高剂量与低剂量口服秋水仙碱治疗早期急性痛风发作：首个多中心、随机、双盲、安慰剂对照、平行组、剂量比较秋水仙碱研究的24小时结果

High versus low dosing of oral colchicine for early acute gout flare: Twenty-four-hour outcome of the first multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose-comparison colchicine study.

作者信息

Terkeltaub Robert A, Furst Daniel E, Bennett Katherine, Kook Karin A, Crockett R S, Davis Matthew W

机构信息

VAMC San Diego, and University of California, San Diego, CA 92161, USA.

出版信息

Arthritis Rheum. 2010 Apr;62(4):1060-8. doi: 10.1002/art.27327.

DOI:10.1002/art.27327

PMID:20131255

Abstract

OBJECTIVE

Despite widespread use of colchicine, the evidence basis for oral colchicine therapy and dosing in acute gout remains limited. The aim of this trial was to compare low-dose colchicine (abbreviated at 1 hour) and high-dose colchicine (prolonged over 6 hours) with placebo in gout flare, using regimens producing comparable maximum plasma concentrations in healthy volunteers.

METHODS

This multicenter, randomized, double-blind, placebo-controlled, parallel-group study compared self-administered low-dose colchicine (1.8 mg total over 1 hour) and high-dose colchicine (4.8 mg total over 6 hours) with placebo. The primary end point was > or = 50% pain reduction at 24 hours without rescue medication.

RESULTS

There were 184 patients in the intent-to-treat analysis. Responders included 28 of 74 patients (37.8%) in the low-dose group, 17 of 52 patients (32.7%) in the high-dose group, and 9 of 58 patients (15.5%) in the placebo group (P = 0.005 and P = 0.034, respectively, versus placebo). Rescue medication was taken within the first 24 hours by 23 patients (31.1%) in the low-dose group (P = 0.027 versus placebo), 18 patients (34.6%) in the high-dose group (P = 0.103 versus placebo), and 29 patients (50.0%) in the placebo group. The low-dose group had an adverse event (AE) profile similar to that of the placebo group, with an odds ratio (OR) of 1.5 (95% confidence interval [95% CI] 0.7-3.2). High-dose colchicine was associated with significantly more diarrhea, vomiting, and other AEs compared with low-dose colchicine or placebo. With high-dose colchicine, 40 patients (76.9%) had diarrhea (OR 21.3 [95% CI 7.9-56.9]), 10 (19.2%) had severe diarrhea, and 9 (17.3%) had vomiting. With low-dose colchicine, 23.0% of the patients had diarrhea (OR 1.9 [95% CI 0.8-4.8]), none had severe diarrhea, and none had vomiting.

CONCLUSION

Low-dose colchicine yielded both maximum plasma concentration and early gout flare efficacy comparable with that of high-dose colchicine, with a safety profile indistinguishable from that of placebo.

摘要

目的

尽管秋水仙碱被广泛使用，但口服秋水仙碱治疗急性痛风的证据基础仍然有限。本试验的目的是在痛风发作时，将低剂量秋水仙碱（1小时内给药）和高剂量秋水仙碱（6小时内给药）与安慰剂进行比较，采用在健康志愿者中产生可比最大血浆浓度的给药方案。

方法

这项多中心、随机、双盲、安慰剂对照、平行组研究将自行给药的低剂量秋水仙碱（1小时内共1.8毫克）和高剂量秋水仙碱（6小时内共4.8毫克）与安慰剂进行比较。主要终点是在24小时内疼痛减轻≥50%且无需急救药物。

结果

意向性分析中有184例患者。低剂量组74例患者中有28例（37.8%）有反应，高剂量组52例患者中有17例（32.7%）有反应，安慰剂组58例患者中有9例（15.5%）有反应（与安慰剂相比，P值分别为0.005和0.034）。低剂量组23例患者（31.1%）在最初24小时内服用了急救药物（与安慰剂相比，P = 0.027），高剂量组18例患者（34.6%）服用了急救药物（与安慰剂相比，P = 0.103），安慰剂组29例患者（50.0%）服用了急救药物。低剂量组的不良事件（AE）情况与安慰剂组相似，优势比（OR）为1.5（95%置信区间[95%CI]0.7 - 3.2）。与低剂量秋水仙碱或安慰剂相比，高剂量秋水仙碱与更多的腹泻、呕吐及其他不良事件相关。高剂量秋水仙碱组中，40例患者（76.9%）出现腹泻（OR 21.3[95%CI 7.9 - 56.9]），10例（19.2%）出现严重腹泻，9例（17.3%）出现呕吐。低剂量秋水仙碱组中，23.0%的患者出现腹泻（OR 1.9[95%CI 0.8 - 4.8]），无严重腹泻，无呕吐。