艾瑞昔布片治疗膝骨关节炎的Ⅱ期多中心随机双盲临床试验

A Multicenter,Double-Blind and Randomized Controlled PhaseⅡtrial of Imrecoxib in Treatment of Knee Osteoarthritis

目的评价艾瑞昔布治疗膝膝骨关节炎(OA)的有效性和安全性。方法采用多中心、随机、双盲、阳性药物平行对照研究试验设计,试验组病人分为A组(72例)、B组(71例)、C组(71例),分别口服艾瑞昔布50 mg bid、100 mg bid和200 mgbid。对照组为D组(70例)口服塞来昔布200 mg qd,疗程12周。观察治疗前及服药后2、4、8、12周患者膝关节活动痛、15周行走时间(s)、健康状况问卷(HAQ)、病人及医师对目前疾病状况的总体评价。主要疗效指标为有效率、总有效率。次要疗效指标为各个单个疗效指标的改善程度。同时观察药物治疗期间发生的不良事件。结果全分析集(FAS)分析提示经过2周治疗后,4组病人总有效率分别达到27.94%、29.69%、30.77%和42.86%(P=0.063 2);治疗满4周时,4组病人总有效率分别达到51.47%、50.00%、52.31%、65.08%(P=0.114 0);治疗满8周时,4组病人总有效率分别达到58.82%、64.06%、64.62%、74.60%(P=0.062 7),治疗满12周时总有效率可分别达到69.12%、64.06%、75.38%和74.60%(P=0.271 9)。4组临床不良反应发生率:A组15/68(22.06%),B组18/65(27.69%),C组21/66(31.82%),D组27/65(41.54%),4组间差异无统计学意义(P=0.103 0)。研究期间A组发生1例严重不良事件(缺血性结肠炎)。B组和D组各发现1例胃/十二指肠黏膜糜烂灶。D组发现了1例食道糜烂。结论 3个剂量组的艾瑞昔布和塞来昔布(200 mg qd)均可有效和安全地治疗膝骨关节炎,结合各次随访的疗效结果,建议艾瑞布III期临床试验时艾瑞昔布的剂量可采用100 mg bid。

OBJECTIVE To evaluate the efficacy and safety of imrecoxib in treatment of osteoarthritis （OA）. METHODS A muhicenter, double-blind, and randomized controlled phase II trial of imrecoxib in treatment of osteoarthritis was designed. The pa- tients were divided into 4 groups ： trial group A （ n = 72 ）, trial group B C n = 71 ）, trial group C （ n = 71 ） and control group （ group D, n = 70） , were treated with imrecoxib 50 mg bid, imrecoxib 100 mg bid. imrecoxib 200 mg bid and celecoxib 200 mg qd, respectively, for 12 wk. Imrecoxib was produced by Jiangsu Hengrui Medicine Co. , Ltd. , and Celccoxib was produced by Pfizer Pharmaceuticals Limited. Assessments included knee joint pain, 15m walking time, health assessment questionary （HAQ）, patient＇s and physician＇s global assessment of disease activity. The primary efficacy measures included effective rate and total effective rate. Secondary efficacy measures were improvement of single outcome measures. Clinical and laboratory advert reactions of the study drugs were observed in both groups. RESULTS FAS （ Full Analysis Set ） analysis showed that total effective rate were 27.94% , 29.69%, 30. 77% and 42. 86 %, respectively, after 2 weeks treatment. And 69. 12%. 64. 06%, 75.38% and 74. 60%, respectively, after 12 weeks treat- ment in group A, group B, group C and group D. The incidents of adverse reaction were 22.06% ,27.69% ,31.82% ,and 41.54% , respectively, after 12 weeks treatment in group A. group B. group C and group D, showing no significant difference between the 4 groups （P 〉 0.05）. 1 case of ischemic colitis was report as SAE. Gastric and duodenal erosion were observed in both group B and group D, and esophageal erosion was observed in group D. ＇CONCLUSIONS Imrecoxib at 3 dosage and celecoxib are effective and safe in the treatment of OA. Dosage of 100mg bid of imrecoxib was proposal in phase III clinical trial.