Weaver Arthur L, Messner Ronald P, Storms William W, Polis Adam B, Najarian Daryl K, Petruschke Richard A, Geba Gregory P, Tershakovec Andrew M
University of Nebraska Medical Center, Omaha, Nebraska, USA.
J Clin Rheumatol. 2006 Feb;12(1):17-25. doi: 10.1097/01.rhu.0000200384.79405.33.
Rofecoxib and nabumetone were developed to provide gastrointestinal benefits over traditional nonsteroidal antiinflammatory drugs (NSAIDs). However, there is limited comparative information relating to these 2 drugs.
The objective of this study was to compare rofecoxib and nabumetone, at their lower, recommended doses, in patients with osteoarthritis (OA).
Nine hundred seventy-eight patients with knee OA and a positive history of NSAID response were randomized to 12.5 mg rofecoxib per day (N=390), nabumetone 500 mg twice a day (N=392), or placebo (N=196) for 6 weeks. The primary efficacy end point was percent of patients with a "good" or "excellent" Patient Global Assessment of Response to Therapy (PGART) at week 6; PGART was also evaluated over days 1 to 6. Additional end points included investigator assessment of response, pain walking over 6 days and 6 weeks, joint tenderness, discontinuation as a result of lack of efficacy, and quality of life. Adverse experiences (AEs) were collected.
Significantly more rofecoxib (50.4%) than nabumetone (43.3%, P=0.043) or placebo (29.5%, P<0.001) patients had a good or excellent PGART at week 6. Median time to a good or excellent PGART was significantly shorter with rofecoxib (52 hours) than nabumetone (100 hours, P=0.001) or placebo (>124 hours, P<0.001). Results for rofecoxib and nabumetone were similar in all additional end points except pain in walking over 6 days and 6 weeks, in both of which the rofecoxib treatment group demonstrated better results. There were significantly (P<0.050) more overall and serious AEs and discontinuations resulting from AEs with rofecoxib than nabumetone. Five rofecoxib and one nabumetone patients had confirmed thrombotic cardiovascular events (P=0.123). Information on thrombotic cardiovascular events from this study was included in a published, prespecified pooled analysis and is included here for completeness.
At their recommended starting doses for OA, both agents were more effective than placebo. Rofecoxib at a dosage of 12.5 mg demonstrated significantly better efficacy in PGART than 1000 mg nabumetone in these patients known to be NSAID responders. Significantly more AEs occurred with rofecoxib than nabumetone. Considering these data and other recent safety information regarding cyclooxygenase-2 selective and nonselective NSAIDS, physicians must make risk/benefit assessments for each individual patient when considering the use of these agents, as recommended by the U.S. Food and Drug Administration.
研发罗非昔布和萘丁美酮是为了比传统非甾体抗炎药（NSAIDs）在胃肠道方面更具优势。然而，关于这两种药物的比较信息有限。
本研究的目的是比较罗非昔布和萘丁美酮在骨关节炎（OA）患者中的较低推荐剂量。
978例有NSAIDs反应阳性史的膝骨关节炎患者被随机分为每日服用12.5mg罗非昔布组（N = 390）、每日两次服用500mg萘丁美酮组（N = 392）或安慰剂组（N = 196），为期6周。主要疗效终点是第6周时患者对治疗反应的总体评估（PGART）为“良好”或“优秀”的患者百分比；在第1至6天也对PGART进行了评估。其他终点包括研究者对反应的评估、6天和6周内行走时的疼痛、关节压痛、因疗效不佳而停药以及生活质量。收集不良事件（AE）。
在第6周时，罗非昔布组（50.4%）有良好或优秀PGART的患者显著多于萘丁美酮组（43.3%，P = 0.043）或安慰剂组（29.5%，P < 0.001）。达到良好或优秀PGART的中位时间，罗非昔布组（52小时）显著短于萘丁美酮组（100小时，P = 0.001）或安慰剂组（>124小时，P < 0.001）。除了6天和6周行走时的疼痛外，罗非昔布和萘丁美酮在所有其他终点的结果相似，在这两个方面罗非昔布治疗组均表现出更好的结果。罗非昔布组因AE导致的总体和严重AE以及停药显著多于萘丁美酮组（P < 0.050）。5例罗非昔布患者和1例萘丁美酮患者确诊有血栓性心血管事件（P = 0.123）。本研究中关于血栓性心血管事件的信息已包含在已发表的、预先指定的汇总分析中，此处为完整性而纳入。
在OA的推荐起始剂量下，两种药物均比安慰剂更有效。在这些已知对NSAIDs有反应的患者中，12.5mg剂量的罗非昔布在PGART方面的疗效显著优于1000mg萘丁美酮。罗非昔布出现的AE显著多于萘丁美酮。考虑到这些数据以及最近关于环氧化酶-2选择性和非选择性NSAIDs的其他安全信息，医生在考虑使用这些药物时，必须如美国食品药品监督管理局所建议的，对每个患者进行风险/效益评估。
