双醋瑞因治疗膝骨关节炎的疗效与安全性多中心对照研究

Efficacy and safety of diacerein in osteoarthritis of the knee-a multicenter,controlled trial

目的评价双醋瑞因(安必丁)治疗膝骨关节炎(OA)患者的疗效和安全性。方法223例符合美国风湿病学院(ACR)膝OA标准的患者纳入随机、多中心、双氯酚酸钠对照、双模拟研究,双醋瑞因组100mg/d,双氯酚酸钠75mg/d,治疗12周,随访4周。结果经12周治疗,患者/医生评价两组总有效率分别是65.4%/61.6%和61.2%/61.2%(P>0.05)。双醋瑞因组和对照组在主要疗效指标(20m步行痛)和次要疗效指标(关节触痛、WOMAC骨关节炎指数和健康状况调查问卷SF-36)均较治疗前明显改善,随访期(停药1个月后),双醋瑞因能持续发挥药效,以上各项疗效参数较治疗结束时变化不大。但在对照组,随访期与治疗结束时相比,20m步行痛和关节触痛疼痛程度明显加重,WOMAC骨关节炎指数明显增加(P<0.05)。同时,随访期试验组对乙酰氨基酚用量明显低于对照组。出现可能与试验药物相关的不良事件的比例在双醋瑞因组和对照组分别为35.7%和45.1%(P>0.05)。主要为轻至中度的胃肠道反应。结论应用双醋瑞因治疗膝OA疗效与双氯酚酸钠基本相当,而且双醋瑞因的作用更持久,无严重不良反应发生,安全性好。

Objective To evaluate the efficacy and safety of diacerein in patients with knee osteoarthritis (OA). Methods A total of 223 patients fulfilling the American College of Rheumatology criteria for knee OA were enrolled in this 17-week, randomized, double-dummy, diclofenac-controlled trial. The diacerein dosages in this trial was 100 mg/d, and the dosage of diclofenac sodium was 75 mg/day. Results After 12 weeks of treatment, the total efficacy rate of patients′/ physicians global assessment in the diacerein and the diclofenac groups was 65.4%/61.6% and 61.2%/61.2% respectively(P>0.05). In the intent-to-treat population, the primary criterion [visual analog scale (VAS) assessment of pain on walking for 20 metres] was significantly superior(P<0.05) to baseline in both groups. Significant improvement (P<0.05) was also observed for the secondary criteria, which included tenderness on palpation, Western Ontario and McMaster Universities OA index (WOMAC) and Short-Form Health Survey (SF-36). In the follow-up period, there are no obvious changes in the above parameters in the diacerein group. But in the diclofenac group, pain on walking for 20 metres, tenderness on palpation and WOMAC became worsen after withdrawing the drugs for 4 weeks. Moreover, the consumption of paracetamol was significantly lower in the diacerein group than in the diclofenac group during the follow-up period. The incidence of related adverse events was 35.7% in the diacerein and 45.1% in the diclofenac group(P>0.05). Mild-to-moderate gastrointestinal discomfort was the most frequent adverse event. Conclusion Diacerein has been shown to be as effective as diclofenac in treating patients with knee OA, coupled with a carry-over effect. Diacerein has a good safety profile. No severe adverse events has occurred.