Lisse Jeffrey R, Perlman Monica, Johansson Gunnar, Shoemaker James R, Schechtman Joy, Skalky Carol S, Dixon Mary E, Polis Adam B, Mollen Arthur J, Geba Gregory P
University of Arizona, Tuscon, USA.
Ann Intern Med. 2003 Oct 7;139(7):539-46. doi: 10.7326/0003-4819-139-7-200310070-00005.
Gastrointestinal (GI) toxicity mediated by dual cyclooxygenase (COX)-1 and COX-2 inhibition of nonsteroidal anti-inflammatory drugs (NSAIDs) can cause serious alterations of mucosal integrity or, more commonly, intolerable GI symptoms that may necessitate discontinuation of therapy. Unlike NSAIDs, rofecoxib targets only the COX-2 isoform.
To assess the tolerability of rofecoxib compared with naproxen for treatment of osteoarthritis.
Randomized, controlled trial.
600 office and clinical research sites.
5557 patients (mean age, 63 years) with a baseline diagnosis of osteoarthritis of the knee, hip, hand, or spine.
Rofecoxib, 25 mg/d, or naproxen, 500 mg twice daily. Use of routine medications, including aspirin, was permitted.
Discontinuation due to GI adverse events (primary end point) and use of concomitant medication to treat GI symptoms (secondary end point). Efficacy was determined by patient-reported global assessment of disease status and the Australian/Canadian Osteoarthritis Hand Index, as well as discontinuations due to lack of efficacy. Patients were evaluated at baseline and at weeks 6 and 12.
Rates of cumulative discontinuation due to GI adverse events were statistically significantly lower in the rofecoxib group than in the naproxen group (5.9% vs. 8.1%; relative risk, 0.74 [95% CI, 0.60 to 0.92]; P = 0.005), as were rates of cumulative use of medication to treat GI symptoms (9.1% vs. 11.2%; relative risk, 0.79 [CI, 0.66 to 0.96]; P = 0.014]). Subgroup analysis of patients who used low-dose aspirin (13%) and those who previously discontinued using arthritis medication because of GI symptoms (15%) demonstrated a relative risk similar to the overall sample for discontinuation due to GI adverse events (relative risk, 0.56 [CI, 0.31 to 1.01] and 0.53 [CI, 0.34 to 0.84], respectively). No statistically significant difference was observed between treatments for efficacy in treating osteoarthritis or for occurrence of other adverse events.
In patients with osteoarthritis treated for 12 weeks, rofecoxib, 25 mg/d, was as effective as naproxen, 500 mg twice daily, but had statistically significantly superior GI tolerability and led to less use of concomitant GI medications. Benefits of rofecoxib in subgroup analyses were consistent with findings in the overall sample.
非甾体抗炎药（NSAIDs）对环氧化酶（COX）-1和COX-2的双重抑制所介导的胃肠道（GI）毒性可导致黏膜完整性的严重改变，或更常见的是导致无法耐受的胃肠道症状，这可能需要停药。与NSAIDs不同，罗非昔布仅作用于COX-2亚型。
评估罗非昔布与萘普生治疗骨关节炎的耐受性。
随机对照试验。
600个门诊和临床研究地点。
5557例患者（平均年龄63岁），基线诊断为膝、髋、手或脊柱骨关节炎。
罗非昔布，25mg/天，或萘普生，500mg，每日两次。允许使用包括阿司匹林在内的常规药物。
因胃肠道不良事件停药（主要终点）和使用辅助药物治疗胃肠道症状（次要终点）。疗效通过患者报告的疾病状态整体评估、澳大利亚/加拿大骨关节炎手部指数以及因缺乏疗效而停药来确定。在基线以及第6周和第12周对患者进行评估。
罗非昔布组因胃肠道不良事件导致的累积停药率在统计学上显著低于萘普生组（5.9%对8.1%；相对风险，0.74[95%CI，0.60至0.92]；P = 0.005），治疗胃肠道症状的药物累积使用率也是如此（9.1%对11.2%；相对风险，0.79[CI，0.66至0.96]；P = 0.014）。对使用低剂量阿司匹林的患者（13%）和之前因胃肠道症状停用关节炎药物的患者（15%）进行亚组分析，结果显示因胃肠道不良事件停药的相对风险与总体样本相似（相对风险分别为0.56[CI，0.31至1.01]和0.53[CI，0.34至0.84]）。在治疗骨关节炎的疗效或其他不良事件的发生方面，两种治疗方法之间未观察到统计学上的显著差异。
在接受12周治疗的骨关节炎患者中，罗非昔布25mg/天与萘普生500mg每日两次疗效相当，但在胃肠道耐受性方面在统计学上显著更优，且使用辅助胃肠道药物的情况更少。罗非昔布在亚组分析中的益处与总体样本的结果一致。
