Baraf Herbert S B, Gold Morris S, Petruschke Richard A, Wieman Matthew S
Center for Rheumatology and Bone Research, a division of Arthritis and Rheumatism Associates, PC, Wheaton, Maryland, USA.
Am J Geriatr Pharmacother. 2012 Feb;10(1):47-60. doi: 10.1016/j.amjopharm.2011.12.002. Epub 2012 Jan 20.
Nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with a dose-related risk of cardiovascular, renal, and gastrointestinal adverse events (AEs). Topical NSAIDs produce lower systemic NSAID exposure compared with oral NSAIDs, offering potential benefits.
To evaluate the safety of topical diclofenac sodium 1% gel (DSG) for knee and hand osteoarthritis (OA) in older and younger patients and in patients with versus without comorbid hypertension, type 2 diabetes, or cerebrovascular or cardiovascular disease.
Post hoc analysis of pooled data from 5 randomized, double-blind, placebo-controlled trials involving 1426 patients (aged ≥35 years) with mild to moderate OA of the knee and 783 patients (aged ≥40 years) with mild to moderate OA of the hand. Patients applied 4 g of DSG or vehicle to affected knees QID for 12 weeks or 2 g of DSG or vehicle to affected hands QID for 8 weeks.
In patients with knee OA, the percentage with ≥1 adverse event was similar in patients aged <65 years (56.6%) versus ≥65 years (55.8%) and was similar in patients with versus without comorbid hypertension (53.4% vs 59.0%, respectively), type 2 diabetes mellitus (50.0% vs 57.2%), or cerebrovascular or cardiovascular disease (53.8% vs 56.5%). In patients with hand OA, the percentage with ≥1 AE was similar in patients aged ≥65 years (42.7%) versus <65 years (39.1%) and was similar in patients with versus without hypertension (39.6% vs 41.7%, respectively), lower in patients with versus without type 2 diabetes mellitus (28.0% vs 41.6%), and higher in patients with versus without cerebrovascular or cardiovascular disease (48.5% vs 39.2%). Gastrointestinal, cardiovascular, and renal AEs were rare and did not differ according to age or comorbidity. Application site reactions were the primary cause for the greater frequency of AEs with DSG versus vehicle.
The similar and low rates of AEs in DSG-treated patients aged ≥65 years and <65 years and in those with and without comorbid hypertension, type 2 diabetes, or cerebrovascular or cardiovascular disease suggest that DSG treatment is generally well tolerated.
非甾体抗炎药（NSAIDs）与心血管、肾脏和胃肠道不良事件（AE）的剂量相关风险有关。与口服NSAIDs相比，外用NSAIDs产生的全身NSAIDs暴露较低，具有潜在益处。
评估1%双氯芬酸钠凝胶（DSG）用于老年和年轻患者以及伴有或不伴有合并症（高血压、2型糖尿病、脑血管或心血管疾病）的膝骨关节炎（OA）和手骨关节炎患者的安全性。
对5项随机、双盲、安慰剂对照试验的汇总数据进行事后分析，这些试验涉及1426例年龄≥35岁的膝部轻至中度OA患者和783例年龄≥40岁的手部轻至中度OA患者。患者将4g DSG或赋形剂每日4次涂抹于患膝，持续12周，或将2g DSG或赋形剂每日4次涂抹于患手，持续8周。
在膝OA患者中，年龄<65岁的患者（56.6%）与年龄≥65岁的患者（55.8%）中发生≥1次不良事件的百分比相似，伴有和不伴有合并症（高血压、2型糖尿病、脑血管或心血管疾病）的患者中该百分比也相似（分别为53.4%和59.0%、50.0%和57.2%、53.8%和56.5%）。在手部OA患者中，年龄≥65岁的患者（42.7%）与年龄<65岁的患者（39.1%）中发生≥1次AE的百分比相似，伴有和不伴有高血压的患者中该百分比也相似（分别为39.6%和41.7%），伴有2型糖尿病的患者中该百分比低于不伴有2型糖尿病的患者（28.0%和41.6%），伴有脑血管或心血管疾病的患者中该百分比高于不伴有脑血管或心血管疾病的患者（48.5%和39.2%）。胃肠道、心血管和肾脏AE罕见，且在年龄或合并症方面无差异。应用部位反应是DSG组比赋形剂组AE发生率更高的主要原因。
在年龄≥65岁和<65岁以及伴有和不伴有合并症（高血压、2型糖尿病、脑血管或心血管疾病）的DSG治疗患者中，AE发生率相似且较低，这表明DSG治疗总体耐受性良好。
