The effectiveness and safety of nonsteroidal anti-inflammatory drugs (NSAIDs) and opioids for the management of knee and hip osteoarthritis (OA) pain were determined in a meta-analysis published in BMJ.

Systematic reviews presenting evidence on the effectiveness and safety of NSAIDs and opioids to treat OA pain are lacking in that these analyses used clustered drug doses or classes, which do not provide sufficient granular data.

In the current systemic review and network meta-analysis, the study authors sought to assess the effectiveness and safety of different preparations and doses of NSAIDs, opioids, and acetaminophen for knee and hip OA pain and physical function.

Continue Reading

They compared 90 different active preparations or doses of NSAIDs (68), opioids (19), and acetaminophen (3) from 181 publications describing 192 trials (n=102,829).

Results showed that 74.5% of oral NSAID, 33.3% of topical NSAID, 22.2% of opioid, and 33.3% of acetaminophen interventions had statistical superiority compared with oral placebo. Seven NSAIDs showed a 95% probability of pronounced treatment effects than the minimal clinically relevant reduction in pain, of which, 5 oral preparations (diclofenac, 150 mg/d, etoricoxib, 60 and 90 mg/d, and rofecoxib, 25 and 50 mg/d) had at least 99% probability.

Topical diclofenac (70-81 mg/d and 140-160 mg/d) had a 92.3% or greater probability of a pronounced treatment effect than the minimal clinically relevant reduction in pain, irrespective of dose.

All opioids had a 53% or lower probability of exceeding the minimal clinically relevant reduction in pain.

In the safety analysis, oral NSAIDs and opioid interventions had 29.8% and 89.5% increased risk for any adverse event, respectively. Opioid and oral NSAID interventions were associated with 83.3% and 18.5% increased risk for dropouts due to adverse events, respectively. Topical NSAIDs had no risk for adverse events and dropouts. The opioid oxymorphone, at 80 mg/day, had the highest risk for adverse events (88%) and dropouts (51%) due to adverse events.

Study limitations included approximate representation of outcome data within a trial and the improper representation of linear trends in the random walk model.

Authors of the analysis concluded, “Physicians could use the results of our analysis to identify the lowest doses of different drug preparations that are effective and safe when first prescribing treatment, as generally recommended by current clinical practice guidelines.”

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


da Costa BR, Pereira TV, Saadat P, et al. Effectiveness and safety of non-steroidal anti-inflammatory drugs and opioid treatment for knee and hip osteoarthritis: network meta-analysis. BMJ. 2021;375:n2321. Published October 12, 2021. doi:10.1136/bmj.n2321