference for any group (‘No Drug’ NfL p=0.296, ‘High Potency’ NfL p=0.188; ‘No Drug’ GFAP p=0.583, ‘High Potency’ GFAP p=0.063).
Low levels of NfL are known to accumulate in blood of healthy individuals over time, so the association between sNfL and age is not surprising and has been previously reported. However, sGFAP showed a strong association with female sex; this may be related to a slightly higher average age at enrollment among women. Overall, the spaghetti plots showed little change in either group, with no statistically significant difference in any group over 5 years. This may indicate that these drugs do not affect biomarker level in PPMS. This is further supported by evidence that these immunosuppressive drugs are effective in preventing relapse and inflammatory activity, but may not help to prevent progression. These findings suggest that these biomarkers may have a limited role in judging treatment efficacy in PPMS patients who do not experience flares or new symptoms.