The systematic search was performed according to the PRISMA guidelines and included databases containing studies comparing EID (5-12 weeks) to SID (4 weeks) of natalizumab in MS patients. Relapse, disability progression (with the EDSS), radiological activity (Gadolinium-enhancing and T2 lesions) and PML data were mined. The possibility of bias was evaluated with the help of the ROB 2 and ROBINS-I tools. Random- or fixed-effects models were used to conduct meta-analyses based on the heterogeneity (I² statistic), and the results were presented in the form of risk ratios (RR) or mean differences (MD). 

Twenty-five studies were included. Disability progression (MD -0.09, 95% CI: -0.46 to 0.29), PML incidence (RR 1.03, 95% CI: 0.29 to 3.60), and the risk of new T2 lesions (RR 1.24, 95% CI: 0.96 to 1.61) did not have significant differences between EID and SID. EID was linked with statistically significant decrease in risk of clinical relapse (RR 0.91, 95% CI: 0.83 to 1.00). Subgroup analysis demonstrated that shorter EID periods (5-8 weeks) have superior radiological control in comparison with longer ones (>8 weeks), which shows that efficacy is interval-dependent. 

EID natalizumab has the same efficacy and safety profile as SID with the possibility for reduced risk relapse. 6-week dosing interval might have an optimal balance between efficacy-safety.