Prognostic Value of Serum NfL for Predicting Lesion Formation in MS Affirmed by ASCLEPIOS I/II

People with relapsing multiple sclerosis (RMS) who had higher 3- and 12-month on-treatment serum neurofilament light chain (sNfL) levels were found to have higher annualized rates of new or emerging T2 (neT2) lesion formation, according to findings from the phase 3 ASCLEPIOS I/II clinical trials (NCT02792218/NCT02792231). The findings, which demonstrate the prognostic value of sNfL levels for future RMS disease activity, were presented at the American Academy of Neurology (AAN) 2024 Annual Meeting.

ASCLEPIOS I/II were double-blind, double-dummy studies comparatively evaluating the safety and efficacy of Kesimpta (ofatumumab; Novartis, East Hanover, NJ) vs Aubagio (teriflunomide; Sanofi, Bridgewater, NJ) as treatments for RMS. The study population included a total of 1882 participants who were randomized to receive either subcutaneous Kesimpta or Aubagio. Participants were stratified into a high sNfL group if their sNfL levels met or were higher than the total population’s median sNfL level. Participants with sNfL levels lower than the median level of the total population were stratified into a low sNfL group. sNfL levels were assessed at months 3 and 12 of the study and were compared to the annualized rate of neT2 lesion formation.

At months 3 and 12, 1393 and 1384 participants had neT2 and sNfL data, respectively.

• Participants had an approximately 2.2-fold higher mean annualized rate of neT2 lesions if they were in the high sNfL group at 3 months, compared to the low sNfL group (3.67 vs 1.69; rate ratio [RR], 2.17; P<.001).
• At 12 months, participants in the high sNfL group had an approximately 3.6-fold higher annualized rate of neT2 lesions, as compared to the low sNfL group (4.90 vs 1.37; RR, 3.57; P<.001).

The study authors are affiliated with Thomas Jefferson University, the University of California, San Francisco (UCSF) Weill Institute for Neurosciences, University Hopsital Basel, the University of Münster, McGill University, Vall d’Hebron University Hospital, University of Colorado School of Medicine, University Hospital Carl Gustav Carus, and Novartis.