穿心莲内酯在非活动进展性多发性硬化症中的疗效：一项前瞻性探索性双盲、平行组、随机、安慰剂对照试验。
Efficacy of andrographolide in not active progressive multiple sclerosis: a prospective exploratory double-blind, parallel-group, randomized, placebo-controlled trial.
机构信息
Neurology Department, Faculty of Medicine, Pontificia Universidad Católica de Chile, Diagonal Paraguay, 362, 5° floor, Santiago, Chile.
Neurology, Hospital Dr. Sótero del Río, Av. Concha y Toro, 3459, Santiago, Chile.
出版信息
BMC Neurol. 2020 May 7;20(1):173. doi: 10.1186/s12883-020-01745-w.
BACKGROUND
Multiple sclerosis (MS) is a chronic immune mediated disease and the progressive phase appears to have significant neurodegenerative mechanisms. The classification of the course of progressive MS (PMS) has been re-organized into categories of active vs. not active inflammatory disease and the presence vs. absence of gradual disease progression. Clinical trial experience to date in PMS with anti-inflammatory medications has shown limited effect. Andrographolide is a new class of anti-inflammatory agent, that has been proposed as a potential drug for autoimmune disorders, including MS. In the present trial, we perform an exploratory pilot study on the efficacy and safety of andrographolide (AP) compared to placebo in not active PMS.
METHODS
A pilot clinical trial using 140 mg oral AP or placebo twice daily for 24 months in patients with not active primary or secondary progressive MS was conducted. The primary efficacy endpoint was the mean percentage brain volume change (mPBVC). Secondary efficacy endpoints included 3-month confirmed disability progression (3-CDP) and mean EDSS change.
RESULTS
Forty-four patients were randomized: 23 were assigned to the AP group, and 21 were assigned to the placebo group. The median baseline EDSS of both groups was 6.0. Annualized mPBVC was - 0.679% for the AP group and - 1.069% for the placebo group (mean difference: -0.39; 95% CI [- 0.836-0.055], p = 0.08, relative reduction: 36.5%). In the AP group, 30% had 3-CDP compared to 41% in the placebo group (HR: 0.596; 95% CI [0.200-1.777], p = 0.06). The mean EDSS change was - 0.025 in the AP group and + 0.352 in the placebo group (mean difference: 0.63, p = 0.042). Adverse events related to AP were mild rash and dysgeusia.
CONCLUSIONS
AP was well tolerated and showed a potential effect in reducing brain atrophy and disability progression, that need to be further evaluated in a larger clinical trial.
TRIAL REGISTRATION
ClinicalTrials.gov NCT02273635 retrospectively registered on October 24th, 2014.
背景
多发性硬化症（MS）是一种慢性免疫介导疾病，进展期似乎存在明显的神经退行性机制。进展型多发性硬化症（PMS）的分类已重新分为活动与非活动炎症性疾病以及逐渐进展与无进展两类。迄今为止，PMS 患者使用抗炎药物进行临床试验的效果有限。穿心莲内酯是一种新型抗炎药物，已被提议作为治疗包括多发性硬化症在内的自身免疫性疾病的潜在药物。在本试验中，我们在非活动型 PMS 患者中进行了一项关于穿心莲内酯（AP）与安慰剂相比的疗效和安全性的探索性试点研究。
方法
一项试点临床试验，采用 140mg 口服 AP 或安慰剂，每日 2 次，共 24 个月，用于非活动性原发性或继发性进展性 MS 患者。主要疗效终点为脑容量变化的平均百分比（mPBVC）。次要疗效终点包括 3 个月确认的残疾进展（3-CDP）和 EDSS 平均变化。
结果
44 例患者被随机分配：23 例分配到 AP 组，21 例分配到安慰剂组。两组的中位基线 EDSS 均为 6.0。AP 组的年平均 mPBVC 为-0.679%，安慰剂组为-1.069%（平均差异：-0.39；95%CI[-0.836-0.055]，p=0.08，相对减少：36.5%）。AP 组有 30%发生 3-CDP，安慰剂组为 41%（HR：0.596；95%CI[0.200-1.777]，p=0.06）。AP 组的 EDSS 平均变化为-0.025，安慰剂组为+0.352（平均差异：0.63，p=0.042）。与 AP 相关的不良反应为轻度皮疹和味觉障碍。
结论
AP 耐受性良好，显示出降低脑萎缩和残疾进展的潜在效果，需要在更大规模的临床试验中进一步评估。
试验注册
ClinicalTrials.gov NCT02273635 于 2014 年 10 月 24 日回顾性注册。
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