Bellamy N, Campbell J, Robinson V, Gee T, Bourne R, Wells G
University of Queensland, Centre Of National Research On Disability And Rehabilitation Medicine, Level 3, Mayne Medical School, Herston Road, Brisbane, Queensland, Australia, 4006.
Cochrane Database Syst Rev. 2006 Apr 19(2):CD005328. doi: 10.1002/14651858.CD005328.pub2.
Osteoarthritis (OA) is a common joint disorder. In the knee, injections of corticosteroids into the joint (intraarticular (IA)) may relieve inflammation, and reduce pain and disability.
To evaluate the efficacy and safety of IA corticosteroids in treatment of OA of the knee.
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 2, 2003), MEDLINE (to January (week 1) 2006 for update), EMBASE, PREMEDLINE (all to July 2003), and Current Contents (Sept 2000). Specialised journals, trial reference lists and review articles were handsearched.
Randomised controlled trials of IA corticosteroids for patients with OA of the knee: single/double blind, placebo-based/comparative studies, reporting at least one core OMERACT III outcome measure.
Methodological quality of trials was assessed, and data were extracted in duplicate. Fixed effect and random effects models, giving weighted mean differences (WMD), were used for continuous variables. Dichotomous outcomes were analysed by relative risk (RR).
Twenty-eight trials (1973 participants) comparing IA corticosteroid against placebo, against IA hyaluronan/hylan (HA products), against joint lavage, and against other IA corticosteroids, were included.IA corticosteroid was more effective than IA placebo for pain reduction (WMD -21.91; 95% confidence interval (CI) -29.93 to -13.89) and patient global assessment (the RR was 1.44 (95% CI 1.13 to 1.82)) at one week post injection with an NNT of 3 to 4 for both, based on n=185 for pain on 100 mm visual analogue scale (VAS) and n=158 for patient global assessment. Data on function were sparse at one week post injection and neither statistically significant nor clinically important differences were detected. There was evidence of pain reduction between two weeks (the RR was 1.81 (95% CI 1.09 to 3.00)) to three weeks (the RR was 3.11 (95% CI 1.61 to 6.01), but a lack of evidence for efficacy in functional improvement. At four to 24 weeks post injection, there was lack of evidence of effect on pain and function (small studies showed benefits which did not reach statistical or clinical importance, i.e. less than 20% risk difference). For patient global, there were three studies which consistently showed lack of effect longer than one week post injection. However, all were fairly small sample sizes (less than 50 patients per group). This was supported by another study which did not find statistically significant differences, at any time point, on a continuous measure of patient global assessment (100 mm VAS).In comparisons of corticosteroids and HA products, no statistically significant differences were in general detected at one to four weeks post injection. Between five and 13 weeks post injection, HA products were more effective than corticosteroids for one or more of the following variables: WOMAC OA Index, Lequesne Index, pain, range of motion (flexion), and number of responders. One study showed a difference in function between 14 to 26 weeks, but no differences in efficacy were detected at 45 to 52 weeks. In general, the onset of effect was similar with IA corticosteroids, but was less durable than with HA products. Comparisons of IA corticosteroids showed triamcinolone hexacetonide was superior to betamethasone for number of patients reporting pain reduction up to four weeks post injection (the RR was 2.00 (95% CI 1.10 to 3.63). Comparisons between IA corticosteroid and joint lavage showed no differences in any of the efficacy or safety outcome measures.
AUTHORS' CONCLUSIONS: The short-term benefit of IA corticosteroids in treatment of knee OA is well established, and few side effects have been reported. Longer term benefits have not been confirmed based on the RevMan analysis. The response to HA products appears more durable. In this review, some discrepancies were observed between the RevMan 4.2 analysis and the original publication. These are likely the result of using secondary rather than primary data and the statistical methods available in RevMan 4.2. Future trials should have standardised outcome measures and assessment times, run longer, investigate different patient subgroups, and clinical predictors of response (those associated with inflammation and structural damage).
骨关节炎（OA）是一种常见的关节疾病。在膝关节，关节内注射皮质类固醇（IA）可缓解炎症，减轻疼痛和残疾。
评估关节内注射皮质类固醇治疗膝关节OA的疗效和安全性。
我们检索了Cochrane对照试验中心注册库（CENTRAL）（2003年第2期）、MEDLINE（至2006年1月第1周进行更新）、EMBASE、PREMEDLINE（均至2003年7月）以及《现刊目次》（2000年9月）。对手检了专业期刊、试验参考文献列表和综述文章。
膝关节OA患者关节内注射皮质类固醇的随机对照试验：单盲/双盲、基于安慰剂/比较性研究，报告至少一项OMERACT III核心结局指标。
评估试验的方法学质量，数据提取一式两份。连续变量采用固定效应和随机效应模型，给出加权均数差值（WMD）。二分结局采用相对危险度（RR）分析。
纳入了28项试验（1973名参与者），比较关节内注射皮质类固醇与安慰剂、与关节内透明质酸/透明质烷（HA产品）、与关节灌洗以及与其他关节内注射皮质类固醇。关节内注射皮质类固醇在注射后1周时比关节内注射安慰剂在减轻疼痛方面更有效（WMD -21.91；95%置信区间（CI）-29.93至-13.89），在患者整体评估方面也更有效（RR为1.44（95%CI 1.13至1.82）），两者的NNT均为3至4，基于100mm视觉模拟量表（VAS）上疼痛的n = 185例和患者整体评估的n = 158例。注射后1周时功能数据较少，未检测到统计学上显著或临床上重要的差异。有证据表明在注射后2周（RR为1.81（95%CI 1.09至3.00））至3周（RR为3.11（95%CI 1.61至6.01））疼痛减轻，但缺乏功能改善疗效的证据。在注射后4至24周，缺乏对疼痛和功能有影响的证据（小型研究显示有获益，但未达到统计学或临床重要性，即风险差异小于20%）。对于患者整体评估，有3项研究一致显示注射后1周以上无效果。然而，所有研究样本量都相当小（每组少于50例患者）。另一项研究支持了这一点，该研究在患者整体评估的连续测量（100mm VAS）上，在任何时间点均未发现统计学上显著的差异。在皮质类固醇与HA产品的比较中，注射后1至4周一般未检测到统计学上显著的差异。在注射后5至13周，HA产品在以下一个或多个变量上比皮质类固醇更有效：WOMAC OA指数、Lequesne指数、疼痛、活动范围（屈曲）和反应者数量。一项研究显示在14至26周功能有差异，但在45至52周未检测到疗效差异。一般来说，关节内注射皮质类固醇的起效时间相似，但持续时间比HA产品短。关节内注射皮质类固醇的比较显示，注射后4周内报告疼痛减轻的患者数量上，曲安奈德六乙酸酯优于倍他米松（RR为2.00（95%CI 1.10至3.63））。关节内注射皮质类固醇与关节灌洗的比较显示，在任何疗效或安全性结局指标上均无差异。
关节内注射皮质类固醇治疗膝关节OA的短期益处已得到充分证实，且报告的副作用很少。基于RevMan分析，长期益处尚未得到证实。对HA产品的反应似乎更持久。在本综述中，RevMan 4.2分析与原始出版物之间存在一些差异。这些可能是使用二手而非原始数据以及RevMan 4.2中可用统计方法的结果。未来的试验应具有标准化的结局指标和评估时间，进行更长时间的研究，调查不同的患者亚组以及反应的临床预测因素（与炎症和结构损伤相关的因素）。
