Long-term safety evaluation of natalizumab for the treatment of multiple sclerosis

Introduction: Natalizumab is a humanized monoclonal antibody highly effective in relapsing-remittingmultiple sclerosis (MS). Important concerns about its safety have been pointed out mainly because ofthe risk of progressive multifocal leukoencephalopathy (PML), caused by the opportunistic John-Cunningham virus (JCV).Areas covered: This review analyzes all the safety aspects related to the use and safety of natalizumabin MS patients. Other than PML, post-marketing, safety red-flags have been reported, as liver orhaematological serious adverse events. Pregnancy evidences will be pointed out.The risk of PML depends on: concomitant or previous immunosuppression, exposure duration, anti–JCVantibody level. In natalizumab-related PML the average survival is 77%; prognostic features andinformation for the earliest identification of PML have been identified to maximally reduce its incidence,mortality and morbidity.Expert opinion: Natalizumab is a highly effective drug for MS patients but its safety issues represent arelevant limitation and impose strict clinical surveillance of treated patients. Some post-marketingsafety red-flags have been pointed out, with higher attention to severe liver failures and limphomacases. If PML and its consequences are considered the most relevant issues, a continuous surveillancemust be maintained also regarding other possible SAEs like liver diseases and malignancies.