Impact of patient characteristics on the clinical efficacy of mongersen (GED-0301), an oral Smad7 antisense oligonucleotide, in active Crohn's disease.
Impact of patient characteristics on the clinical efficacy of mongersen (GED-0301), an oral Smad7 antisense oligonucleotide, in active Crohn's disease.
复制标题
患者特征对蒙格森（GED-0301）的临床疗效的影响（GED-0301），一种口服SMAD7反义寡核苷酸，在活性克罗恩病中。
DOI：
10.1111/apt.13526
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发表时间：
2016-03
影响因子：
7.6
通讯作者：
Neurath MF
中科院分区：
文献类型：
--
作者：
Monteleone G;Di Sabatino A;Ardizzone S;Pallone F;Usiskin K;Zhan X;Rossiter G;Neurath MF
在一项2期研究中，一种靶向Smad 7的口服反义寡核苷酸mongersen可有效诱导约60%的活动性克罗恩病（CD）患者的临床缓解。在事后分析中，评价可能影响孟格森治疗疗效和安全性的患者疾病特征。类固醇依赖/耐药、活动性CD患者随机接受Mongersen 10、40或160 mg/天或安慰剂治疗2周;患者随访10周。在第2、4和12周评估这些亚组的临床缓解[克罗恩病活动指数（CDAI）评分<150]和临床应答（CDAI评分降低≥100分）：病程<5/≥5年，人血清C反应蛋白（hsCRP）<3/≥3 mg/L，基线CDAI ≤260/>260。探索了其他患者基线和疾病特征。与安慰剂组相比，接受蒙格生40和160 mg/天治疗但不接受10 mg/天治疗的患者的临床缓解率和应答率显著更高，且与疾病持续时间和hsCRP无关。基线CDAI ≤260的患者在40和160 mg/天剂量下的缓解率显著更高。在基线CDAI >260的患者中，与安慰剂相比，160 mg/天的缓解率在统计学上更高，40 mg/天的缓解率在数值上更好。各治疗组的不良事件发生率相似。Mongersen是安全的，耐受性良好。具有较高CDAI评分的患者在最高孟格森剂量下最常达到临床缓解。在本研究中，疾病持续时间和基线人血清C反应蛋白似乎未显著影响蒙格森的疗效（EudraCT编号：2011 - 002640 - 27）。
In a phase 2 study, mongersen, an oral antisense oligonucleotide targeting Smad7, was effective in inducing clinical remission in approximately 60% of patients with active Crohn's disease (CD). In a post hoc analysis to evaluate those patient disease characteristics that may have influenced the efficacy and safety of mongersen therapy. Patients with steroid‐dependent/resistant, active CD were randomised to mongersen 10, 40 or 160 mg/day or placebo for 2 weeks; patients were followed for 10 weeks. Clinical remission [Crohn's Disease Activity Index (CDAI) score <150] and clinical response (CDAI score reduction ≥100 points) were assessed at weeks 2, 4 and 12 for these subgroups: disease duration <5/≥5 years, human serum C‐reactive protein (hsCRP) <3/≥3 mg/L, and CDAI at baseline ≤260/>260. Additional patient baseline and disease characteristics were explored. Clinical remission and response rates were significantly higher in patients receiving mongersen 40 and 160 mg/day but not 10 mg/day vs. placebo and independent of disease duration and hsCRP. Patients with baseline CDAI ≤260 had significantly higher remission rates with 40 and 160 mg/day. In patients with baseline CDAI >260, remission rates were statistically greater with 160 mg/day and numerically better with 40 mg/day vs. placebo. Adverse event rates were similar across treatment groups. Mongersen was safe and well tolerated. Patients with higher CDAI scores achieved clinical remission most frequently with the highest mongersen dose. Disease duration and baseline human serum C‐reactive protein did not appear to significantly impact efficacy of mongersen in this study (EudraCT Number: 2011‐002640‐27.)