Abstract
Objectives To evaluate the prognostic value of 3- and 12-month on-treatment serum neurofilament light chain (sNfL) levels for future disease activity in with relapsing multiple sclerosis[pwRMS]
Methods A baseline sNfL cut-off was predefined by the median sNfL value across the ofatumumab ASCLEPIOS I/II Phase 3 clinical trials and participants were stratified into high (≥baseline median [≥9.3 pg/mL]) and low (<median) sNfL groups at Month (M) 3 and M12, irrespective of treatment received. The prognostic value of high versus low sNfL at M3 and M12 was analyzed for the annualized rate of new/enlarging T2 (neT2) lesions. The number of neT2 lesions on the last available scan relative to the M12 scan was analyzed in a negative binomial model with time (in years) between the two scans as offset, adjusting for sNfL category at the respective month.
Results Of the 1,882 participants randomized in ASCLEPIOS I/II, 1,393 and 1,384 participants had neT2 and sNfL data at M3 andM12, respectively. Participants with high versus low sNfL at M3 had a ~2.2-fold higher mean annualized rate of neT2 lesions (3.67versus 1.69, rate ratio [RR]: 2.17; p<0.001). Similarly, participants with high versus low sNfL at M12 had a ~3.6-fold higher mean annualized rate of neT2 lesions (4.90 versus 1.37, RR: 3.57; p<0.001).
Conclusions On-treatment sNfL levels at 3 and 12 months continue to be prognostic for future lesion formation and support the use of sNfL as a prognostic biomarker for MS disease activity in pwRMS on disease-modifying therapy.
