Use of natalizumab in multiple sclerosis: current perspectives

ABSTRACT

Introduction: Natalizumab is an efficacious monoclonal antibody approved for use in relapsing-remitting multiple sclerosis (RRMS). Multiple studies have demonstrated reduced relapse rate, decreased disability progression and prolonged disease-free intervals with natalizumab use. However, natalizumab is associated with an increased risk of progressive multifocal leukoencephalopathy (PML), thus restricting its widespread use with populations at high risk for developing PML. Recently, the effect of natalizumab in secondary-progressive (SPMS) population has been explored.

Areas covered: This review highlights the pathophysiology behind disease progression in MS and summarizes various attributes of natalizumab including: its pharmacological properties and global economic impact, results of clinical efficacy studies, its role in SPMS, pregnancy and its adverse events profile including PML and discontinuation protocols.

Expert opinion: Despite an established role in reducing RRMS disease activity, natalizumab has found limited use in SPMS due to insufficient evidence of efficacy. Current disease-modifying therapies exert modest overall benefit in SPMS owing to its complex pathophysiology, higher prevalence of comorbidities and increased PML risk with age and lack of reliable outcome measures. Finding more appropriate MRI and clinical outcome measures is quintessential for designing future randomized trials and possibly exploring primary neuroprotective agents for treating SPMS.

KEYWORDS:

• Multiple sclerosis
• natalizumab
• MRI
• disability progression
• relapse rate
• brain atrophy
• progressive multifocal leukoencephalopathy
• monoclonal antibodies

Acknowledgments

Biogen Idec reviewed and provided feedback on the paper. The authors had full editorial control of the paper, and provided their final approval of all content.

Declaration of interest

D Hojnacki has received speaker honoraria and consultant fees from Biogen Idec, Teva Pharmaceutical Industries Ltd, EMD Serono, Pfizer Inc. and Novartis. C Kolb has received speaker honoraria from Novartis, Genzyme and Biogen Idec. B Weinstock-Guttman has received honoraria as a speaker and a consultant for Biogen Idec, Teva Pharmaceuticals, EMD Serono, Genzyme and Sanofi, Novartis and Acorda. Dr Weinstock-Guttman has also received research funds from Biogen Idec, Teva Pharmaceuticals, EMD Serono, Genzyme and Sanofi, Novartis and Acorda. R Zivadinov received personal compensation from Biogen Idec, Teva Pharmaceuticals, EMD Serono, Novartis, Claret Medical and Genzyme for speaker and consultant fees. Dr Zivadinov has also received financial support for research activities from Biogen Idec, Teva Pharmaceuticals, EMD Serono, Novartis, Claret Medical and Genzyme. Dr Zivadinov is also the treasurer of the International Society for Neurovascular Disease. 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.