Watson D J, Bolognese J A, Yu C, Krupa D, Curtis S
Merck Research Laboratories, West Point, PA 19486, USA.
Curr Med Res Opin. 2004 Dec;20(12):1899-908. doi: 10.1185/030079904X12681.
Most nonsteroidal anti-inflammatory drugs (NSAIDs) are non-selective cyclooxygenase-1 (COX-1) and COX-2 inhibitors and are associated with upper gastrointestinal (GI) dyspeptic symptoms often resulting in GI co-medication usage or treatment discontinuation.
To compare the rates of new use of gastroprotective agents and discontinuations due to dyspepsia with the COX-2 selective inhibitor etoricoxib compared with non-selective NSAIDs.
This pre-specified combined analysis used data from nine randomized, double-blind, controlled, clinical trials with etoricoxib in patients with osteoarthritis, rheumatoid arthritis, chronic low back pain, or ankylosing spondylitis. The cumulative incidences of (1) new use (new prescription or increased dose) of gastroprotective agents (GPA) and (2) discontinuation due to dyspeptic symptoms were compared among patients treated with etoricoxib (60 mg, 90 mg, or 120 mg daily) vs. non-selective NSAIDs (diclofenac 50 mg. t.i.d. or naproxen 500 mg. b.i.d.).
The overall rates/100 patient-years for new use of GPAs were 9.1 and 13.0 for etoricoxib and NSAIDs, respectively (RR = 0.75; 95% confidence interval [CI] 0.64, 0.89; p < 0.001). A benefit with etoricoxib was seen in the first 6 months when most new GPA usage occurred; after 6 months new use of GPAs was similar between etoricoxib and NSAIDs. The rates/100 patient-years of treatment discontinuation due to dyspeptic symptoms with etoricoxib and NSAIDs were 1.5 and 2.7, respectively (RR = 0.60; 95% CI 0.41, 0.87; p = 0.007). Analyses of placebo-controlled treatment periods showed significantly more new GPA use and more discontinuations due to dyspeptic symptoms with NSAIDs vs. placebo, but not with etoricoxib vs. placebo.
In this combined analysis of clinical trials of patients with OA, RA, chronic low back pain, or AS, new use of gastroprotective agents was significantly lower with etoricoxib than with the comparator non-selective NSAIDs during the initial 6 months of treatment and similar thereafter. There were significantly fewer discontinuations for dyspeptic symptoms with etoricoxib than with NSAIDs over the entire follow-up period.
大多数非甾体抗炎药（NSAIDs）是非选择性环氧化酶-1（COX-1）和COX-2抑制剂，与上消化道（GI）消化不良症状相关，常导致胃肠道联合用药或停药。
比较COX-2选择性抑制剂依托考昔与非选择性NSAIDs在胃保护剂新使用率和因消化不良停药率方面的差异。
这项预先设定的综合分析使用了9项随机、双盲、对照临床试验的数据，这些试验涉及骨关节炎、类风湿关节炎、慢性下腰痛或强直性脊柱炎患者使用依托考昔的情况。比较了接受依托考昔（每日60mg、90mg或120mg）与非选择性NSAIDs（双氯芬酸50mg，每日三次或萘普生500mg，每日两次）治疗的患者中，（1）胃保护剂（GPA）新使用（新处方或剂量增加）和（2）因消化不良症状停药的累积发生率。
依托考昔和NSAIDs的GPA新使用率/100患者年分别为9.1和13.0（相对风险[RR]=0.75；95%置信区间[CI]0.64，0.89；p<0.001）。在大多数新的GPA使用发生的前6个月，依托考昔显示出益处；6个月后，依托考昔和NSAIDs之间的GPA新使用率相似。依托考昔和NSAIDs因消化不良症状导致的治疗停药率/100患者年分别为1.5和2.7（RR=0.60；95%CI0.41，0.87；p=0.007）。安慰剂对照治疗期的分析显示，与安慰剂相比，NSAIDs导致更多的GPA新使用和因消化不良症状导致更多的停药，但依托考昔与安慰剂相比则不然。
在这项针对骨关节炎、类风湿关节炎、慢性下腰痛或强直性脊柱炎患者的临床试验综合分析中，在治疗的最初6个月，依托考昔的胃保护剂新使用率显著低于对照非选择性NSAIDs，此后相似。在整个随访期内，依托考昔因消化不良症状导致的停药明显少于NSAIDs。
