针对性释放布德索尼德与安慰剂在IgA脏病患者 (NEFIGAN):一个双盲,随机,安慰剂控制的2b期试验
Bengt C Fellström1, Jonathan Barratt2, Heather Cook3
1Uppsala University Hospital, Uppsala, Sweden.
Lancet (London, England)
|April 2, 2017
概括
在IgA脏病患者中,有针对性的释放布德索尼德显著降低了蛋白尿,这表明末期脏病的风险较低. 这提供了针对粘膜免疫的潜在新疗法.
科学领域:
- 肝脏病学
- 免疫学
- 胃肠病学
背景情况:
- 在20% - 40%的患者中,IgA脏病 (IgAN) 涉及粘膜免疫功能障碍和脏IgA沉积,导致功能障碍和末期脏病.
- 目前对IgAN的治疗方法有限,这凸显了针对疾病潜在机制的新型治疗策略的需要.
研究的目的:
- 在患有IgA脏病的患者中评估一种新型的定向释放布德索尼德 (TRF-布德索尼德) 的安全性和有效性.
- 评估药物减少蛋白尿和可能减缓疾病进展的能力.
主要方法:
- 一个随机的,双盲的,安慰剂控制的2b期试验 (NEFIGAN) 涉及150名患者,尽管经过优化氨酸 - 血管素系统 (RAS) 阻塞,但经过活检确认的Igan和持续的蛋白尿.
- 患者接受了每天16毫克的TRF- 布德索尼德,每天8毫克的TRF- 布德索尼德或安慰剂9个月,其中蛋白尿 (尿中蛋白质肌素比率- UPCR) 是主要的终点.
- 在整个试验中进行了安全评估,包括对不良事件的监测.
主要成果:
- 与安慰剂 (p=0. 0066) 相比,在9个月内,TRF- 布德索尼德治疗 (每天16毫克和每天8毫克组合) 导致UPCR的平均值显著下降24. 4%.
- 与安慰剂相比,16 mg/ 天 (27. 3%) 和8 mg/ 天 (21. 5%) 的剂量都显著降低了UPCR.
- 各组的不良事件发生率相似,其中有两个可能与TRF- budesonide相关的严重不良事件.
结论:
- 当添加到优化的RAS阻塞时,TRF- 布德索尼德可以有效地减少IgA脏病患者的蛋白尿症.
- 这种蛋白尿的降低表明病进展到末期的风险可能有所降低.
- TRF- budesonide可能是针对Igan的第一个特异性治疗方法,针对脏表现的肠道粘膜免疫.
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