Immune cells after prolonged Natalizumab therapy: implications for effectiveness and safety

Authors


S. Marousi, Department of Neurology, ‘G. Gennimatas’ General Hospital of Athens, 154 Mesogeion Ave, 15669, Athens, Greece

Tel.: 0030 6972009400

Fax: 0030 2107470468

e-mail: smarousi@upatras.gr

Abstract

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 CD4+, CD8+ and NK T-cells (P = 0.011). CD4/CD8 ratio was significantly decreased in NAT-MS patients (P = 0.018) and showed no correlation with the number of NAT doses. The reduced CD4/CD8 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 CD4/CD8 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 CD4/CD8 ratio as a possible contributor to the recently developed risk stratification scheme for PML.

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