Panova Elena, Jones Graeme
Menzies Research Institute, Private Bag 23, Hobart, TAS, 7000, Australia.
Drug Saf. 2015 Mar;38(3):245-52. doi: 10.1007/s40264-015-0266-z.
Osteoarthritis (OA) is the leading musculoskeletal cause of disability. Despite this, there is no consensus on the precise definition of OA and what is the best treatment to improve symptoms and slow disease progression. Current pharmacological treatments include analgesics, non-steroidal anti-inflammatory drugs (NSAIDs) and cyclooxygenase (COX) inhibitors. None of those treatments are disease-modifying agents that target the core pathological processes in OA. Diacerein, a semi-synthetic anthraquinone derivative, inhibits the interleukin-1-beta (IL-1β) cytokine which, according to animal studies, plays a key role in the pathogenesis of OA. Diacerein was synthesized in 1980 and licensed in some European Union and Asian countries for up to 20 years. It has shown modest efficacy and acceptable tolerability in a number of trials of low to moderate quality. Early this year, the European Medicines Agency (EMA) conducted a review and restricted the use of diacerein-containing medicines. This was because of major concerns about the frequency and severity of diarrhoea and liver disorders in OA patients. In addition, the EMA's Pharmacovigilance Risk Assessment Committee (PRAC) questioned the limited clinical benefits of diacerein, which, in their view, did not outweigh its risks. The aim of this review is to provide a benefit-risk assessment of diacerein in the treatment of OA, based on asystematic evaluation of the published efficacy and safety data. Overall, there is evidence that diacerein is modestly effective for symptoms and possibly for radiographic changes, but this needs to be balanced against higher rates of gastrointestinal toxicity.
骨关节炎（OA）是导致残疾的主要肌肉骨骼疾病。尽管如此，对于OA的精确定义以及改善症状和减缓疾病进展的最佳治疗方法尚无共识。目前的药物治疗包括镇痛药、非甾体抗炎药（NSAIDs）和环氧化酶（COX）抑制剂。这些治疗方法均不是针对OA核心病理过程的疾病修饰药物。双醋瑞因是一种半合成蒽醌衍生物，可抑制白细胞介素-1-β（IL-1β）细胞因子，根据动物研究，该细胞因子在OA发病机制中起关键作用。双醋瑞因于1980年合成，并在一些欧盟国家和亚洲国家获得了长达20年的许可。在一些质量低至中等的试验中，它显示出一定的疗效和可接受的耐受性。今年早些时候，欧洲药品管理局（EMA）进行了一项审查，并限制了含双醋瑞因药物的使用。这是因为对OA患者腹泻和肝脏疾病的发生率和严重程度存在重大担忧。此外，EMA的药物警戒风险评估委员会（PRAC）质疑双醋瑞因有限的临床益处，他们认为其益处并未超过风险。本综述的目的是基于对已发表的疗效和安全性数据的系统评价，对双醋瑞因治疗OA进行获益-风险评估。总体而言，有证据表明双醋瑞因对症状和可能的影像学改变有一定疗效，但这需要与更高的胃肠道毒性发生率相权衡。
