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PubMed Central, and the Cochrane Central Register of Controlled Trials from inception to December 2019 and sought unpublished data.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.