[Hematological side effects of natalizumab: Correlation with clinical outcome]

Natalizumab (NTZ) is a monoclonal antibody used in a single-drug regimen to treat active relapsing remitting multiple sclerosis. Safety data collected during the AFFIRM pivotal study and post marketing cohorts reported infusion-related and allergic reactions, with development of persistent anti-NTZ antibodies in 6% of patients. Occurrence of hematological side effects (HSE), such as hyperlymphocytosis (HL) and hypereosinophilia (HEo) have been described. To our knowledge, there is no study assessing neither incidence of HSE, nor their correlation with clinical outcome. The objective is to evaluate prospectively the incidence of HSE of NTZ and to search for correlations with clinical outcome.

Clinical (EDSS, relapse, tolerance) and biological assessments were performed before the first infusion and every month during the follow-up in all patients treated with NTZ between 2007 and 2010. Before starting NTZ, data were collected on prior history of allergy and previous disease-modifying treatments (DMT). Statistical analysis was performed to search for correlations between the occurrence of HSE and clinical outcome.

The series included 66 patients (sex ratio: 1/2.8) followed for up to 17 months. Mean age was 39 (±SD) years. Mean EDSS score was 3.2 (±SD). Fifty-six percent of patients had DMT history with beta interferons (41%), glatiramer acetate (6%) and immunosuppressive drugs (cyclophosphamide, mitoxantrone) (9%). Annualized relapse rate during follow-up was 0.41. Infusion-related reactions were noted in 10% of patients. Two patients had allergic reactions and had stopped their infusions. HL developed in 48% of patients and HEo in 20%. Regarding age and medical or therapeutic history, no predictive factor of HSE occurrence could be identified. Incidence of infusion-related side effects was higher in patients with HEo (38%) in comparison with patients without HEo (3.8%). Relapse rate during NTZ treatment was not significantly different between the different groups.

This is the first prospective study assessing of HSE during NTZ treatment. There is a higher occurrence of intolerance reactions in patients with HEo.