文摘
摘要目的:对比安慰剂反应的路径研究与其他研究在慢性炎性脱髓鞘多神经病(CIDP)和静脉注射免疫球蛋白(丙种球蛋白)治疗。
背景:“安慰剂反应”是指一个意想不到的改善与安慰剂组和临床试验设计中是一个重要的变量。但是,CIDP试验中,它可以指没有预期的临床恶化与安慰剂。这里,安慰剂反应率的路径研究皮下免疫球蛋白(SCIG)作为CIDP的维持治疗与研究CIDP和其他神经疾病的药物。
设计/方法:在路径研究,丙种球蛋白退出IVIG-dependent受试者在一个免疫球蛋白(免疫球蛋白)的依赖。任何临床恶化restabilized丙种球蛋白(1克/公斤;IgPro10, Privigen®)在10 - 13周;受试者被随机分配到每周SCIG(0.2或0.4克/公斤;IgPro20, Hizentra®)或安慰剂为24周。主要终点是CIDP复发(≥1点增加总调整炎症病变病因和治疗[INCAT]分数)或退出。安慰剂反应在其他的研究中被确定通过PubMed搜索的随机对照试验。
结果:在免疫球蛋白依赖期,28/245(11.4%)的主题没有恶化(10停止其他原因)。的207名受试者进入丙种球蛋白restabilization时期,172年展示CIDP稳定随机安慰剂,SCIG 0.2或0.4克/公斤(n = 57; 57; 58)。在安慰剂组,37%没有复发/撤回,SCIG相比,61%和67%。安慰剂对照试验CIDP的文献报道安慰剂反应或者non-relapse 10 - 55%,使用一系列的结果(例如,医学研究委员会和分数,INCAT)和治疗(例如,丙种球蛋白、甲氨蝶呤)。
结论:路径的研究为临床实践和CIDP试验有重要意义,强调安慰剂效应和CIDP的remitting-relapsing本质功效混杂因素。比较与其他研究问题的原因和研究设计是否能减轻这些影响。
披露:刘易斯博士已经收到个人赔偿咨询、担任科学顾问委员会说,与中超贝林或其他活动,Axelacare, Pharnext,生物监测,Kedrion, NuFactor Optioncare, Grifols。刘易斯博士研究支持Neuraltus和Cytokinetics接收。成Bril博士已经收到个人赔偿咨询、担任科学顾问委员会说,与中超贝林或其他活动,联合,Alnylam、Alexion, Grifols, Octapharma,夏尔,辉瑞和Bionevia。成Bril博士已经收到了来自中超贝林研究支持,联合,Alnylam、Alexion, Grifols, Octapharma,夏尔,Bionevia。范博士Geloven已经收到了来自中超贝林研究支持。哈博士已经收到个人赔偿咨询、担任科学顾问委员会说,与拜耳医疗或其他活动,生原体,Geneuro, Genzyme,落实的默克公司Receptos Celgene公司,诺华,罗氏,CSL贝林。Sobue博士已经收到个人赔偿咨询、担任科学顾问委员会说,与三菱田边制药有限公司或其他活动;武田制药有限公司。Mielke博士已经收到个人赔偿咨询、担任科学顾问委员会说,与中超贝林GmbH或其他活动。朗沃收到个人赔偿咨询博士担任科学顾问委员会说,与中超贝林GmbH或其他活动。 Dr. Durn has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with CSL Behring. Dr. Cornblath has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Acetylon Pharmaceuticals Inc., Alnylam Pharmaceuticals, Annexon Biosciences, Akros Pharma, argenx BVBA, Biotest Pharmaceuticals, Inc., Boehringer Ingelheim, Cigna Health Management, Inc., CSL Behring, DP Clinical, Inc., Grifols S.A., Hansa Medical Inc., Karos Pharmaceuticals, Inc., Merrimack Pharmaceuticals, Inc., Neurocrine Biosciences, Novartis Corp., Octapharma AG, Pharnext SAS, Seattle Genetics, Inc., Sun Pharmaceuticals, Syntimmune. Data Safety Monitoring Board: Pfizer Inc., Ionis Pharmaceuticals, Axovant Sciences LTD., Ampio Pharmaceuticals, PledPharma, Momenta Pharma, Sanofi, GBS CIDP Foundation International. Dr. Cornblath has received personal compensation in an editorial capacity for JPNS. Dr. Cornblath has received compensation The Peripheral Nerve Society. Dr. Cornblath has received royalty, license fees, or contractual rights payments from Acetylon Pharmaceuticals Inc., Akros Pharma, AstraZeneca Pharmaceuticals, LP, Calithera Biosciences, Genentech Inc, Karos Pharma, Neurocrine Biosciences, Merrimack Pharmaceuticals, Inc. Seattle Genetics, Inc., Shire Development, LLC. Dr. Merkies has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Talecris. Dr. Merkies has received personal compensation in an editorial capacity for Journal of the Peripheral Nerve Society. Dr. Van Schaik has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with CSL Behring, Baxter. Dr. Van Schaik has received personal compensation in an editorial capacity for Cochrane Neuromuscular Disease Group. Dr. Van Schaik has received research support from The Netherlands Organization for Scientific Research, Dutch Prinses Beatrix Fonds.
