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
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
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DOI：
10.1002/art.27327
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发表时间：
2010-04-01
影响因子：
--
通讯作者：
Davis, Matthew W.
中科院分区：
文献类型：
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作者：
Terkeltaub, Robert A.;Furst, Daniel E.;Davis, Matthew W.
目标。尽管秋水仙碱广泛使用，但口服秋水仙碱治疗急性痛风的证据基础仍然有限。本试验的目的是比较低剂量秋水仙碱（缩短为1小时）和高剂量秋水仙碱（延长超过6小时）与安慰剂在痛风发作中的作用，使用在健康志愿者中产生可比较的最大血浆浓度的方案。这项多中心、随机、双盲、安慰剂对照、平行组研究比较了自我服用低剂量秋水仙碱（总1.8 mg超过1小时）和高剂量秋水仙碱（总4.8 mg超过6小时）与安慰剂。主要终点为无急救药物治疗24小时疼痛减轻50%。意向治疗分析中有184例患者。低剂量组74例患者中有28例（37.8%）有应答，高剂量组52例患者中有17例（32.7%）有应答，安慰剂组58例患者中有9例（15.5%）有应答（P = 0.005和P = 0.034，分别与安慰剂组比较）。低剂量组23例（31.1%）患者在24小时内接受了抢救药物治疗（P = 0.027），高剂量组18例（34.6%）患者（P = 0.103），安慰剂组29例（50.0%）患者接受了抢救药物治疗。低剂量组的不良事件（AE）概况与安慰剂组相似，优势比（OR）为1.5（95%可信区间[95% CI] 0.7-3.2）。与低剂量秋水仙碱或安慰剂相比，高剂量秋水仙碱明显与更多的腹泻、呕吐和其他不良事件相关。高剂量秋水仙碱组，40例（76.9%）患者出现腹泻（OR为21.3 [95% CI 7.9-56.9]）， 10例（19.2%）患者出现严重腹泻，9例（17.3%）患者出现呕吐。低剂量秋水仙碱组，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。与高剂量秋水仙碱相比，低剂量秋水仙碱的最大血浆浓度和早期痛风发作疗效相当，安全性与安慰剂没有区别。
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 >= 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.