title: Natalizumab reduces visual loss in patients with relapsing multiple sclerosis.
abstract: OBJECTIVE
  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).
  
  
  METHODS
  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%).
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA. lbalcer@mail.med.upenn.edu
authors: L J
authors: LJ
authors: Balcer
authors: S L
authors: SL
authors: Galetta
authors: P A
authors: PA
authors: Calabresi
authors: C
authors: C
authors: Confavreux
authors: G
authors: G
authors: Giovannoni
authors: E
authors: E
authors: Havrdova
authors: M
authors: M
authors: Hutchinson
authors: L
authors: L
authors: Kappos
authors: F D
authors: FD
authors: Lublin
authors: D H
authors: DH
authors: Miller
authors: P W
authors: PW
authors: O'Connor
authors: J T
authors: JT
authors: Phillips
authors: C H
authors: CH
authors: Polman
authors: E-W
authors: EW
authors: Radue
authors: R A
authors: RA
authors: Rudick
authors: W H
authors: WH
authors: Stuart
authors: A
authors: A
authors: Wajgt
authors: B
authors: B
authors: Weinstock-Guttman
authors: D R
authors: DR
authors: Wynn
authors: F
authors: F
authors: Lynn
authors: M A
authors: MA
authors: Panzara
mesh_terms: D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D001921:Brain / Q000187:drug effects / Q000276:immunology / Q000503:physiopathology; D015350:Contrast Sensitivity / Q000187:drug effects / Q000502:physiology; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000150:complications* / Q000188:drug therapy*; D000069442:Natalizumab; D009460:Neurologic Examination / Q000379:methods; D010919:Placebos; D011237:Predictive Value of Tests; D016896:Treatment Outcome; D014787:Vision Tests / Q000379:methods; D015354:Vision, Low / Q000188:drug therapy* / Q000209:etiology*; D014792:Visual Acuity / Q000187:drug effects; D014795:Visual Pathways / Q000187:drug effects / Q000276:immunology / Q000503:physiopathology
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007166:Immunosuppressive Agents; D000069442:Natalizumab; D010919:Placebos