Natalizumab reduces visual loss in patients with relapsing multiple sclerosis

被引:101
作者
Balcer, L. J.
Galetta, S. L.
Calabresi, P. A.
Confavreux, C.
Giovannoni, G.
Havrdova, E.
Hutchinson, M.
Kappos, L.
Lublin, F. D.
Miller, D. H.
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.
Panzara, M. A.
机构
[1] Univ Penn, Sch Med, Dept Neurol, Philadelphia, PA 19104 USA
[2] Univ Penn, Sch Med, Dept Ophthalmol, Philadelphia, PA 19104 USA
[3] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA
[4] Hop Neurol, Lyon, France
[5] Inst Neurol, London WC1N 3BG, England
[6] Gen Teaching Hosp, Prague, Czech Republic
[7] St Vincents Univ Hosp, Dublin, Ireland
[8] Univ Basel Hosp, Basel, Switzerland
[9] Mt Sinai Sch Med, New York, NY USA
[10] St Michaels Hosp, Toronto, ON M5B 1W8, Canada
[11] Multiple Sclerosis Ctr Texas Neurol, Dallas, TX USA
[12] Vrije Univ Amsterdam, Med Ctr, Amsterdam, Netherlands
[13] Cleveland Clin Fdn, Mellen Ctr Multiple Sclerosis Res, Cleveland, OH 44195 USA
[14] MS Ctr Atlanta, Atlanta, GA USA
[15] Silesian Med Univ, Katowice, Poland
[16] SUNY Buffalo, Baird Multiple Sclerosis Ctr, Buffalo, NY 14260 USA
[17] Biogen Idec Inc, Cambridge, MA USA
[18] Multiple Sclerosis Ctr, Northbrook, IL USA
关键词
D O I
10.1212/01.wnl.0000259521.14704.a8
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
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.
引用
收藏
页码:1299 / 1304
页数:6
相关论文
共 36 条
  • [1] [Anonymous], 2000, COMPLICATIONS AGE RE
  • [2] Azen SP, 2002, INVEST OPHTH VIS SCI, V43, P1742
  • [3] Low-contrast letter acuity testing captures visual dysfunction in patients with multiple sclerosis
    Baier, ML
    Cutter, GR
    Rudick, RA
    Miller, D
    Cohen, JA
    Weinstock-Guttman, W
    Mass, M
    Balcer, LJ
    [J]. NEUROLOGY, 2005, 64 (06) : 992 - 995
  • [4] Optic neuritis
    Balcer, LJ
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 2006, 354 (12) : 1273 - 1280
  • [5] New low-contrast vision charts: reliability and test characteristics in patients with multiple sclerosis
    Balcer, LJ
    Baier, ML
    Pelak, VS
    Fox, RJ
    Shuwairi, S
    Galetta, SL
    Cutter, GR
    Maguire, MG
    [J]. MULTIPLE SCLEROSIS JOURNAL, 2000, 6 (03) : 163 - 171
  • [6] Contrast letter acuity as a visual component for the Multiple Sclerosis Functional Composite
    Balcer, LJ
    Baier, ML
    Cohen, JA
    Kooijmans, MF
    Sandrock, AW
    Nano-Schiavi, ML
    Pfohl, DC
    Mills, M
    Bowen, J
    Ford, C
    Heidenreich, FR
    Jacobs, DA
    Markowitz, CE
    Stuart, WH
    Ying, GS
    Galetta, SL
    Maguire, MG
    Cutter, GR
    [J]. NEUROLOGY, 2003, 61 (10) : 1367 - 1373
  • [7] BALCER LJ, 2005, WALSH HOYTS CLIN NEU, V3, P3429
  • [8] A RANDOMIZED, CONTROLLED TRIAL OF CORTICOSTEROIDS IN THE TREATMENT OF ACUTE OPTIC NEURITIS
    BECK, RW
    CLEARY, PA
    ANDERSON, MM
    KELTNER, JL
    SHULTS, WT
    KAUFMAN, DI
    BUCKLEY, EG
    CORBETT, JJ
    KUPERSMITH, MJ
    MILLER, NR
    SAVINO, PJ
    GUY, JR
    TROBE, JD
    MCCRARY, JA
    SMITH, CH
    CHROUSOS, GA
    THOMPSON, HS
    KATZ, BJ
    BRODSKY, MC
    GOODWIN, JA
    ATWELL, CW
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 1992, 326 (09) : 581 - 588
  • [9] BECK RW, 1993, OPHTHALMOLOGY, V100, P691
  • [10] Development of a multiple sclerosis functional composite as a clinical trial outcome measure
    Cutter, GR
    Baier, ML
    Rudick, RA
    Cookfair, DL
    Fischer, JS
    Petkau, J
    Syndulko, K
    Weinshenker, BG
    Antel, JP
    Confavreux, C
    Ellison, GW
    Lublin, F
    Miller, AE
    Rao, SM
    Reingold, S
    Thompson, A
    Willoughby, E
    [J]. BRAIN, 1999, 122 : 871 - 882