Watson D J, Harper S E, Zhao P L, Quan H, Bolognese J A, Simon T J
Merck Research Labs, West Point, PA, USA.
Arch Intern Med. 2000 Oct 23;160(19):2998-3003. doi: 10.1001/archinte.160.19.2998.
Most nonsteroidal anti-inflammatory drugs (NSAIDs) are nonselective cyclooxygenase (COX-1 and COX-2) inhibitors and are associated with a variety of upper gastrointestinal (GI) tract symptoms. The roles of COX-1 and COX-2 in the pathogenesis of these symptoms are unclear. To test whether COX-2 inhibition with rofecoxib would have greater GI tolerability than nonselective COX-1 and COX-2 inhibition, we compared the incidences of (1) treatment discontinuations for GI adverse events (AEs) and (2) prespecified dyspeptic-type GI AEs among patients with osteoarthritis treated with rofecoxib vs NSAIDs.
A prespecified, combined analysis of investigator-reported GI AEs in all 8 double-blind, randomized, phase 2b/3 osteoarthritis trials of rofecoxib was conducted. Patients included men and women with osteoarthritis (N = 5435); there was no upper age limit for entry. Treatments tested included rofecoxib, 12.5, 25, or 50 mg (combined), vs ibuprofen, diclofenac, or nabumetone (combined). Primary outcomes were the time (by survival analysis) to (1) treatment discontinuation due to GI AEs and (2) first reported dyspeptic-type GI AE. Between-treatment comparisons were made by log-rank test.
The number of treatment discontinuations caused by GI AEs during 12 months was significantly lower (P=.02) with rofecoxib vs NSAIDs (8.2 vs 12.0 per 100 patient-years; relative risk, 0.70; 95% confidence interval, 0.52-0.94). The incidence of prespecified dyspeptic-type GI AEs during the first 6 months was significantly lower (P=.02) with rofecoxib vs NSAIDs (69.3 vs 85.2 per 100 patient-years; relative risk, 0.85; 95% confidence interval, 0.74-0.97). However, the difference between treatments in dyspeptic-type GI AEs was attenuated after 6 months.
Rofecoxib was associated with a lower incidence of treatment discontinuations due to GI AEs over 12 months and a lower incidence of dyspeptic-type GI AEs over 6 months than treatment with nonselective COX inhibitors, or NSAIDs. Arch Intern Med. 2000;160:2998-3003
大多数非甾体抗炎药（NSAIDs）是非选择性环氧化酶（COX - 1和COX - 2）抑制剂，与多种上消化道（GI）道症状相关。COX - 1和COX - 2在这些症状发病机制中的作用尚不清楚。为了测试罗非昔布抑制COX - 2是否比非选择性抑制COX - 1和COX - 2具有更高的胃肠道耐受性，我们比较了用罗非昔布与NSAIDs治疗的骨关节炎患者中，（1）因胃肠道不良事件（AE）而停药的发生率，以及（2）预先指定的消化不良型胃肠道AE的发生率。
对罗非昔布的所有8项双盲、随机、2b/3期骨关节炎试验中研究者报告的胃肠道AE进行预先指定的综合分析。患者包括患有骨关节炎的男性和女性（N = 5435）；入组无年龄上限。测试的治疗方法包括罗非昔布12.5、25或50mg（合并），与布洛芬、双氯芬酸或萘丁美酮（合并）。主要结局是（通过生存分析）达到以下情况的时间：（1）因胃肠道AE停药，以及（2）首次报告的消化不良型胃肠道AE。组间比较采用对数秩检验。
12个月期间，罗非昔布组因胃肠道AE导致的停药人数显著低于NSAIDs组（P = 0.02）（每100患者年分别为8.2例和12.0例；相对风险，0.70；95%置信区间，0.52 - 0.94）。前6个月预先指定的消化不良型胃肠道AE的发生率，罗非昔布组显著低于NSAIDs组（P = 0.02）（每100患者年分别为69.3例和85.2例；相对风险，0.85；95%置信区间，0.74 - 0.97）。然而，6个月后，治疗组间在消化不良型胃肠道AE方面的差异有所减弱。
与非选择性COX抑制剂或NSAIDs治疗相比，罗非昔布在12个月内因胃肠道AE导致的停药发生率较低，在6个月内消化不良型胃肠道AE的发生率也较低。《内科学文献》。2000年；160:2998 - 3003
