Schnitzer Thomas J, Weaver Arthur L, Polis Adam B, Petruschke Richard A, Geba Gregory P
Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.
J Rheumatol. 2005 Jun;32(6):1093-105.
To compare efficacy among 1578 patients with osteoarthritis randomized to take acetaminophen 4000 mg (n=269), celecoxib 200 mg (n=523), rofecoxib 12.5 mg (n=259), or rofecoxib 25 mg (n=527) in a double blind trial [Vioxx, Acetaminophen, Celecoxib Trial (VACT2)]. Results were also pooled with the similarly designed VACT1 trial.
Patients evaluated over Days 1 to 6 and 6 weeks with Patient Global Assessment of Response to Therapy (PGART) and Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index.
For VACT2, median time to good or excellent PGART response was 6, 5, 4, and 3 days for acetaminophen, celecoxib, rofecoxib 12.5 mg, and rofecoxib 25 mg (COX-2 inhibitors vs acetaminophen, p<or=0.035; rofecoxib 25 mg vs celecoxib, p=0.01). WOMAC response over the first 6 days was greater (p < 0.05) with both rofecoxib doses than acetaminophen and celecoxib. At Week 6, all COX-2 inhibitors provided significantly greater efficacy than acetaminophen. Good or excellent PGART was numerically, but not significantly, greater with rofecoxib 25 mg (55.4%) than celecoxib (50.6%) at Week 6; a significant difference was seen at Weeks 2 (6.9, p=0.022) and 4 (6.7, p=0.027) and over 6 weeks with analysis of all 5 PGART categories of response (p=0.035). Rofecoxib 25 mg provided greater response (p<0.05) than celecoxib on WOMAC subscales. Pooled analysis of VACT1/VACT2 demonstrated greater PGART (p=0.023) with rofecoxib 25 mg (56.1%) than celecoxib (49.8%) at 6 weeks and greater response to all other PGART and WOMAC endpoints, and confirmed superiority of COX-2 inhibitors to acetaminophen. Overall, tolerability of the study medications was generally good and similar. There was no significant difference between treatment groups in the percentage of patients who experienced a clinical adverse experience (AE). The incidence of discontinuations due to an AE was significantly lower with celecoxib (2.5%) compared to rofecoxib 25 mg (6.3%, p=0.004) or acetaminophen (7.8%, p< 0.001), and did not differ significantly from rofecoxib 12.5 mg (4.6%). Discontinuation rates due to edema and hypertension related AE were similar among all COX-2 inhibitors.
Rofecoxib and celecoxib provided superior efficacy to acetaminophen. There was a more rapid and greater response with rofecoxib 25 mg than celecoxib 200 mg. Rofecoxib 12.5 mg demonstrated greater efficacy than celecoxib 200 mg over the first 6 days, and was similar over 6 weeks. All study medications were generally well tolerated.
在一项双盲试验[万络、对乙酰氨基酚、塞来昔布试验（VACT2）]中，比较1578例骨关节炎患者随机服用4000毫克对乙酰氨基酚（n = 269）、200毫克塞来昔布（n = 523）、12.5毫克罗非昔布（n = 259）或25毫克罗非昔布（n = 527）的疗效。结果还与设计相似的VACT1试验进行了汇总分析。
在第1至6天以及6周时，采用患者对治疗反应的整体评估（PGART）和西安大略和麦克马斯特大学骨关节炎指数（WOMAC）对患者进行评估。
对于VACT2，对乙酰氨基酚、塞来昔布、12.5毫克罗非昔布和25毫克罗非昔布达到良好或优秀PGART反应的中位时间分别为6天、5天、4天和3天（COX-2抑制剂与对乙酰氨基酚相比，p≤0.035；25毫克罗非昔布与塞来昔布相比，p = 0.01）。在最初6天内，两种罗非昔布剂量的WOMAC反应均比对乙酰氨基酚和塞来昔布更大（p < 0.05）。在第6周时，所有COX-2抑制剂的疗效均显著优于对乙酰氨基酚。在第6周时，25毫克罗非昔布（55.4%）的良好或优秀PGART在数值上高于塞来昔布（50.6%），但差异无统计学意义；在第2周（6.9，p = 0.022）和第4周（6.7，p = 0.027）以及对所有5个PGART反应类别进行6周分析时（p = 0.035），差异具有统计学意义。在WOMAC子量表上，25毫克罗非昔布的反应比对塞来昔布更大（p < 0.05）。VACT1/VACT2的汇总分析表明，在6周时，25毫克罗非昔布（56.1%）的PGART高于塞来昔布（49.8%）（p = 0.023），并且对所有其他PGART和WOMAC终点的反应更大，证实了COX-2抑制剂比对乙酰氨基酚更具优势。总体而言，研究药物的耐受性普遍良好且相似。各治疗组中经历临床不良事件（AE）的患者百分比无显著差异。与25毫克罗非昔布（6.3%，p = 0.004）或对乙酰氨基酚（7.8%，p < 0.001）相比，塞来昔布因AE导致停药的发生率显著更低（2.5%），与12.5毫克罗非昔布（4.6%）无显著差异。所有COX-2抑制剂因水肿和高血压相关AE导致的停药率相似。
罗非昔布和塞来昔布的疗效优于对乙酰氨基酚。25毫克罗非昔布比200毫克塞来昔布的反应更快且更大。12.5毫克罗非昔布在最初6天内的疗效优于200毫克塞来昔布，在6周时相似。所有研究药物的耐受性总体良好。
