Immune cells after prolonged N atalizumab therapy: implications for effectiveness and safety

Background Previous studies on Natalizumab ( NAT ) have shown increased circulation of most white blood cells ( WBC ) in multiple sclerosis ( MS ) patients shortly after its introduction. Aim To describe peripheral immune cell phenotypes after more than 2 years of continuous NAT therapy and test for associations with clinical response to therapy. Methods Peripheral immune cell subsets were analyzed in 44 NAT ‐ MS patients receiving NAT for over 24 months, and in 22 NAT ‐free control‐ MS patients. Results NAT ‐ MS patients displayed significantly higher numbers of all WBC when compared with controls. B lymphocytes exhibited a more pronounced increase when compared with CD 4+, CD 8+ and NK T‐cells ( P  = 0.011). CD 4/ CD 8 ratio was significantly decreased in NAT ‐ MS patients ( P  = 0.018) and showed no correlation with the number of NAT doses. The reduced CD 4/ CD 8 ratio was attributable to the ‘ EDSS improvement’ group only, irrespective of age, sex and disease severity. Conclusions The study suggests that there is no desensitization effect after prolonged NAT exposure. A reduced CD 4/ CD 8 ratio was associated with long‐term response to therapy; thus, those patients who most benefitted from the drug might be at greater risk for opportunistic infections like progressive multifocal leucoencephalopathy ( PML ). We provide implications for future research for the CD 4/ CD 8 ratio as a possible contributor to the recently developed risk stratification scheme for PML .