Pelletier J P, Yaron M, Haraoui B, Cohen P, Nahir M A, Choquette D, Wigler I, Rosner I A, Beaulieu A D
Centre hospitalier de l'Université de Montréal, Hôpital Notre-Dame, Quebec, Canada.
Arthritis Rheum. 2000 Oct;43(10):2339-48. doi: 10.1002/1529-0131(200010)43:10<2339::AID-ANR23>3.0.CO;2-P.
To evaluate the efficacy and safety of diacerein, a drug with interleukin-1beta--inhibitory activity in vitro, in patients with knee osteoarthritis (OA).
A total of 484 patients fulfilling the American College of Rheumatology criteria for knee OA were enrolled in this 16-week, randomized, double-blind, placebo-controlled, parallel study group with 3 diacerein dosages of 50 mg/day, 100 mg/day, and 150 mg/day (administered twice daily).
In the intent-to-treat population, 100 mg/day diacerein (50 mg twice daily) was significantly superior (P < 0.05) to placebo using the primary criterion (visual analog scale [VAS] assessment of pain on movement). Significant improvement (P < 0.05) was also observed for the secondary criteria, which included the Western Ontario and McMaster Universities OA Index (WOMAC), the WOMAC subscores, and the VAS assessment of handicap. In patients treated with diacerein dosages of 50 mg/day and 150 mg/day, favorable but not significant results were observed for the primary criterion. The best daily dosage of diacerein, calculated from the effect on the VAS assessment of pain on movement, was 90.1 mg. In the per-protocol population, the analysis of the primary criterion showed significant dose-dependent differences (P < 0.05) between each of the 3 diacerein dosages and the placebo. No differences were observed among the 3 diacerein groups. A significantly higher incidence (P < 0.05) of adverse events (AEs), as well as a higher rate of dropoout due to AEs, was observed in patients treated with 150 mg/day diacerein versus those treated with placebo, 50 mg/day diacerein, or 100 mg/day diacerein. Mild-to-moderate transient changes in bowel habits were the most frequent AEs, increasing with the dosage.
Diacerein, a drug for the treatment of OA, was shown to be an effective treatment for symptoms in patients with knee OA. Taking into account both efficacy and safety, the optimal daily dosage of diacerein for patients with knee OA is 100 mg/day (50 mg twice daily).
评估双醋瑞因（一种在体外具有白细胞介素-1β抑制活性的药物）对膝骨关节炎（OA）患者的疗效和安全性。
本研究为一项为期16周的随机、双盲、安慰剂对照、平行研究，共纳入484例符合美国风湿病学会膝OA标准的患者，分为3个双醋瑞因剂量组，分别为50毫克/天、100毫克/天和150毫克/天（每日给药两次）。
在意向性分析人群中，采用主要标准（运动时疼痛的视觉模拟评分[VAS]评估），100毫克/天双醋瑞因（每日两次，每次50毫克）显著优于安慰剂（P<0.05）。次要标准（包括西安大略和麦克马斯特大学骨关节炎指数[WOMAC]、WOMAC子评分以及功能障碍的VAS评估）也观察到显著改善（P<0.05）。在接受50毫克/天和150毫克/天双醋瑞因治疗的患者中，主要标准显示出良好但不显著的结果。根据对运动时疼痛的VAS评估效果计算，双醋瑞因的最佳日剂量为90.1毫克。在符合方案人群中，主要标准分析显示，3种双醋瑞因剂量组与安慰剂之间存在显著的剂量依赖性差异（P<0.05）。3个双醋瑞因组之间未观察到差异。与接受安慰剂、50毫克/天双醋瑞因或100毫克/天双醋瑞因治疗的患者相比，接受150毫克/天双醋瑞因治疗的患者不良事件（AE）发生率显著更高（P<0.05），因AE导致的退出率也更高。轻度至中度的排便习惯短暂改变是最常见的AE，且随剂量增加而增加。
双醋瑞因作为一种治疗OA的药物，对膝OA患者的症状显示出有效治疗作用。综合疗效和安全性考虑，膝OA患者双醋瑞因的最佳日剂量为100毫克/天（每日两次，每次50毫克）。
