Oral Fingolimod or Intramuscular Interferon for Relapsing Multiple Sclerosis

被引:1691
作者
Cohen, Jeffrey A. [1 ]
Barkhof, Frederik [2 ]
Comi, Giancarlo [3 ]
Hartung, Hans-Peter [6 ]
Khatri, Bhupendra O. [8 ]
Montalban, Xavier [9 ]
Pelletier, Jean [11 ,12 ]
Capra, Ruggero [4 ]
Gallo, Paolo [5 ]
Izquierdo, Guillermo [10 ]
Tiel-Wilck, Klaus [7 ]
de Vera, Ana [13 ]
Jin, James [16 ]
Stites, Tracy [16 ]
Wu, Stacy [16 ]
Aradhye, Shreeram [16 ]
Kappos, Ludwig [14 ,15 ]
机构
[1] Cleveland Clin, Mellen Ctr, Cleveland, OH 44195 USA
[2] Vrije Univ Amsterdam, Med Ctr, Amsterdam, Netherlands
[3] Univ Vita & Salute, Hosp San Raffaele, Neurol Clin, Milan, Italy
[4] Presidio Osped Montichiari, Reg Multiple Sclerosis Ctr, Montichiari, Italy
[5] Univ Hosp Padua, Dept Neurosci, Multiple Sclerosis Ctr Veneto Reg, Padua, Italy
[6] Univ Dusseldorf, Dept Neurol, D-4000 Dusseldorf, Germany
[7] Klin Studienzentrum, Neurol Facharztzentrum Berlin, Berlin, Germany
[8] Reg MS Ctr, Ctr Neurol Disorders, Milwaukee, WI USA
[9] Hosp Gen Valle Hebron, Neuroimmunol Unit, Barcelona, Spain
[10] Hosp Univ Virgen Macarena, Serv Neurol, MS Unit, Seville, Spain
[11] CHU Timone, Dept Neurol, Marseille, France
[12] CHU Timone, Dept Res CRMBM, Marseille, France
[13] Novartis Pharmaceut, Basel, Switzerland
[14] Univ Basel Hosp, Dept Neurol, CH-4031 Basel, Switzerland
[15] Univ Basel Hosp, Dept Res, CH-4031 Basel, Switzerland
[16] Novartis Pharmaceut, E Hanover, NJ USA
关键词
EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; PHASE-II EXTENSION; RECEPTOR AGONISTS; LYMPHOCYTE EGRESS; FTY720; BETA-1A; ORGANS; MS;
D O I
10.1056/NEJMoa0907839
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
BACKGROUND Fingolimod (FTY720), a sphingosine-1-phosphate-receptor modulator that prevents lymphocyte egress from lymph nodes, showed clinical efficacy and improvement on imaging in a phase 2 study involving patients with multiple sclerosis. METHODS In this 12-month, double-blind, double-dummy study, we randomly assigned 1292 patients with relapsing-remitting multiple sclerosis who had a recent history of at least one relapse to receive either oral fingolimod at a daily dose of either 1.25 or 0.5 mg or intramuscular interferon beta-1a ( an established therapy for multiple sclerosis) at a weekly dose of 30 mu g. The primary end point was the annualized relapse rate. Key secondary end points were the number of new or enlarged lesions on T-2-weighted magnetic resonance imaging (MRI) scans at 12 months and progression of disability that was sustained for at least 3 months. RESULTS A total of 1153 patients (89%) completed the study. The annualized relapse rate was significantly lower in both groups receiving fingolimod -0.20 (95% confidence interval [CI], 0.16 to 0.26) in the 1.25-mg group and 0.16 ( 95% CI, 0.12 to 0.21) in the 0.5-mg group - than in the interferon group (0.33; 95% CI, 0.26 to 0.42; P<0.001 for both comparisons). MRI findings supported the primary results. No significant differences were seen among the study groups with respect to progression of disability. Two fatal infections occurred in the group that received the 1.25-mg dose of fingolimod: disseminated primary varicella zoster and herpes simplex encephalitis. Other adverse events among patients receiving fingolimod were nonfatal herpesvirus infections, bradycardia and atrioventricular block, hypertension, macular edema, skin cancer, and elevated liver-enzyme levels. CONCLUSIONS This trial showed the superior efficacy of oral fingolimod with respect to relapse rates and MRI outcomes in patients with multiple sclerosis, as compared with intramuscular interferon beta-1a. Longer studies are needed to assess the safety and efficacy of treatment beyond 1 year.
引用
收藏
页码:402 / 415
页数:14
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