Tufts Medical Center, Boston, Massachusetts.
Lund University, Lund, Sweden.
Arthritis Care Res (Hoboken). 2021 Oct;73(10):1413-1424. doi: 10.1002/acr.24363. Epub 2021 Sep 1.
Opioids have long been prescribed for chronic pain conditions, including osteoarthritis (OA). However, there is little information about their temporal efficacy, or differences in efficacy and safety between opioids with strong versus weak/intermediate μ opioid receptor-binding affinity. To explore these research questions, we conducted a systematic review and meta-analyses of randomized controlled trials (RCTs) conducted in patients with knee and/or hip OA.
We searched Medline, Embase, PubMed Central, and the Cochrane Central Register of Controlled Trials from inception to December 2019 and sought unpublished data. Placebo-controlled RCTs of oral opioids in patients with knee and/or hip OA were included. Standardized mean differences (SMDs) were calculated for pain and function at 2, 4, 8, and 12 weeks. Subgroup analyses for strong and weak/intermediate opioids were conducted. Meta-regression was performed to assess the impact of dosage (morphine equivalency) on pain relief. Risk ratios were calculated for safety at the final follow-up.
A total of 18 RCTs (9,283 participants) were included. Opioids demonstrated small benefits on pain at each time point, with SMDs ranging from -0.28 (95% confidence interval [95% CI] -0.38, -0.17) to -0.19 (95% CI -0.29, -0.08); similar effects were observed for function. Strong opioids demonstrated consistently inferior efficacy and overall worse safety than weak/intermediate opioids. Meta-regression revealed that incremental pain relief achieved beyond 20-50-mg doses was not substantial in the context of increased safety risks.
Opioids provide minimal relief of OA symptoms within a 12-week period, and they are known to cause discomfort in a majority of patients. Clinicians and policy makers should reconsider the utility of opioids in the management of OA.
阿片类药物长期以来一直被用于治疗慢性疼痛疾病，包括骨关节炎（OA）。然而，关于它们的时间疗效，以及具有强μ阿片受体结合亲和力与弱/中μ阿片受体结合亲和力的阿片类药物在疗效和安全性方面的差异的信息很少。为了探讨这些研究问题，我们对膝关节和/或髋关节 OA 患者的随机对照试验（RCT）进行了系统评价和荟萃分析。
我们检索了 Medline、Embase、PubMed Central 和 Cochrane 对照试验中心从开始到 2019 年 12 月的数据库，并寻找未发表的数据。纳入了膝关节和/或髋关节 OA 患者口服阿片类药物的安慰剂对照 RCT。计算了疼痛和功能在 2、4、8 和 12 周的标准化均数差（SMD）。对强阿片类药物和弱/中阿片类药物进行了亚组分析。进行了荟萃回归分析，以评估剂量（吗啡等效剂量）对疼痛缓解的影响。在最后一次随访时计算了安全性的风险比。
共纳入 18 项 RCT（9283 名参与者）。阿片类药物在每个时间点均显示出较小的疼痛缓解作用，SMD 范围从-0.28（95%置信区间[95%CI]-0.38，-0.17）到-0.19（95%CI-0.29，-0.08）；功能也有类似的效果。强阿片类药物的疗效始终低于弱/中阿片类药物，且总体安全性更差。荟萃回归显示，在增加安全性风险的情况下，超过 20-50mg 剂量的增量疼痛缓解并不显著。
阿片类药物在 12 周内对 OA 症状的缓解作用很小，而且它们会导致大多数患者不适。临床医生和决策者应重新考虑阿片类药物在 OA 管理中的效用。
