Serum neurofilament light chain as a biomarker of disease control in multiple sclerosis: a real-world cross-sectional analysis of therapeutic regimens.

BACKGROUND

Serum neurofilament light chain (sNfL) is an established biomarker of disease activity and progression in persons with multiple sclerosis (PwMS), with studies showing elevated sNfL levels during relapses and positive associations with disability scores.

OBJECTIVE

To assess sNfL levels in PwMS receiving different disease-modifying therapies (DMTs), with a particular focus on extended-interval dosing (EID) regimens in real-world clinical practice.

METHODS

In this two-center cross-sectional study, 172 PwMS without relapses in the preceding three months were included (University Hospital Cologne, n = 125; University Hospital Mainz, n = 47). Patients were categorized into the following groups: (1) low-efficacy DMT (leDMT; n = 8), (2) natalizumab standard-interval dosing (SID; every 4 weeks; n = 7), (3) natalizumab EID (every 6-8 weeks; n = 53), (4) ofatumumab (n = 17), (5) ocrelizumab SID (every 6 months; n = 48), (6) ocrelizumab EID (every 9 months; n = 17), and (7) no DMT (n = 19). sNfL levels were measured once in a cross-sectional design using an electrochemiluminescence immunoassay.

RESULTS

No significant differences in sNfL levels were observed across DMT subgroups in the ANCOVA analysis after adjusting for age and the presence of new T2 lesions on the most recent cranial MRI. However, PwMS receiving DMTs showed lower sNfL levels compared with untreated patients. Notably EID of ocrelizumab (every 9 months; 1.56 pg/mL, 95% CI 1.26-1.85) and natalizumab (every 8 weeks; 1.46 pg/mL, 95% CI 1.29-1.64) was not associated with higher sNfL levels compared to standard interval dosing (SID) of ocrelizumab (1.45 pg/mL, 95% CI 1.27-1.63) or natalizumab (1.13 pg/mL, 95% CI 0.68-1.58).

CONCLUSION

EID regimens were not associated with increased sNfL levels, suggesting that they may effectively limit neuroaxonal damage. Larger studies that assess the added value sNfL monitoring for safely personalizing treatment intervals in PwMS with initially active disease are needed.