Prognostic significance of neurofilament light in Fingolimod therapy for Multiple Sclerosis: A systemic review and meta-analysis based on randomized control trials

Objective: This research was conducted to assess Neurofilament light chain (NfL) as prognostic factor for Multiple Sclerosis and effect of Fingolimod on plasma levels of NfL.Materials and Methods: A systemic search was conducted from electronic databases (PubMed/Medline, Cochrane Library, and Google Scholar) from inception to 7th September 2022. All statistical analyses were conducted in Review Manager 5.4.1. Studies meeting inclusion criteria were selected. Only those studies that involved Multiple sclerosis patients in which plasma levels of NfL was provided and Fingolimod was used in the treatment group. Fixed-effect model was used to pool the studies to assess NfL as prognostic factor, which was reported in the Hazards ratio (HR) and their corresponding 95% confidence interval (CI). Moreover, effect of Fingolimod on NfL levels was analysed qualitatively.Results: Five Randomized Controlled Trials were used in the study. Four studies were used in quantitative analysis which showed increased NfL was related to significant increase in cognitive disability worsening (HR= 1.66 [1.35, 2.05]; p< 0.00001; I2= 0%). The qualitative analysis method was employed to evaluate the factors correlating with increased NfL levels in Multiple Sclerosis patients. Five studies evaluated that there was significant decrease in NfL levels when Fingolimod was used as compared to placebo. 4 studies were included to correlated NfL levels with clinical and MRI parameters and association was found between increasing NfL levels and relapses, active/new T2 lesions and percentage of brain volume change.Conclusion: The results of our meta-analysis and systematic review demonstrated statistically significant effect of NfL as a prognostic marker with its level being decreased significantly when Fingolimod was used for treating Multiple Sclerosis