依托考昔治疗中国人群骨关节炎的临床研究

The clinical study of etoricoxib in the treatment of Chinese patients with osteoarthritis

目的评价依托考昔治疗中国人群膝或髋关节骨关节炎患者的疗效和安全性。方法在该多中心、随机双盲、活性药物平行对照的临床研究中，符合人选标准的患者随机进入试验组（90例，口服依托考昔60mg，每日1次），活性药物对照组（90例，口服双氯芬酸钠缓释片75mg／O2，每日2次）。疗程4周。主要疗效终点为治疗后2组的西安大略大学和麦克马斯特大学骨关节炎指数（WOMAC）疼痛评分。次要疗效终点包括WOMAC进行日常活动的难度评分、WOMAC关节僵硬评分、患者对治疗反应的综合评价（PGART）、研究者对疾病状况的综合评估（IGADS）、因治疗无效而终止研究的情况以及为缓解症状服用的对乙酰氨基酚（扑热息痛片）计数。通过体格检查、实验室检查等评估用药的安全眭。主要统计学方法采用方案分析集（PP）和全分析集（FAS）。结果治疗4周后，2组的WOMAC疼痛评分均较用药前有显著改善，依托考昔组：51±16与21±19；双氯芬酸钠组：53±16与22±19（P〈0．01），但组间比较差异无统计学意义。2组的WOMAC进行日常活动的难度评分、WOMAC关节僵硬评分、PGART、IGADS较用药前均有显著改善（P均〈0．01），但组间比较差异无统计学意义。研究过程中未发生药物相关的严重不良事件。2组药物之间总的药物相关不良事件发生率差异无统计学意义。2种药物的安全眭和耐受性良好。结论依托考昔60mg每日1次能够有效缓解骨关节炎患者的临床症状和体征。该结果在各项评价指标中均得到证实。依托考昔的疗效不劣于双氯芬酸钠缓释片75mg每天2次的疗效。在连续4周治疗期内，依托考昔总体安全性和耐受性良好。

Objective To compare the clinical response with etoricoxib 60 mg once daily with diclofenac sodium tablet 75 mg two times daily in the treatment of osteoarthritis of the knee or hip joint. Methods A 4-week muhicenter, randomized, double-blinded and active comparator-controlled clinical trial was performed during January 2005 and June 2005 in 6 medical centers in China. Eligible patients （≥40 years old Chinese patients with osteoarthritis of the knee and hip） were randomized （1：1 ratio） to receive etoricoxib 60 mg once daily （n=90）, or diclofenac sodium 75 mg twice daily （n=90）. Primary efficacy end point is the change of WOMAC （Western Ontario and McMaster Universities osteoarthritis index） pain subscale from baseline to 4 weeks; non-inferiority bounds were pre-defined [if the upper bound of 95% confidence interval （CI） for the difference is less than 10 mm on a 100-mm VAS WOMAC pain subscale] for the comparison of the change between the two groups. The secondary efficacy endpoints include WOMAC physical function subscale, WOMAC stiffness subscale, patient＇s global assessment of response to therapy （PGART）, investigator＇s global assessment of disease status （IGADS）, discontinuation due to lack of efficacy and rescue paracetamol tablet count. Safety was assessed by physical examination, adverse experience reported, and laboratory safety data. Results Compared to baseline, the changes of WOMAC pain subscale after 4 weeks treatment were statistically significant （P〈0.01） in both groups （etoricoxib group： 51_＋16 vs 21＋ 19; diclofenac sodium group- 53_＋16 vs 22_＋19）. There was no difference in the change of WOMAC pain subscale between the two groups. The change in WOMAC stiffness subscale, WOMAC physical function subscale, PGART and IGADS in both groups were statistically significant （P〈0.01）, but there was no difference between treatment groups according to the pre-defined non-inferiority criteria. No drug related serious adverse events were observed during the study. The difference in drug-related adverse event incidence between the two groups was not statistically significant. Etoricoxib and diclofenac sodium were generally safe and well tolerated. Conclusion Etoricoxib 60 mg administered once daily is efficacious and shows clinical efficacy notinferior to that of diclofenac sodium 75 mg administered twice daily for the treatment of osteoarthritis. Etoricoxib 60 mg administered once daily for 4 weeks is generally safe and well tolerated.