Serum neurofilament light chain (sNfL) levels are associated with disease activity and prognosis in relapsing-remitting multiple sclerosis (RRMS) patients. Treatment with second-line disease modifying therapies (DMTs) leads to a reduction of sNfL, but little is known regarding first-line DMTs as dimethyl fumarate (DMF).
To explore changes of sNfL levels in RRMS patients during treatment with DMF. To evaluate the potential role of sNfL measurement to predict an optimal treatment response.
Blood samples from 64 consecutive RRMS patients initiating DMF at Hospital Universitario Ramón y Cajal were collected at baseline and at 3, 6 and 12 months thereafter. sNfL levels were measured using a sensitive Single Molecular Array (SIMOA) assay (Quanterix). Patients were classified into No Evidence of Disease Activity (NEDA) and Ongoing Disease Activity (ODA) according the presence/absence of relapses, EDSS progression and/or MRI activity during the first year.
Age at treatment initiation was 40.6 [33.2-46.3] years (median [25-75%IQR]) and EDSS was 1.5 [1.5-2.5]. Forty eight (75%) patients received other previous DMTs, seven of them were second-line DMTs. 66% of patients had evidence of disease activity at DMF initiation. Baseline sNfL levels were higher in patients who had evidence of disease activity at that time compared with patients who had not (12.2 pg/ml Vs. 8.8 pg/ml, p=0.024). No differences were found in baseline sNfL levels between naïve and previously treated patients, or between patients treated with first and second line DMTs. After 12 months of DMF treatment, 44 (69%) patients were NEDA and 20 (31%) were ODA. Baseline sNfL levels were higher in ODA patients compared to NEDA patients (14.6 pg/ml Vs. 9.2 pg/ml, p=0.016). A cut-off value of 12 pg/ml was established to predict NEDA status (OR=4.7; 95%CI: 1.6–15.7; p=0.008). After one year of DMF, sNfL levels decreased by 34.4% (p<0.0001). Both NEDA and ODA patients experienced a progressive sNfL reduction during the first year of treatment. However, this reduction was observed earlier in NEDA patients (three months after DMF initiation) than in ODA patients (six months).
DMF induced a progressive decrease in sNfL concentration during the first year of treatment. This reduction was delayed in ODA patients. Patients with basal sNFL values ≤ 12 pg/ml showed increased probability to achieve NEDA status at 12 months.