Natalizumab reduces visual loss in patients with relapsing multiple sclerosis.
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.
Balcer
L J
LJ
Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA. lbalcer@mail.med.upenn.edu
Galetta
S L
SL
Calabresi
P A
PA
Confavreux
C
C
Giovannoni
G
G
Havrdova
E
E
Hutchinson
M
M
Kappos
L
L
Lublin
F D
FD
Miller
D H
DH
O'Connor
P W
PW
Phillips
J T
JT
Polman
C H
CH
Radue
E-W
EW
Rudick
R A
RA
Stuart
W H
WH
Wajgt
A
A
Weinstock-Guttman
B
B
Wynn
D R
DR
Lynn
F
F
Panzara
M A
MA
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
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007166:Immunosuppressive Agents; D000069442:Natalizumab; D010919:Placebos