Merkies Ingemar S J, van Schaik Ivo N, Bril Vera, Hartung Hans-Peter, Lewis Richard A, Sobue Gen, Lawo John-Philip, Mielke Orell, Cornblath David R
Department of Neurology, Maastricht University Medical Center, Maastricht, the Netherlands.
Department of Neurology, Curaçao Medical Center, Willemstad, Curaçao.
J Peripher Nerv Syst. 2022 Jun;27(2):159-165. doi: 10.1111/jns.12487. Epub 2022 Mar 15.
Clinical trials in chronic inflammatory demyelinating polyneuropathy (CIDP) often assess efficacy using the ordinal Inflammatory Neuropathy Cause and Treatment (INCAT) disability score. Here, data from the PATH study was reanalyzed using change in Inflammatory Rasch-built Overall Disability Scale (I-RODS) to define CIDP relapse instead of INCAT. The PATH study comprised an intravenous immunoglobulin (IVIG) dependency period and an IVIG (IgPro10 [Privigen]) restabilization period; subjects were then randomized to weekly maintenance subcutaneous immunoglobulin (SCIG; IgPro20 [Hizentra]) 0.2 g/kg or 0.4 g/kg or placebo for 24 weeks. CIDP relapse was defined as ≥1-point deterioration in adjusted INCAT, with a primary endpoint of relapse or withdrawal rates. This retrospective exploratory analysis redefined relapse using I-RODS via three different cut-off methods: an individual variability method, fixed cut-off of ≥8-point deterioration on I-RODS centile score or ≥4-point deterioration on I-RODS raw score. Relapse or withdrawal rates were 47% for placebo, 34% for 0.2 g/kg IgPro20 and 19% for 0.4 g/kg IgPro20 using the raw score; 40%, 28% and 15%, respectively using the centile score, and 49%, 40% and 27%, respectively using the individual variability method. IgPro20 was shown to be efficacious as a maintenance therapy for CIDP when relapse was defined using I-RODS. A stable response pattern was shown for I-RODS across various applied cut-offs, which could be applied in future clinical trials.
慢性炎症性脱髓鞘性多发性神经病(CIDP)的临床试验通常使用序贯性炎症性神经病病因与治疗(INCAT)残疾评分来评估疗效。在此,对PATH研究的数据进行了重新分析,采用炎症性拉施构建的总体残疾量表(I-RODS)的变化来定义CIDP复发,而非使用INCAT。PATH研究包括静脉注射免疫球蛋白(IVIG)依赖期和IVIG(IgPro10 [Privigen])再稳定期;然后将受试者随机分为接受每周一次皮下注射免疫球蛋白(SCIG;IgPro20 [Hizentra])0.2 g/kg或0.4 g/kg或安慰剂治疗24周。CIDP复发定义为校正后的INCAT评分恶化≥1分,主要终点为复发率或撤药率。这项回顾性探索性分析通过三种不同的截断方法,使用I-RODS重新定义复发:个体变异性方法、I-RODS百分位数评分恶化≥8分或I-RODS原始评分恶化≥4分的固定截断值。使用原始评分时,安慰剂组的复发或撤药率为47%,0.2 g/kg IgPro20组为34%,0.4 g/kg IgPro20组为19%;使用百分位数评分时,分别为40%、28%和15%;使用个体变异性方法时,分别为49%、40%和27%。当使用I-RODS定义复发时,IgPro20被证明作为CIDP的维持治疗有效。I-RODS在各种应用的截断值下均显示出稳定的反应模式,可应用于未来的临床试验。