文摘
摘要目的:评估是否fingolimod(0.5毫克和0.25毫克)卓越的功效比glatiramer醋酸(GA)在减少疾病活动20毫克/ 12个月复发缓和多发性硬化患者。
背景:Fingolimod 0.5毫克的疗效已经证明在安慰剂组和干扰素β-1a第三阶段试验。肉搏战疾病修饰治疗的有效性和安全性的比较重要的通知治疗决定在临床实践中。
设计/方法:在评估阶段3 b、随机、多中心、评定等级,dose-blinded学习,符合条件的患者被随机分配接受每天换一次口服fingolimod 0.5毫克(N = 352), 0.25毫克(N = 370),或皮下GA 20毫克(N = 342)。优势的fingolimod剂量测试等级:0.5毫克和GA 0.25毫克和GA紧随其后。主要终点是减少复发年率(ARR)和二级端点在12个月内MRI疾病活动的措施。安全性和耐受性进行了评估。
结果:总体而言,859名(80.7%)患者完成了研究。超过12个月,arr fingolimod 0.5毫克和GA分别为0.153和0.258,分别(相对减少(RR), 40.7%;p = 0.0138);fingolimod 0.25毫克的数值RR 14.6%但没有达到统计学意义。GA相比,fingolimod 0.5毫克和0.25毫克显著降低新/新扩大的T2的平均数(RR,分别为54.4%和42.1%;p < 0.0001)和钆增强T1病变(RR, 55.6%剂量;分别为p = 0.0167, p = 0.0011)。不良事件报告(AEs)与fingolimod剂量符合已知的安全性。更多停用研究药物与GA报道由于injection-related AEs,同意撤军,治疗效果不满意。
结论:Fingolimod 0.5毫克的最佳有效剂量,第一个也是唯一一个疾病修饰治疗在减少疾病活动方面表现出优越的功效和GA在一对一的控制研究。安全的结果与既定fingolimod的安全性。
披露:克里族博士已经收到个人赔偿咨询、担任科学顾问委员会说,从Abbvie或其他活动,Akili,生原体,EMD Serono GeNeuro和诺华。高盛已收到个人赔偿咨询博士担任科学顾问委员会,说,与EMD Serono或其他活动,Celgene公司,赛诺菲安万特Genzyme,诺华制药、RxMx, Teva神经科学。高盛已收到MedDay研究支持博士,诺华,NIH,国家社会,女士和PCORI。Corboy博士已经收到个人赔偿咨询、担任科学顾问委员会说,'芝加哥商品交易所或其他活动,Mylan,诺华。Corboy博士已经收到个人薪酬在一篇社论中编辑的能力,神经学:临床实践。首页Corboy博士已经收到了来自地中海研究支持天,诺华。Singer已收到个人赔偿咨询、担任科学顾问委员会说,与Acorda疗法或其他活动,拜耳,生原体,EMD Serono,基因泰克,诺华制药、赛诺菲安万特Genzyme, Teva。Singer收到Acorda研究支持疗法,Alkermes公司生原体,落实的诺华,罗氏公司,赛诺菲安万特Genzyme。福克斯博士已经收到个人赔偿咨询、担任科学顾问委员会说,与Acorda疗法或其他活动,拜耳,生原体,Chugai,礼来,EMD Serono, Genzyme,诺华,小野,Opexa疗法,罗氏公司,赛诺菲,Teva神经科学。福克斯博士收到Acorda研究支持疗法,拜耳,生原体,Chugai,礼来,EMD Serono, Genzyme,诺华,小野,Opexa疗法,罗氏公司,赛诺菲,Teva神经科学。 Dr. Arnold has nothing to disclose. Dr. Ford has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Genzyme, Novartis, Actelion. Dr. Ford has received personal compensation in an editorial capacity for Delaware Medical Group. Dr. Ford has received research support from Actelion, Adamas, Alkermes, Biogen, Genentech, Genzyme, Mallinckrodt, Medday, Novartis, Roche, Sanofi Aventis, Teva, TG Therapeutics. Dr. Weinstock-Guttman has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen Idec, EMD Serono, Genentech, Novartis, Mallinckrodt, and Celgene. Dr. Weinstock-Guttman has received research support from Biogen Idec, Novartis, and Genentech. Dr. Bar-Or has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Atara Biotherapeutics, Biogen, Celgene/Receptos, Genentech/Roche, GlaxoSmithKline, Medimmune, Merck/EMD Serono, Novartis, Sanofi-Genzyme. Dr. Bar-Or has received research support from Atara Biotherapeutics, Biogen, Celgene/Receptos, Genentech/Roche, GlaxoSmithKline, Medimmune, Merck/EMD Serono, Novartis, Sanofi-Genzyme. Dr. Mientus has nothing to disclose. Dr. Sienkiewicz has nothing to disclose. Dr. Zhang has nothing to disclose. Dr. Karan has nothing to disclose. Dr. Tenenbaum has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Novartis. Dr. Tenenbaum holds stock and/or stock options in Novartis which sponsored research in which Dr. Tenenbaum was involved as an investigator.
