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

ABSTRACT

Introduction: Natalizumab is a humanized monoclonal antibody highly effective in relapsing-remitting multiple sclerosis (MS). Important concerns about its safety have been pointed out mainly because of the 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 natalizumab in MS patients. Other than PML, post-marketing, safety red-flags have been reported, as liver or haematological serious adverse events. Pregnancy evidences will be pointed out.

The risk of PML depends on: concomitant or previous immunosuppression, exposure duration, anti–JCV antibody level. In natalizumab-related PML the average survival is 77%; prognostic features and information 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 a relevant limitation and impose strict clinical surveillance of treated patients. Some post-marketing safety red-flags have been pointed out, with higher attention to severe liver failures and limphoma cases. If PML and its consequences are considered the most relevant issues, a continuous surveillance must be maintained also regarding other possible SAEs like liver diseases and malignancies.

KEYWORDS:

• Multiple sclerosis
• natalizumab
• safety
• progressive multifocal leukoencephalopathy
• long-term safety
• adverse events
• serious adverse event
• John-Cunningham virus

Declaration of interest

M Clerico has received personal compensations for serving on advisory boards for Biogen and Merck, by Merck for editorial collaborations and has had travel expenses for congresses paid for by Merck, Biogen, Norvatis and Sanofi. SF De Mercanti has had travel expenses for congresses paid for by Merck, Biogen, Novartis and Sanofi. CA Artusi has had travel expenses for congresses paid for by Merck, Biogen, Norvatis and Sanofi . L Durelli has received personal compensations for serving on advisory boards for Sanofi and for editorial collaborations with Merck and has had travel expenses for congresses paid for by Merck, Biogen, Norvatis and Sanofi. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This paper has not been funded.