Natalizumab reduces visual loss in patients with relapsing multiple sclerosis

• Published in: Neurology Vol. 68; no. 16; pp. 1299 - 1304
• Main Authors: BALCER, L. J, GALETTA, S. L, O'CONNOR, P. W, PHILLIPS, J. T, POLMAN, C. H, RADUE, E.-W, RUDICK, R. A, STUART, W. H, WAJGT, A, WEINSTOCK-GUTTMAN, B, WYNN, D. R, LYNN, F, CALABRESI, P. A, PANZARA, M. A, CONFAVREUX, C, GIOVANNONI, G, HAVRDOVA, E, HUTCHINSON, M, KAPPOS, L, LUBLIN, F. D, MILLER, D. H
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 17-04-2007
• Subjects: Adolescent; Adult; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - adverse effects; Antibodies, Monoclonal, Humanized; Biological and medical sciences; Brain - drug effects; Brain - immunology; Brain - physiopathology; Contrast Sensitivity - drug effects; Contrast Sensitivity - physiology; Double-Blind Method; Female; Humans; Immunomodulators; Immunosuppressive Agents - administration & dosage; Immunosuppressive Agents - adverse effects; Kaplan-Meier Estimate; Male; Medical sciences; Middle Aged; Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis; Multiple Sclerosis, Relapsing-Remitting - complications; Multiple Sclerosis, Relapsing-Remitting - drug therapy; Natalizumab; Neurologic Examination - methods; Neurology; Pharmacology. Drug treatments; Placebos; Predictive Value of Tests; Treatment Outcome; Vision Tests - methods; Vision, Low - drug therapy; Vision, Low - etiology; Visual Acuity - drug effects; Visual Pathways - drug effects; Visual Pathways - immunology; Visual Pathways - physiopathology; Human; Eye disease; Multiple sclerosis; Nervous system diseases; Natalizumab; Visual impairment; Vision disorder; Central nervous system disease; Blindness; Inflammatory disease
• ISSN: 0028-3878; 1526-632X
• DOI: 10.1212/01.wnl.0000259521.14704.a8

To examine the effects of natalizumab on low-contrast letter acuity as a prespecified tertiary endpoint in two randomized clinical trials and to evaluate the usefulness of low-contrast letter acuity testing as a candidate test of visual function in multiple sclerosis (MS).
AFFIRM and SENTINEL were randomized, double-blind, placebo-controlled, multicenter, phase 3 clinical trials of natalizumab in relapsing MS. Natalizumab was evaluated as monotherapy in AFFIRM and as add-on to interferon beta-1a in SENTINEL. Vision testing was performed at 100% contrast (visual acuity) and low-contrast (2.5% and 1.25%).
The risk of clinically significant visual loss (predefined as a two-line worsening of acuity sustained over 12 weeks) at the lowest contrast level (1.25%) was reduced in the natalizumab treatment arms by 35% in AFFIRM (hazard ratio = 0.65; 95% CI: 0.47 to 0.90; p = 0.008) and by 28% in SENTINEL (hazard ratio = 0.72; 95% CI: 0.54 to 0.98; p = 0.038, Cox proportional hazards models). Mean changes in vision scores from baseline were also significantly different, reflecting worsening in non-natalizumab groups.
Natalizumab reduces visual loss in patients with relapsing multiple sclerosis. Low-contrast acuity testing has the capacity to demonstrate treatment effects and is a strong candidate for assessment of visual outcomes in future multiple sclerosis trials.