Bannuru reports no relevant financial disclosures. Co-author , of Lund University, in Sweden, reports personal fees from Arthro Therapeutics AB, GlaxoSmithKline, Janssen, Pfizer and Regeneron.
Opioids offer only minimal relief of osteoarthritis symptoms within a 12-week period, and cause discomfort in most patients, according to findings published in Arthritis Care & Research.
“We wanted to assess the impact of opioids on all patient-centered outcomes to produce results that would be relevant to patients and clinicians alike,” Raveendhara R. Bannuru, MD, PhD, FAGE, of Tufts University Medical Center in Boston told Healio Rheumatology. “Though the risks of opioid use are relatively well known, some patients and providers still favor using the drugs. We hoped to explore some understudied outcomes that could hold clues as to what benefits, if any, opioids offer to patients.
“Our study is unique because we estimated the trajectory of the impact that opioids have on pain and functional outcomes in OA patients over time,” he added. “Temporal assessments can illustrate an optimal therapeutic window within which a treatment is most efficacious.”
To examine temporal patterns in pain relief and functional improvement in patients treated with opioids for knee or hip OA, and assess their safety, Bannuru and colleagues conducted a systematic review and meta-analysis of randomized controlled trials. They searched Medline, Embase, PubMed Central and the Cochrane Central Register of Controlled Trials from inception to December. The researchers also sought out unpublished data. In all, Bannuru and colleagues included 18 placebocontrolled trials of oral opioids, covering 9,283 patients with knee or hip OA.
The researchers calculated standardized mean differences for pain and function at 2, 4, 8 and 12 weeks, and conducted subgroup analyses for strong and weak/intermediate opioids. Additionally, they performed metaregression to analyze the impact of dosage on pain relief, based on morphine equivalency. Lastly, Bannuru and colleagues calculated risk ratios for safety at the final followup.
According to the researchers, opioids provided small benefits regarding pain at each time point, with standardized mean differences ranging from –0.28 (95% CI, –0.38 to –0.17) to –0.19 (95% CI, –0.29 to –0.08), with similar effects regarding function. In addition, strong opioids demonstrated consistently inferior efficacy and overall worse safety compared with weak or intermediate opioids. A metaregression analysis suggested that incremental pain relief achieved beyond 20 to 50 mg doses was not substantial in light of increased safety risks, the researchers wrote.
“Our results suggest that oral opioids have only small benefits on pain and function in OA,” Bannuru said. “Additionally, we found that the magnitude of these effects remains small and continues to decrease over time. We also found that strong opioids consistently underperformed compared to weak or intermediate opioids.
“On the other hand, participants who received opioids were significantly more likely to experience adverse events, especially gastrointestinal discomfort and daytime drowsiness,” he added. “In light of dependency concerns and the discomfort that many patients feel while taking the drugs, it would appear that there is no optimal therapeutic window for the use of oral opioids in OA.”