Efficacy, tolerability, and dose-dependent effects of opioid analgesics for osteoarthritis : systematic review and meta-analysis

Objective: Opioids are commonly prescribed for osteoarthritis. Guidelines provide inconsistent recommendations on use of opioids in osteoarthritis and previous reviews are limited in scope, warranting a comprehensive assessment of the evidence. This study evaluated the efficacy and safety of opioids for osteoarthritis. Design: Systematic Review and Meta-Analysis Data Sources: MEDLINE, EMBASE, CINAHL, PsycINFO, CENTRAL, International Clinical Trials Registries (to October 2020). Eligibility Criteria: Randomised placebo-controlled trials evaluating any opioid analgesic for osteoarthritis. Data Extraction and Synthesis: The primary outcome was pain at the medium term (≥6 weeks but <12 months). Continuous pain and disability outcomes were converted to a 0 to 100 scale. Effects <10 points were considered very small. Dichotomous outcomes were presented as risk ratios. Four authors extracted data and assessed risk of bias. Data were pooled using a random effects model. Quality of evidence was assessed using GRADE. Results: Thirty-six trials (dose range: 10-210 oral morphine milligram equivalent units/day) were included. For the medium term, there was low quality evidence from 19 trials (n=8965) of a very small effect of opioids compared to placebo for pain; mean difference (MD) -4.59 (95% CI -7.17, -2.02) and low quality evidence from 16 trials (n=6882) of a very small effect on disability; MD -4.15 (95% CI -6.94, -1.35). Meta-regression didn’t show a significant association of dose with adverse events or pain relief. Opioids increased the risk of adverse events; RR: 1.43 (1.29, 1.59), but evidence was of very low quality. There were no long-term outcomes data. Conclusions: For people with osteoarthritis, opioids may provide very small effects on pain and disability, and may increase the risk of adverse events. Registration: CRD42019142813.