Background: Despite recent therapeutic advances, osteoarthritis continues to be a challenging health
problem, especially in the elderly population. Opioids, which are potent analgesics, have shown an extraordinary
ability to reduce intense pain in many osteoarthritic clinical trials; however, there is an increased need for a study to
integrate the reported outcomes and utilize them to achieve a better understanding. Herein, efficacy and safety
aspects of opioids used to manage osteoarthritic pain were assessed and compared using a model-based meta-analysis
Methods: To perform the analysis, a comprehensive database consisting of pain relief compounds with information
on summary-level of efficacy over time, adverse events and dropout rates was compiled from multiple sources.
MBMA was conducted using a nonlinear mixed-effects modeling approach.
Results: The results of primary efficacy endpoint analysis indicated that the doses of oxycodone, oxymorphone, and
tramadol required to produce 50% of the maximum effect were 47, 84, and 247 mg per day, respectively. Efficacytime
course analysis showed that opioids had rapid time to efficacy onset, suggesting potentially powerful painrelieving
effects. It was also found that gastrointestinal adverse events were the most opioid-associated and dosedependent
adverse effects. In addition, the analysis revealed that opioids were well-tolerated at low to moderate
Conclusion: This MBMA provides clinically meaningful insights into the efficacy and safety profiles of oxycodone,
oxymorphone, and tramadol. Resultantly, the presented framework analysis can have an impact in the clinic on drug
development where it can guide: the optimization of doses of opioids required to manage osteoarthritic pain; the
making of precise key decisions for the positioning of new drugs, and; the design of more efficient trials.