The role of natalizumab in the treatment of multiple sclerosis: benefits and risks. (September 2017)

• Record Type: Journal Article
• Authors: Singer, Barry A.
• Is Part Of: Therapeutic advances in neurological disorders. Volume 10:Number 9(2017)
• Page Start: 327
• Page End: 336
• Publication Date: 2017-09
• Subjects: multiple sclerosis -- natalizumab -- progressive multifocal leukoencephalopathy; Nervous system -- Diseases -- Periodicals; Nervous system -- Degeneration -- Periodicals; Nervous system -- Diseases -- Treatment -- Periodicals; Nervous System Diseases -- therapy -- Periodicals; Neurodegenerative Diseases -- Periodicals; Système nerveux -- Maladies -- Périodiques; Système nerveux -- Dégénérescence -- Périodiques; Système nerveux; Système nerveux -- Maladies -- Traitement -- Périodiques; 616.805
• DOI: 10.1177/1756285617716002
• Languages: English
• ISSNs: 1756-2856

Abstract

Natalizumab, a monoclonal antibody that blocks lymphocyte infiltration in the central nervous system, is a valuable tool in the treatment of relapsing forms of multiple sclerosis (MS). In a phase III clinical trial comparing natalizumab with placebo over 2 years, natalizumab reduced annualized relapse rate by 68%, 12-week confirmed disability progression by 42%, and reduced contrast-enhancing lesions by 92%. In post hoc analyses, natalizumab treatment was associated with 37% of patients achieving no evidence of disease activity ( versus 7% on placebo) and 30% achieving sustained disability improvement ( versus 19% on placebo). Natalizumab did not achieve a statistically significant primary composite disability outcome in a trial of 887 patients with secondary progressive MS, but it did demonstrate a benefit on a prespecified component of the 9-Hole Peg Test. The greatest risk of natalizumab treatment is progressive multifocal leukoencephalopathy (PML), with a 23% mortality rate. Risk stratification on the basis of immunosuppressant exposure, natalizumab treatment duration and anti-John Cunningham virus (JCV) antibody status and index has greatly improved clinical decision making. Other potential serious natalizumab-associated risks reported in clinical trials and postmarketing settings include infusion reactions, hepatotoxicity and rare, serious opportunistic infections. With more than a decade of continuous postmarketing experience, natalizumab remains a very effective option for patients with relapsing forms of MS. To optimize appropriate selection of natalizumab for patients with relapsing MS, however, a thorough understanding of individual patient risk factors for PML or other adverse events is also required.