BERLIN—Serum neurofilament light chain (sNfL) levels are clinically relevant, and data suggest cut points to enable disease severity stratification and treatment monitoring in patients with relapsing-remitting multiple sclerosis (MS), according to research described at ECTRIMS 2018.
Various investigations have indicated that sNfL is associated with disease activity and predicts long-term clinical and imaging outcomes in patients with relapsing-remitting MS. Disease-modifying treatments (DMTs) reduce sNfL levels in these patients. “The integration of sNfL into clinical practice will require a standardized, validated assay and defined, clinically meaningful cut points validated with real-world data,” said Peter Calabresi, MD, Director of the Division of Neuroimmunology at Johns Hopkins Medicine in Baltimore, and colleagues.
Dr. Calabresi and colleagues conducted a study to define the sNfL levels relevant to disease severity stratification and treatment monitoring in patients with relapsing-remitting MS using samples and data from phase III clinical studies supported by Biogen. They measured sNfL with a single-molecule array Advantage kit or laboratory method in serial samples from more than 1,000 patients enrolled in four studies.
In the ADVANCE trial (which examined peginterferon beta-1a in 594 patients with relapsing-remitting MS), sNfL was measured at baseline, every three months until Year 2, and then every six months until Year 4. In the CHAMPS trial (which analyzed interferon beta 1a in 319 patients with clinically isolated syndrome), sNfL was measured at baseline and Week 48. In the MSCRG study (which examined interferon beta 1a in 164 patients with relapsing-remitting MS), sNfL was measured at Years 3 and 4. In SENTINEL (which examined natalizumab in 122 patients with relapsing-remitting MS), sNfL was measured at baseline and Week 96. Statistical analyses included Spearman correlation, analysis of variance, chi-squared test, Kaplan-Meier analysis, and multivariate logistic regression.
Baseline sNfL levels were associated with the number of enhancing lesions and accumulation of new T2 lesions over time. Patients with no evident disease activity had consistently low sNfL levels, but those with active disease, especially with high brain atrophy rates, had elevated sNfL levels. Dr. Calabresi’s group found that an sNfL level greater than 16 pg/mL indicated a high probability of disease activity over the following year (positive predictive values of 92% and 95% in test and verification cohorts, respectively). Using the average of sNfL levels at baseline and Months 3 and 6 further improved the positive predictive value. Similarly, an sNfL level greater than 16 pg/mL was associated long-term with worse clinical and imaging outcomes, including progression of Expanded Disability Status Scale score (12 years), increase in T2 lesion volume (10 years), and brain atrophy (five years). DMTs lowered sNfL levels. Natalizumab reduced sNfL below 16 pg/mL in 96% of patients.
The study was sponsored by Biogen.