To assess whether neurofilament light chain (NfL) levels measured before and during ocrelizumab treatment were associated with brain volume (BV) changes in patients with primary progressive multiple sclerosis (PPMS) or relapsing MS (RMS).

Blood NfL is a biomarker of neuroaxonal injury that correlates with disease activity in MS. In previous studies, NfL predicted relapses, Expanded Disability Status Scale (EDSS) score worsening and BV loss. Ocrelizumab significantly reduced brain atrophy and NfL levels in RMS and PPMS.

Longitudinal blood NfL and brain MRI data from patients with PPMS (ORATORIO; n=399) or RMS (OPERA I; n=477) were analyzed. Brain atrophy was calculated as percentage BV change (PBVC) from Week 24 to the end of the controlled treatment period (ORATORIO, Week 120; OPERA I, Week 96). Log-transformed NfL, normalized BV (NBV), log-transformed T2 lesion volume (T2LV), T1 gadolinium-enhancing lesion count, age and EDSS score at baseline were examined for associations with brain atrophy. In the ocrelizumab arms, log(NfL) at Weeks 12, 24, 48, 72, 96 and 120 (ORATORIO only) was assessed for associations.

Baseline NfL (−0.18 and −0.19 PBVC per SD, both p<0.001), NBV (+0.13 [p=0.005] and +0.09 PBVC [p=0.014] per SD), T2LV (−0.21 [p<0.001] and −0.09 [p=0.018] PBVC per SD), age >45 (+0.23 [p=0.008] and +0.18 [p=0.017] PBVC) and subsequent ocrelizumab treatment (+0.25% BV vs placebo [p=0.004] and +0.19% BV vs interferon β-1a [p=0.002]), were independently associated with PBVC in patients with PPMS and RMS, respectively. Following ocrelizumab initiation, NfL levels at Weeks 12, 24, 48, 96 and 120 (p<0.001, p=0.007, p=0.002, p=0.02 and p=0.01, respectively) in PPMS and at Weeks 12 and 24 (p<0.001 for both) in RMS were associated with PBVC.

Lower baseline NfL levels and treatment with ocrelizumab were both associated with lesser BV loss in PPMS and RMS independent of measures of disease severity.