罗非昔布、萘普生或安慰剂治疗类风湿关节炎患者12周后胃十二指肠溃疡的发生率：一项多中心、随机、双盲研究。
Incidence of gastroduodenal ulcers in patients with rheumatoid arthritis after 12 weeks of rofecoxib, naproxen, or placebo: a multicentre, randomised, double blind study.
作者信息
Hawkey C J, Laine L, Simon T, Quan H, Shingo S, Evans J
机构信息
University Hospital, Nottingham, United Kingdom.
出版信息
Gut. 2003 Jun;52(6):820-6. doi: 10.1136/gut.52.6.820.
BACKGROUND
Previous studies in patients with osteoarthritis have suggested that the selective cyclooxygenase (COX)-2 inhibitor rofecoxib results in less gastrointestinal damage than non-selective non-steroidal antiinflammatory drugs (NSAIDs). This study compared the incidence of endoscopically detected gastroduodenal ulcers in rheumatoid arthritis patients treated with rofecoxib or a non-selective NSAID.
METHODS
In this multicentre, randomised, double blind, 12 week study, patients with rheumatoid arthritis were allocated to rofecoxib 50 mg once daily (n=219), naproxen 500 mg twice daily (n=220), or placebo (n=221). Endoscopy was performed at baseline and at six and 12 weeks. Lifetable analysis and log rank tests were used to analyse the incidence of gastroduodenal ulcers > or =3 mm. Gastric or duodenal ulcers > or =5 mm and erosions were also evaluated as secondary end points. Tolerability was assessed by adverse events.
RESULTS
The cumulative incidence of ulcers > or =3 mm at 12 weeks was significantly higher in patients on naproxen (25.5%) than in patients receiving rofecoxib (6.8%; difference 18.7% (95% confidence interval (CI) 11.7%, 25.7%); p<0.001) or placebo (2.9%; difference 22.6% (95% CI 16.1%, 29.1%); p<0.001). The difference between rofecoxib (6.8%) and placebo (2.9%) did not reach statistical significance (p=0.066). Results were similar for ulcers > or =5 mm and for mean changes from baseline in the number of gastroduodenal erosions. The overall incidence of clinical adverse events was similar among treatment groups (61% of patients on placebo, 62% in patients on rofecoxib, and 66% in patients on naproxen).
CONCLUSIONS
Rofecoxib 50 mg daily (twice the dose recommended for this patient population) resulted in a lower incidence of endoscopically detected gastroduodenal ulcers and erosions than treatment with naproxen 500 mg twice daily.
背景
先前针对骨关节炎患者的研究表明，选择性环氧化酶（COX）-2抑制剂罗非昔布导致的胃肠道损伤比非选择性非甾体抗炎药（NSAIDs）更少。本研究比较了接受罗非昔布或非选择性NSAIDs治疗的类风湿关节炎患者内镜检查发现的胃十二指肠溃疡发生率。
方法
在这项多中心、随机、双盲、为期12周的研究中，类风湿关节炎患者被分配至每日一次服用50mg罗非昔布组（n = 219）、每日两次服用500mg萘普生组（n = 220）或安慰剂组（n = 221）。在基线、6周和12周时进行内镜检查。采用寿命表分析和对数秩检验分析直径≥3mm的胃十二指肠溃疡发生率。直径≥5mm的胃或十二指肠溃疡以及糜烂也作为次要终点进行评估。通过不良事件评估耐受性。
结果
萘普生组患者在12周时直径≥3mm溃疡的累积发生率（25.5%）显著高于接受罗非昔布治疗的患者（6.8%；差异18.7%（95%置信区间（CI）11.7%，25.7%）；p<0.001）或安慰剂组（2.9%；差异22.6%（95%CI 16.1%，29.1%）；p<0.001）。罗非昔布组（6.8%）与安慰剂组（2.9%）之间的差异未达到统计学显著性（p = 0.066）。直径≥5mm的溃疡以及胃十二指肠糜烂数量相对于基线的平均变化结果相似。各治疗组临床不良事件的总体发生率相似（安慰剂组患者为61%，罗非昔布组患者为62%，萘普生组患者为66%）。
结论
每日服用50mg罗非昔布（该患者群体推荐剂量的两倍）导致内镜检查发现的胃十二指肠溃疡和糜烂发生率低于每日两次服用500mg萘普生的治疗。
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