利妥昔单抗治疗伴或不伴IgG4自身抗体的难治性慢性炎性脱髓鞘性多发性神经病的疗效和安全性（RECIPE）：一项双盲、随机、安慰剂对照临床试验方案
Efficacy and Safety of Rituximab in Refractory CIDP With or Without IgG4 Autoantibodies (RECIPE): Protocol for a Double-Blind, Randomized, Placebo-Controlled Clinical Trial.
作者信息
Shimizu Shinobu, Iijima Masahiro, Fukami Yuki, Tamura Natsuko, Nakatochi Masahiro, Ando Masahiko, Nishi Ryoji, Koike Haruki, Kaida Kenichi, Koga Michiaki, Kanda Takashi, Ogata Hidenori, Kira Jun-Ichi, Mori Masahiro, Kuwabara Satoshi, Katsuno Masahisa
机构信息
Department of Advanced Medicine, Nagoya University Hospital, Nagoya, Japan.
Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
出版信息
JMIR Res Protoc. 2020 Apr 1;9(4):e17117. doi: 10.2196/17117.
BACKGROUND
Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an immune-mediated peripheral neuropathy that is currently classified into several clinical subtypes, which are presumed to have different pathogenic mechanisms. Recently, studies identified a subgroup of patients with CIDP who were positive for IgG4 autoantibodies against paranodal proteins, such as neurofascin-155 and contactin-1, who respond poorly to first-line therapies for typical CIDP, including intravenous immunoglobulin therapy.
OBJECTIVE
This study aims to evaluate the efficacy and safety of intravenous rituximab according to IgG4 autoantibody status in patients with refractory CIDP.
METHODS
The Evaluation of the Efficacy and Safety of Rituximab in Refractory CIDP Patients with IgG4 Autoantibodies in the Exploratory Clinical (RECIPE) trial consists of 2 cohorts: a multicenter, placebo-controlled, randomized study cohort of 15 patients with IgG4 autoantibody-positive CIDP (rituximab:placebo = 2:1) and an open-label trial cohort of 10 patients with antibody-negative CIDP. The primary endpoint is improvement in functional outcome assessed using the adjusted Inflammatory Neuropathy Cause and Treatment Disability Scale score at 26, 38, or 52 weeks after the start of treatment with rituximab in patients with CIDP and anti-paranodal protein antibodies. Secondary outcome measures include grip strength, manual muscle testing sum scores, results of nerve conduction studies, and other functional scales.
RESULTS
We plan to enroll 25 cases for the full analysis set. Recruitment is ongoing, with 14 patients enrolled as of January 2020. Enrollment will close in September 2020, and the study is planned to end in December 2021.
CONCLUSIONS
This randomized controlled trial will determine if rituximab is safe and effective in patients with anti-paranodal antibodies. An open-label study will provide additional data on the effects of rituximab in patients with antibody-negative CIDP. The results of the RECIPE trial are expected to provide evidence for the positioning of rituximab as a pathogenesis-based therapeutic for refractory CIDP.
TRIAL REGISTRATION
ClinicalTrials.gov NCT03864185, https://clinicaltrials.gov/ct2/show/NCT03864185 ; The Japan Registry of Clinical Trials jRCT2041180037, https://jrct.niph.go.jp/en-latest-detail/jRCT2041180037.
INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/17117.
背景
慢性炎性脱髓鞘性多发性神经根神经病（CIDP）是一种免疫介导的周围神经病，目前分为几种临床亚型，推测其致病机制不同。最近，研究发现CIDP患者中有一组针对结旁蛋白（如神经束蛋白-155和接触蛋白-1）的IgG4自身抗体呈阳性，这些患者对包括静脉注射免疫球蛋白治疗在内的典型CIDP一线治疗反应不佳。
目的
本研究旨在根据IgG4自身抗体状态评估静脉注射利妥昔单抗治疗难治性CIDP患者的疗效和安全性。
方法
利妥昔单抗治疗难治性IgG4自身抗体阳性CIDP患者疗效和安全性的探索性临床评估（RECIPE）试验包括2个队列：一个多中心、安慰剂对照、随机研究队列，共15例IgG4自身抗体阳性CIDP患者（利妥昔单抗：安慰剂=2:1）；一个开放标签试验队列，共10例抗体阴性CIDP患者。主要终点是在CIDP和抗结旁蛋白抗体患者开始使用利妥昔单抗治疗后26、38或52周，使用调整后的炎性神经病病因和治疗残疾量表评分评估功能结局的改善情况。次要结局指标包括握力、徒手肌力测试总分、神经传导研究结果和其他功能量表。
结果
我们计划纳入25例患者进行全分析集分析。招募工作正在进行中，截至2020年1月已招募14例患者。招募将于2020年9月结束，研究计划于2021年12月结束。
结论
这项随机对照试验将确定利妥昔单抗对抗结旁抗体患者是否安全有效。一项开放标签研究将提供关于利妥昔单抗对抗体阴性CIDP患者疗效的更多数据。RECIPE试验的结果有望为利妥昔单抗作为难治性CIDP基于发病机制的治疗方法的定位提供证据。
试验注册
ClinicalTrials.gov NCT03864185，https://clinicaltrials.gov/ct2/show/NCT03864185 ；日本临床试验注册中心jRCT2041180037，https://jrct.niph.go.jp/en-latest-detail/jRCT2041180037。
国际注册报告识别码（IRRID）：DERR1-10.2196/17117。
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