Opioids Offer Only Minor Pain Relief and Function Benefits for Patients with OA

Opioids contribute no measurable benefit to quality of life or depression for patients with osteoarthritis (OA), although they provide a small benefit in pain and function after 2 to 12 weeks of treatment, according to new research presented at the 2019 ACR/ARP Annual Meeting.

Interestingly, strong opioids were associated with consistently worse pain relief benefits and a greater risk of any safety-related outcome than weak opioids in this meta-analysis.

Opioids, long prescribed for chronic pain, have many safety concerns. The lack of information about opioids’ efficacy for OA pain relief, and no clear delineation between overall efficacy and safety between strong and weak opioids, prompted the study.

“Given the current controversy regarding the use of opioids in chronic pain, we wanted to delve deeper into the efficacy and safety profiles of oral opioid drugs in osteoarthritis patients. Temporal assessments can reveal peak periods of efficacy and can provide clinicians with a blueprint for optimal durations of treatment regimens,” said Raveendhara R. Bannuru MD, PhD, FAGE, director of the Center for Treatment Comparison and Integrative Analysis at Tufts Medical Center in Boston and the study’s lead author.

“Our study also provides an important update to the evidence body by evaluating patient reported outcomes of quality of life, depression and sleep that are relevant to clinicians and patients alike.”

The study included meta-analyses of pain and function at 2, 4, 8, and 12 weeks. It also analyzed relevant safety outcomes for all opioids, as well as strong versus weak opioids. The researchers searched MEDLINE and the Cochrane Database from inception to April 2019, and actively sought unpublished data. They included placebo-controlled, randomized controlled trials assessing the efficacy and/or safety of FDA-approved opioids in patients with knee and/or hip OA

The 23 randomized controlled trials in the analysis included 11,402 participants, 64% of whom were female. The participants’ ranged in age from 54 to 67 years, with a body mass index (BMI) ranging from 28 to 34. All trials included in the study were of moderate quality, and potential attrition bias was the primary methodologic concern.

Overall, the results showed that opioids demonstrated small, statistically significant benefits on pain at each time point. Similarly, the researchers observed small, statistically significant effects on function at 2, 4, 8, and 12 weeks. Opioids had no impact on quality of life or depression.

Strong opioids consistently conferred smaller benefits on pain than weak opioids, the study authors found. Although results of meta-regression exploring dose effects revealed a relevant relationship between opioid dosage, or morphine equivalency, and the magnitude of pain relief, participants receiving strong opioids were nearly twice as likely to discontinue due to adverse events than those receiving weak/intermediate opioids.

One reason may have been that many participants who received strong opioids were unable to achieve the optimal therapeutic dose as a result of attrition related to a lack of tolerability. Strong opioids overall showed a consistently worse safety profile than weak opioids, particularly drug withdrawal symptoms and discontinuations due to adverse events.

“Strong opioids’ underperformance was the study’s most interesting finding, and likely due to the relationship between pain relief and tolerability of opioids based on dose,” Dr. Bannuru said. “We observed a relevant relationship between morphine dose equivalency and the magnitude of pain relief at the final follow-up.

“However, the relative risk of discontinuation due to adverse events among participants receiving strong opioids was nearly twice that of participants receiving weak opioids. These results suggest that many people who receive strong opioids may be unable to achieve the optimal therapeutic dose due to a lack of tolerability.”


Osani M, Lohmander S, Bannuru R. Is There Any Role for Opioids in the Management of OA? (Abstract 910). Presented at the 2019 ACR/ARP Annual Meeting, November 8-13, Atlanta, Georgia.

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