Hunt Richard H, Harper Sean, Watson Douglas J, Yu Chang, Quan Hui, Lee Michael, Evans Judith K, Oxenius Bettina
Division of Gastroenterology, McMaster University Medical Center, Hamilton, Ontario, Canada.
Am J Gastroenterol. 2003 Aug;98(8):1725-33. doi: 10.1111/j.1572-0241.2003.07598.x.
Etoricoxib is a selective cyclooxygenase inhibitor that in clinical studies has improved the signs and symptoms of osteoarthritis and rheumatoid arthritis and reduced the potential for GI injury. The incidence of endoscopically detected ulcers and of clinically important upper GI events (perforations, ulcers, and bleeding episodes) was compared in patients taking etoricoxib or nonselective nonsteroidal anti-inflammatory drugs (NSAIDs).
Upper GI endoscopy was performed at intervals over 12 wk in 680 patients taking etoricoxib 120 mg once daily, ibuprofen 800 mg three times daily, or placebo in a randomized, parallel-group, double-blind study. Survival analysis was used to analyze time-to-event data for the incidence of gastric or duodenal ulcers (> or =3 mm and > or =5 mm), and the log rank test was used to compare the cumulative incidence between treatment groups. A combined analysis of upper GI events in all 10 Phase II/III clinical trials of etoricoxib (60, 90, or 120 mg) versus nonselective NSAIDs (naproxen, ibuprofen, or diclofenac) for osteoarthritis, rheumatoid arthritis, and chronic low back pain was conducted. Investigators reported potential events for adjudication by an external, blinded committee, using prespecified criteria to confirm events. All events that occurred during active treatment periods (maximum 792 days) or within 14 days of stopping treatment were included in the analysis. Time to first event was evaluated using survival analysis; the Kaplan-Meier method was used to determine the cumulative incidence, and relative risk was estimated with the Cox proportional hazards model.
In the endoscopy study, the cumulative incidence of ulcers >/=3 mm at 12 wk in the ibuprofen group (17%) was significantly higher than in the etoricoxib group (8.1%, p < 0.001); similar results were seen for ulcers >/=5 mm. In the placebo group, the rate of ulcers >/=3 mm was 1.86%. Of 3142 patients treated with once-daily etoricoxib and 1828 patients treated with a nonselective NSAID (ibuprofen, naproxen, or diclofenac), 82 patients with investigator-reported upper GI events (71 confirmed) were eligible for the combined analysis. For etoricoxib versus NSAIDs, the rate per 100 patient-yr for confirmed events was 1.16 versus 3.05 (relative risk = 0.44, 95% CI = 0.27-0.72, p < 0.001), whereas that for investigator-reported events was 1.35 versus 3.42 (relative risk = 0.47, 95% CI = 0.30-0.74, p = 0.001). Results were driven primarily by studies with naproxen as the comparator.
The incidence of endoscopically detected ulcers was significantly lower with etoricoxib 120 mg than with ibuprofen 2400 mg. Treatment with etoricoxib reduced the incidence of investigator-reported and confirmed adverse upper GI events by approximately 50% compared with treatment with nonselective NSAIDs.
依托考昔是一种选择性环氧化酶抑制剂，在临床研究中已改善骨关节炎和类风湿关节炎的体征和症状，并降低胃肠道损伤的可能性。比较服用依托考昔或非选择性非甾体抗炎药（NSAIDs）的患者内镜检查发现溃疡和具有临床意义的上消化道事件（穿孔、溃疡和出血事件）的发生率。
在一项随机、平行组、双盲研究中，对680例每日一次服用120 mg依托考昔、每日三次服用800 mg布洛芬或服用安慰剂的患者，在12周内定期进行上消化道内镜检查。生存分析用于分析胃或十二指肠溃疡（≥3 mm和≥5 mm）发生率的事件发生时间数据，对数秩检验用于比较治疗组之间的累积发生率。对依托考昔（60、90或120 mg）与非选择性NSAIDs（萘普生、布洛芬或双氯芬酸）用于骨关节炎、类风湿关节炎和慢性下腰痛的所有10项II/III期临床试验中的上消化道事件进行了综合分析。研究人员报告潜在事件，由外部盲法委员会根据预先设定的标准进行判定以确认事件。在积极治疗期（最长792天）或停药后14天内发生的所有事件均纳入分析。使用生存分析评估首次事件发生时间；采用Kaplan-Meier方法确定累积发生率，并使用Cox比例风险模型估计相对风险。
在内镜检查研究中，布洛芬组12周时≥3 mm溃疡的累积发生率（17%）显著高于依托考昔组（8.1%，p<0.001）；≥5 mm溃疡的结果相似。在安慰剂组中，≥3 mm溃疡的发生率为1.86%。在3142例每日一次服用依托考昔的患者和1828例服用非选择性NSAIDs（布洛芬、萘普生或双氯芬酸）的患者中，82例有研究人员报告的上消化道事件（71例得到确认）符合综合分析条件。对于依托考昔与NSAIDs，每100患者年确认事件的发生率分别为1.16和3.05（相对风险=0.44，95%CI=0.27-0.72，p<0.001），而研究人员报告事件的发生率分别为1.35和3.42（相对风险=0.47，95%CI=0.30-0.74，p=0.001）。结果主要由以萘普生为对照的研究得出。
120 mg依托考昔内镜检查发现溃疡的发生率显著低于2400 mg布洛芬。与非选择性NSAIDs治疗相比，依托考昔治疗使研究人员报告的和得到确认的上消化道不良事件发生率降低约50%。
