Diacerein for osteoarthritis.
Diacerein for osteoarthritis.
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DOI：
10.1002/14651858.cd005117
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发表时间：
2006
期刊：
影响因子：
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通讯作者：
Tsa Fidelix;Bgo Soares;Vfm Trevisani
中科院分区：
文献类型：
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作者：
Tsa Fidelix;Bgo Soares;Vfm Trevisani
骨关节炎（OA）是最常见的肌肉骨骼疾病之一。双醋瑞因的作用与传统的非甾体抗炎药（NSAID）不同，后者抑制前列腺素合成，导致不良胃肠道反应。已经提出双醋瑞因作为一种缓慢作用的、改善骨关节炎的药物，并且可能是改善骨关节炎疾病结构的药物。根据美国流变学会和/或EULAR诊断标准，评估双醋瑞因治疗成人外周或轴性骨关节炎的有效性和安全性。检索策略：我们检索了MEDLINE（1966-2004）、EMBASE（1980-2004）、科克伦对照试验中心注册库（CENTRAL）、科克伦图书馆2004年第3期和LILACS（1982-2004），并手工检索了已发表文章的参考文献列表。联系了制药公司和已发表文章的作者。没有语言限制。选择标准符合美国风湿病学会（ACR）标准的双醋瑞因在原发性或继发性OA成人中的安慰剂对照和比较研究的随机对照试验（RCT）或准RCT有资格入选。排除的主要标准是继发性疾病的证据。数据收集和分析数据提取和质量评估由三名研究者根据预先确定的标准独立进行，并将结果进行比较以确定一致程度。使用科克伦手册标准、Jadad和Schultz评分进行质量评价。使用加权平均差（WMD）合并连续结局指标。使用随机效应模型合并二分结局指标，结果表示为相对风险（RR）。总的来说，包括2069名参与者的7项确定的研究证明了双醋瑞因在治疗OA中的小的、一致的、有益的作用。当与安慰剂相比时，在1228名参与者中评估了视觉模拟量表（0-100 mm）上的疼痛，并显示出统计学显著差异，有利于双醋瑞因WMD-5.16（95%CI-9.75，-0.57），量表上的绝对变化为5分;但异质性分析结果很重要（P=0.04）。当按髋关节OA和膝关节OA单独分析时，未检测到差异。根据Lequesne功能损害指数，1006例受试者在整个组或亚组分析中均无改善，所有结果均具有同质性（P>0.10）。对于髋关节OA，3项研究显示WMD为-0.21（95%CI-0.82，0.40）。对于膝关节OA，2项研究显示WMD为-0.95（95%CI-2.64，0.74）。总体WMD为-0.29（95%CI-0.87，0.28）。两项长期研究，一项评价髋关节OA，另一项评价膝关节OA，通过关节间隙的放射学测量分析了结构进展。在髋关节OA中，与膝关节OA相比，进展有统计学显著性减缓，膝关节OA没有表现出这种减缓。然而，两项研究的总体效果差异很大（髋关节OA P=0.04，膝关节OA P= 0.85）。最常见的不良事件是腹泻。在1083名接受双醋瑞因的参与者中，有459名参与者（42%）受到影响。治疗组中有18%的患者因不良事件退出，而安慰剂组中有13%的患者因不良事件退出。专家结论：有“黄金”级证据表明双醋瑞因在改善疼痛方面有小而一致的益处。需要进一步研究以证实双醋瑞因治疗OA的短期和长期有效性和毒性。
BACKGROUND Osteoarthritis (OA) is one of the most prevalent musculoskeletal diseases. Diacerein acts differently from traditional non-steroidal anti-inflammatory drugs (NSAIDs) which inhibit prostaglandin synthesis, leading to adverse gastrointestinal effects. It has been proposed that diacerein acts as a slow-acting, symptom-modifying and perhaps disease-structure modifying drug for OA. OBJECTIVES To assess the effectiveness and safety of diacerein for treatment of OA in adults with peripheral or axial osteoarthritis according the American College of Rheumatology and/or EULAR diagnostic criteria. SEARCH STRATEGY We searched MEDLINE (1966-2004), EMBASE (1980-2004), Cochrane Central Register of Controlled Trials (CENTRAL), The Cochrane Library, Issue 3, 2004, and LILACS(1982-2004) and hand searched reference lists of published articles. Pharmaceutical companies and authors of published articles were contacted. There was no language restriction. SELECTION CRITERIA Randomized controlled trials (RCT) or quasi-RCTs of placebo-controlled and comparative studies of diacerein in adults with primary or secondary OA fulfilling the American College of Rheumatology (ACR) criteria were eligible for inclusion. The main criteria for exclusion was evidence of secondary disease. DATA COLLECTION AND ANALYSIS Data abstraction and quality assessment was performed independently by three investigators according to predetermined criteria and the results were compared to determine the degree of agreement. Quality evaluation was done using Cochrane Handbook Criteria, Jadad and Schultz scores. Continuous outcome measures were pooled using weighted mean differences (WMD). Dichotomous outcome measures were pooled using random effects model and results were expressed as relative risks (RR). MAIN RESULTS Collectively, the seven identified studies including 2069 participants demonstrated a small, consistent, beneficial effect of diacerein in the treatment of OA. When compared to placebo, pain on a visual analog scale (0-100 mm) was evaluated in 1228 participants and showed a statistically significant difference in favour of diacerein WMD -5.16 (95%CI -9.75, -0.57) with an absolute change of 5 points on the scale; but the heterogeneity analysis result was important (P=0.04). When analysed separately by hip OA and knee OA, no difference was detected. According to the Lequesne Impairment Index for function, 1006 participants evaluated did not have improvement in the whole group or in the subgroup analysis with homogeneity in all results (P>0.10). For hip OA, three studies showed a WMD -0.21 (95%CI -0.82, 0.40). For knee OA, two studies showed WMD -0.95 (95%CI -2.64, 0.74). The summary WMD was -0.29 (95%CI -0.87, 0.28). Two long-term studies, one evaluating hip OA and another evaluating knee OA, analysed structural progression with radiographic measurements of joint space. In hip OA, there was statistical significant slowing of progression in contrast with knee OA that did not demonstrate this reduction. However, the overall effect was very different between studies (P=0.04 for hip OA and P= 0.85 for knee OA). The most frequent adverse event was diarrhea. 459 participants among 1083 participants that received diacerein (42%) were affected. 18% in the treatment group compared with 13% in the placebo group withdrew due to adverse events. AUTHORS' CONCLUSIONS There is 'gold' level evidence that diacerein has a small, consistent benefit in improvement in pain. Further research is necessary to confirm the short and long-term effectiveness and toxicity of diacerein therapy in OA.