ATLANTA --New research presented at the 2019 ACR/ARP Annual Meeting suggests that opioids contribute no measurable benefit to quality of life or depression for patients with osteoarthritis (OA). Researchers also found only small benefits on pain and function after two to 12 weeks of treatment, and interestingly, strong opioids had consistently worse pain relief benefits and a greater risk of any safety-related outcome than weak opioids in this meta-analysis. (Abstract #910).
Osteoarthritis is a common joint disease that most often affects middle-age to elderly people. OA is a disease of the entire joint, involving the cartilage, joint lining, ligaments and bone. OA is characterized by breakdown of cartilage tissue, bony changes of the joints, deterioration of tendons and ligaments, and various degrees of inflammation of the joint lining (called the synovium).
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. 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," says 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.
The study included meta-analyses of pain and function at two, four, eight, and 12 weeks. It also analyzed relevant safety outcomes for all opioids, as well as strong versus weak opioids. They searched MEDLINE and the Cochrane Database from inception to April 2019, and actively sought unpublished data.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
Of the 23 randomized controlled trials included, there were 11,402 participants and 64 percent were female. The participants' mean age ranged from 54 to 67 years. Their mean body-mass index (BMI) ranged from 28 to 34 kg/m2. All of the trials included in the study were of moderate quality, and potential attrition bias was the primary methodological 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 two, four, eight, and 12 weeks. Opioids had no impact on quality of life or depression.
Strong opioids consistently had smaller benefits on pain than weak opioids, the study found. Though 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 possible reason is 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," says Dr. Bannuru. "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."
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ABSTRACT
Is There Any Role for Opioids in the Management of OA?
Background/Purpose: Opioids have long been prescribed for chronic pain conditions, including osteoarthritis (OA). Although the safety of opioids has been questioned, there is little information about their temporal efficacy. Additionally, differences in overall efficacy and safety between strong versus weak opioid classes have not been clearly delineated. We conducted meta-analyses of pain and function at 2, 4, 8, and 12 weeks and analyzed relevant safety outcomes for all opioids, as well as strong versus weak opioids.
Methods: We searched MEDLINE and the Cochrane Database from inception to April 2019 and actively sought unpublished data. Placebo-controlled RCTs assessing the efficacy and/or safety of FDA-approved opioids in patients with knee and/or hip OA were included. We excluded studies using enriched enrollment or double-dummy design involving non-oral treatments. Screening and data extraction were undertaken by two reviewers. We calculated standardized mean differences and risk ratios with 95% confidence intervals. Study quality was assessed using Cochrane risk of bias tool. Random effects meta-analyses were performed, and heterogeneity assessed using the I2 statistic. Subgroup analyses of strong and weak opioids were conducted for pain at every time point, and for safety outcomes. Meta-regression was performed to assess the impact of dosage (morphine equivalency) on pain relief.
Results: The included 23 RCTs comprised 11,402 participants. 64% were female. The mean age ranged from 54 to 67 years; mean BMI from 28 to 34 kg/m2. All trials were of moderate quality with potential attrition bias being the primary methodological concern. Overall, opioids demonstrated small, statistically significant benefits on pain at each time point ranging from -0.28 to -0.19 (Figure 1); similarly, small, statistically significant effects were observed with respect to function at 2, 4, and 12 weeks ranging from -0.26 to -0.16. Opioids had no impact on quality of life or depression; participants who received opioids reported significantly higher quality of sleep. We found that strong opioids had consistently smaller benefits on pain than weak opioids (Figure 1). Meta-regression revealed that opioid dosage (morphine equivalency) has no impact on pain relief (p=0.09) (Figure 2). Methodological bias (selection, attrition) may contribute to the poor performance of strong opioids, or perhaps a pharmacodynamic classification of "strong" has been incorrectly equated with the clinical efficacy of these drugs. Strong opioids showed a safety profile consistently worse than weak opioids, particularly with respect to drug withdrawal symptoms (2.78 [1.41, 5.49] versus 1.06 [0.19, 5.80]) and discontinuations due to adverse events (5.47 [4.63, 6.47] versus 2.77 [2.26, 3.39]).
Conclusions: Overall, opioids demonstrate only small benefits on pain and function from 2 to 12 weeks of treatment and contribute no measurable benefit to QOL or depression versus placebo. Strong opioids demonstrated consistently worse pain relief, with greater risk of any safety outcome than weak opioids. In light of this evidence, clinicians and policy makers should reconsider the utility of strong opioids in the management of OA.