Natalizumab for the treatment of relapsing multiple sclerosis

Richard A Rudick, Michael A Panzara, Richard A Rudick, Michael A Panzara

Abstract

Natalizumab is an alpha4-integrin antagonist approved as monotherapy for patients with relapsing multiple sclerosis (MS), based on demonstrated efficacy in the pivotal AFFIRM study (N = 942). Natalizumab monotherapy reduced risk of disability progression by 42%-54% and annualized relapse rate by 68% during a period of 2 years. Natalizumab was also associated with significant reductions in number of T2-hyperintense, gadolinium-enhancing, and T1-hypointense lesions and in volume of T2-hyperintense lesions (all p < 0.001) on magnetic resonance imaging. Furthermore, natalizumab-treated patients in AFFIRM experienced significant improvements from baseline in the physical and mental components of the Short Form-36 (p </= 0.01) and a 35% reduction in risk of clinically significant vision loss (p = 0.008 vs placebo). Natalizumab was well tolerated in phase 3 studies. Common adverse events were generally mild and included headache, fatigue, urinary tract infections, and arthralgia. Serious adverse events were similar between treatment groups. The incidence of serious hypersensitivity reactions associated with natalizumab was <1%. Progressive multifocal leukoencephalopathy was a rare complication of treatment, observed in 2 patients with MS who received natalizumab plus interferon beta-1a. The robust clinical benefits of natalizumab, including benefits on patient-reported quality of life, make it an important addition to disease-modifying therapies available to patients with relapsing MS.

Keywords: multiple sclerosis; natalizumab; α4-integrin antagonist.

Figures

Figure 1
Figure 1
Mean changes from baseline in Physical Component Summary (PCS) and Mental Component Summary (MCS) scores of the Short Form-36 in patients from the AFFIRM study. Reprinted from Rudick RA, Miller D, Hass S, et al. 2007. Health-related quality of life in multiple sclerosis: effects of natalizumab. Ann Neurol, 62:335–46. Copyright © 2007 (American Neurological Association), with permission of John Wiley & sons, Inc.
Figure 2
Figure 2
Kaplan-Meier plots of the time to sustained worsening of vision scores from baseline during the AFFIRM study. The cumulative probability of sustained worsening of visual function was defined as 2-line (10-letter) reductions in Sloan chart scores persisting over 12 weeks. Reprinted from Balcer LJ, Galetta SL, Calabresi PA, et al. 2007. Natalizumab reduces visual loss in patients with relapsing multiple sclerosis. Neurology, 68:1299–304. Copyright © 2007, with permission from Lippincott, Williams & Wilkins.
Figure 3
Figure 3
Cumulative probability of infection in the AFFIRM study (unpublished data on file, Biogen Idec).
Figure 4
Figure 4
Diagnostic algorithm for patients with suspected progressive multifocal leukoencephalopathy (PML). Reprinted from Kappos L, Bates D, Hartung H-P, et al. 2007. Natalizumab treatment for multiple sclerosis: recommendations for patient selection and monitoring. Lancet Neurol, 6:431–41. Copyright © 2007, with permission from Elsevier. aIf PML is suspected on the basis of clinical presentation and MRI is not readily available, CSF assessment to exclude PML should be considered before MRI. Abbreviations: CSF, cerebrospinal fluid; JCV, polyomavirus JC virus; MRI, magnetic resonance imaging; MS, multiple sclerosis; PML, progressive multifocal leukoencephalopathy.

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