Five-Year Analysis of the Prevention of Colorectal Sporadic Adenomatous Polyps Trial
Five-Year Analysis of the Prevention of Colorectal Sporadic Adenomatous Polyps Trial
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DOI：
10.1038/ajg.2011.116
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发表时间：
2011-06-01
影响因子：
9.8
通讯作者：
Levin, Bernard
中科院分区：
文献类型：
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作者：
Arber, Nadir;Spicak, Julius;Levin, Bernard
方法：对预防结直肠散发性腺瘤性息肉（PreSAP）试验（PRESAP/NCT 00141193/www.clinicaltrials.gov）中的受试者进行研究，以确定5年评估的有效性和安全性。方法：在这项随机、安慰剂对照、双盲试验中，1,561例在研究开始后3个月内切除确诊结直肠腺瘤的受试者在服用塞来昔布3年后进行评估，随后停药2年。在107个初级和二级医疗机构中进行研究，受试者按心脏保护性阿司匹林的使用分层，并随机接受400 mg塞来昔布（933例受试者）或安慰剂（628例受试者）每日一次口服。在第1年，第3年和第5年的疗效通过结肠镜检查进行测量，安全性由研究人员在治疗期间进行测量，并由受试者自我报告收集超过2 years posttreatment.RESULTS：在第5年，主要结局指标是从基线累积测量的新发腺瘤的发生率。塞来昔布组的这一发生率（51.4%）在统计学上显著低于安慰剂组（57.5%; P < 0.001）。同样，塞来昔布组新发晚期腺瘤的累积发生率（10.0%）显著低于安慰剂组（13.8%; P = 0.007）。然而，第5年间隔测量，这不是累积的，也没有考虑到前几年的发生率，显示在停止治疗2年后，塞来昔布组（27.0%）发生新腺瘤的可能性是安慰剂组（16.3%; P < 0.0001）的1.66倍。同样，塞来昔布组新发晚期腺瘤的患者百分比（5.0%）显著高于安慰剂组（3.8%）（P = 0.0072）。从基线到第5年的安全性评价表明，严重心脏疾病的风险（相对风险（RR）1.66; 95%置信区间（CI）1.01-2.73），选定的肾脏/高血压事件（RR 1.35; 95% CI 1.09-1.68）和一般血管（RR 1.34; 95% CI 1.08-1.68）和心脏疾病（RR 1.59; 95%CI 1.12-2.26），服用塞来昔布的患者高于服用安慰剂的患者。塞来昔布组新发和晚期腺瘤发生率的5年累积测量值显著低于安慰剂组，但是安慰剂组的这些测量的5年间隔率显著低于塞来昔布组，这可能提示环加氧酶-2抑制的释放。与先前报告的一致，塞来昔布治疗相关的肾脏/高血压事件和心脏疾病风险增加，要求谨慎选择患者。
OBJECTIVES: Subjects in the Prevention of Colorectal Sporadic Adenomatous Polyps (PreSAP) trial (PRESAP/NCT00141193/www.clinicaltrials.gov) were studied to determine efficacy and safety at a year 5 assessment.METHODS: In this randomized, placebo-controlled, double-blind trial, 1,561 subjects with diagnosed colorectal adenomas removed within 3 months of the study's initiation were assessed after similar to 3 years on celecoxib followed by 2 years off. Studied in 107 primary and secondary care settings, subjects were stratified by cardioprotective aspirin use and randomized to receive orally 400 mg celecoxib (933 subjects) or placebo (628 subjects) once daily. Efficacy was measured by colonoscopy at years 1, 3, and 5, and safety was measured by investigators for the on-treatment period and collected by subject self-report over 2 years post-treatment.RESULTS: At year 5, the primary outcome measure was the rate of new adenomas measured cumulatively from baseline. This rate was statistically significantly lower in the celecoxib group (51.4%) than in the placebo group (57.5%; P < 0.001). Similarly, the cumulative rate of new advanced adenomas was significantly lower in the celecoxib group (10.0%) than in the placebo group (13.8%; P = 0.007). However, the year 5 interval measure, which was not cumulative and did not take the rates of previous years into account, showed that after 2 years off treatment, the celecoxib group (27.0%) was 1.66 times more likely to have new adenomas than the placebo group (16.3%; P < 0.0001). Similarly, the percentage of patients with new advanced adenomas was significantly higher in the celecoxib group (5.0%) than in the placebo group (3.8%) (P = 0.0072). The evaluation of safety from baseline through year 5 indicated that the risks of serious cardiac disorders (relative risk (RR) 1.66; 95% confidence interval (CI) 1.01-2.73), selected renal/hypertension events (RR 1.35; 95% CI 1.09-1.68), and general vascular (RR 1.34; 95% CI 1.08-1.68) and cardiac disorders (RR 1.59; 95% CI 1.12-2.26) were higher in those taking celecoxib than in those on placebo.CONCLUSIONS: The year 5 cumulative measures of the incidence of new and advanced adenomas were significantly lower in the celecoxib group than in the placebo group, but the year 5 interval rates of these measures were significantly lower in the placebo group than the celecoxib group, perhaps suggesting a release of cyclooxygenase-2 inhibition. Consistent with what has been previously reported, increased risk of renal/hypertension events and cardiac disorders associated with celecoxib therapy mandates caution in patient selection.