Objectives

To quantify the placebo effect of intraarticular injections for knee osteoarthritis in terms of pain, function, and objective outcomes. Factors influencing placebo effect were investigated.

Design

Meta-analysis of randomized controlled trials; Level of evidence, 2. PubMed, Web of Science, Cochrane Library, and grey literature databases were searched on January 8, 2020, using the string: (knee) AND (osteoarthritis OR OA) AND (injections OR intra-articular) AND (saline OR placebo). The following inclusion criteria were used: double-blind, randomized controlled trials on knee osteoarthritis, including a placebo arm on saline injections. The primary outcome was pain variation. Risk of bias was assessed using the RoB 2.0 tool, and quality of evidence was graded following the GRADE (Grading of Recommendations Assessment, Development and Evaluation) guidelines.

Results

Out of 2,363 records, 50 articles on 4,076 patients were included. The meta-analysis showed significant improvements up to the 6-month follow-up: Visual Analogue Scale (VAS)-pain −13.4 mean difference (MD) (95% confidence interval [CI]: −21.7/−5.1; P < 0.001), Western Ontario and McMaster Osteoarthritis Index (WOMAC)-pain −3.3 MD (95% CI: −3.9/−2.7; P < 0.001). Other significant improvements were WOMAC-stiffness −1.1 MD (95% CI: −1.6/−0.6; P < 0.001), WOMAC-function −10.1 MD (95% CI: −12.2/−8.0; P < 0.001), and Evaluator Global Assessment −21.4 MD (95% CI: −29.2/−13.6; P < 0.001). The responder rate was 52% (95% CI: 40% to 63%). Improvements were greater than the “minimal clinically important difference” for all outcomes (except 6-month VAS-pain). The level of evidence was moderate for almost all outcomes.

Conclusions

The placebo effect of knee injections is significant, with functional improvements lasting even longer than those reported for pain perception. The high, long-lasting, and heterogeneous effects on the scales commonly used in clinical trials further highlight that the impact of placebo should not be overlooked in the research on and management of knee osteoarthritis.

中文翻译：

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“安慰剂注射”对膝关节骨性关节炎的长期影响：荟萃分析

目标

从疼痛、功能和客观结果方面量化关节内注射治疗膝骨关节炎的安慰剂效应。研究了影响安慰剂效应的因素。

设计

随机对照试验的荟萃分析；证据级别，2。PubMed、Web of Science、Cochrane 图书馆和灰色文献数据库于 2020 年 1 月 8 日进行了检索，使用字符串：(膝盖) AND (骨关节炎或 OA) AND (注射或关节内) AND (盐水或安慰剂）。使用了以下纳入标准：关于膝关节骨性关节炎的双盲、随机对照试验，包括注射盐水的安慰剂组。主要结果是疼痛变化。偏倚风险使用 RoB 2.0 工具进行评估，证据质量按照 GRADE（推荐评估、开发和评估分级）指南进行分级。

结果

在 2,363 条记录中，包含 4,076 名患者的 50 篇文章。荟萃分析显示随访 6 个月有显着改善：视觉模拟量表 (VAS)-疼痛 -13.4 平均差 (MD)（95% 置信区间 [CI]：-21.7/-5.1；P < 0.001 )、西安大略和麦克马斯特骨关节炎指数 (WOMAC)-疼痛 -3.3 MD (95% CI: -3.9/-2.7; P < 0.001)。其他显着改善包括 WOMAC 刚度 -1.1 MD（95% CI：-1.6/-0.6；P < 0.001）、WOMAC 功能 -10.1 MD（95% CI：-12.2/-8.0；P < 0.001）和评估器全球评估 -21.4 MD（95% CI：-29.2/-13.6；P< 0.001)。应答率为 52%（95% CI：40% 至 63%）。对于所有结果（除了 6 个月的 VAS 疼痛），改善程度都大于“最小的临床重要差异”。几乎所有结局的证据水平适中。

结论

膝关节注射的安慰剂效应是显着的，其功能改善的持续时间甚至比疼痛感知报告的持续时间更长。临床试验中常用的量表上的高、持久和异质效应进一步强调了安慰剂的影响在膝骨关节炎的研究和管理中不应被忽视。