Natalizumab plus interferon beta-1a for relapsing multiple sclerosis

被引:996
作者
Rudick, RA [1 ]
Stuart, WH
Calabresi, PA
Confavreux, C
Galetta, SL
Radue, EW
Lublin, FD
Weinstock-Guttman, B
Wynn, DR
Lynn, F
Panzara, MA
Sandrock, AW
Fazekas, F
Enzinger, C
Seifert, T
Storch, M
Strasser-Fuchs, S
Berger, T
Dilitz, E
Egg, R
Deisenhammer, F
Decoo, D
Lampaert, J
Bartholome, E
Bier, J
Stenager, E
Rasmussen, M
Binzer, M
Shorsh, K
Christensen, M
Ravnborg, M
Sorensen, PS
Blinkenberg, M
Petersen, B
Hansen, HJ
Bech, E
Petersen, T
Kirkegaard, M
Eralinna, J
Ruutiainen, J
Soilu-Hänninen, M
Säkö, E
Laaksonen, M
Reunanen, M
Remes, A
Keskinarkaus, I
Moreau, T
Noblet, M
Rouaud, O
Couvreur, G
机构
[1] Cleveland Clin Fdn, Mellen Ctr Multiple Sclerosis Treatment & Res, 9500 Euclid Ave, Cleveland, OH 44195 USA
[2] MS Ctr Atlanta, Atlanta, GA USA
[3] Johns Hopkins Multiple Sclerosis Ctr, Baltimore, MD USA
[4] Hop Neurol, Lyon, France
[5] Univ Penn, Sch Med, Philadelphia, PA 19104 USA
[6] Univ Basel Hosp, CH-4031 Basel, Switzerland
[7] Mt Sinai Sch Med, New York, NY USA
[8] SUNY Buffalo, Buffalo, NY USA
[9] Multiple Sclerosis Ctr, Northbrook, IL USA
[10] Biogen Idec Inc, Cambridge, MA USA
[11] Univ Klin Neurol, Graz, Austria
[12] Univ Klin Neurol, Innsbruck, Austria
[13] Elizabeth Ziekenhuis, Sijsele, Belgium
[14] Erasme Univ Hosp, Brussels, Belgium
[15] Scleroseklinik, Sydvestjysk Sygehus, Esbjerg, Denmark
[16] Scleroseklinik, Rigshosp, Copenhagen, Denmark
[17] Aarhus Hosp, Scleroseklinik, Neurologisk Afdeling F, Aarhus, Denmark
[18] Finnish Special Neurol Ctr, Turku, Finland
[19] Oulu Univ Hosp, Oulu, Finland
[20] Ctr Hosp Univ, Dijon, France
[21] Ctr Hosp Univ, Rennes, France
[22] Hop Rothschild, Paris, France
[23] Hop B Roger Salengro, Lille, France
[24] Ctr Hosp, Nancy, France
[25] Hop Adultes Timone, Marseille, France
[26] Hop La Pitie Salpetriere, Paris, France
[27] Hop Gabriel Montpied, Clermont Ferrand, France
[28] Hop Henri Mondor, Creteil, France
[29] Hop Jean Minjoz, Besancon, France
[30] Hop Neurol, Lyon, France
[31] Hop Pellegrin, Bordeaux, France
[32] Asklepios Klin Schildautal, Seesen, Germany
[33] Asklepios Klin Schildautal, Harz, Germany
[34] Deutsch Klin Diagnost, Wiesbaden, Germany
[35] Univ Dusseldorf, Dusseldorf, Germany
[36] Henrietten Stiftung Hannover, Hannover, Germany
[37] Inst Klin Neuroimmunol, Munich, Germany
[38] Judisches Krakenhaus, Berlin, Germany
[39] Kamillus Klin, Asbach, Germany
[40] Neurol Klin & Poliklin, Rostock, Germany
[41] Univ Regensburg, Neurol Klin & Poliklin, Regensburg, Germany
[42] Krankenhaus Hennigsdorf, Hennigsdorf, Germany
[43] Neurol Klin & Poliklin, Wurzburg, Germany
[44] Univ Klinikum Essen, Essen, Germany
[45] Stadtische Klin Osnabruck, Osnabruck, Germany
[46] Univ Giessen Klinikum, Giessen, Germany
[47] Hadassah Univ Hosp Ein Kerem, Jerusalem, Israel
[48] MS Ctr, Tel Hashomer, Israel
[49] Univ Roma La Sapienza, Policlin Umberto I, Rome, Italy
[50] Azienda Osped Padova, Clin Neurol 1, Padua, Italy
关键词
D O I
10.1056/NEJMoa044396
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background: Interferon beta is used to modify the course of relapsing multiple sclerosis. Despite interferon beta therapy, many patients have relapses. Natalizumab, an (alpha)(sub 4) integrin antagonist, appeared to be safe and effective alone and when added to interferon beta-1a in preliminary studies. Methods: We randomly assigned 1171 patients who, despite interferon beta-1a therapy, had had at least one relapse during the 12-month period before randomization to receive continued interferon beta-1a in combination with 300 mg of natalizumab (589 patients) or placebo (582 patients) intravenously every 4 weeks for up to 116 weeks. The primary end points were the rate of clinical relapse at 1 year and the cumulative probability of disability progression sustained for 12 weeks, as measured by the Expanded Disability Status Scale, at 2 years. Results: Combination therapy resulted in a 24 percent reduction in the relative risk of sustained disability progression (hazard ratio, 0.76; 95 percent confidence interval, 0.61 to 0.96; P=0.02). Kaplan-Meier estimates of the cumulative probability of progression at two years were 23 percent with combination therapy and 29 percent with interferon beta-1a alone. Combination therapy was associated with a lower annualized rate of relapse over a two-year period than was interferon beta-1a alone (0.34 vs. 0.75, P<0.001) and with fewer new or enlarging lesions on T(sub 2)-weighted magnetic resonance imaging (0.9 vs. 5.4, P<0.001). Adverse events associated with combination therapy were anxiety, pharyngitis, sinus congestion, and peripheral edema. Two cases of progressive multifocal leukoencephalopathy, one of which was fatal, were diagnosed in natalizumab-treated patients. Conclusions: Natalizumab added to interferon beta-1a was significantly more effective than interferon beta-1a alone in patients with relapsing multiple sclerosis. Additional research is needed to elucidate the benefits and risks of this combination treatment.
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收藏
页码:911 / 923
页数:13
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