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Review
. 2016 Jun;24(6):962-72.
doi: 10.1016/j.joca.2016.01.135. Epub 2016 Feb 1.

Comparative pain reduction of oral non-steroidal anti-inflammatory drugs and opioids for knee osteoarthritis: systematic analytic review

S R Smith  1 , B R Deshpande  2 , J E Collins  3 , J N Katz  4 , E Losina  5
Affiliations
Review

Comparative pain reduction of oral non-steroidal anti-inflammatory drugs and opioids for knee osteoarthritis: systematic analytic review

S R Smith et al. Osteoarthritis Cartilage. 2016 Jun.

Abstract

Objective: Summarize the comparative effectiveness of oral non-steroidal anti-inflammatory drugs (NSAIDs) and opioids in reducing knee osteoarthritis (OA) pain.

Methods: Two reviewers independently screened reports of randomized controlled trials (RCTs), published in English between 1982 and 2015, evaluating oral NSAIDs or opioids for knee OA. Included studies were at least 8 weeks duration, conducted in Western Europe, the Americas, New Zealand, or Australia, and reported baseline and follow-up pain using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain subscale (0-100, 100-worst). Effectiveness was evaluated as reduction in pain, accounting for study dropout and heterogeneity.

Results: Twenty-seven treatment arms (nine celecoxib, four non-selective NSAIDs [diclofenac, naproxen, piroxicam], eleven less potent opioids [tramadol], and three potent opioids [hydromorphone, oxycodone]) from 17 studies were included. NSAID and opioid studies reported similar baseline demographics and efficacy withdrawal rates; NSAID studies reported lower baseline pain and toxicity withdrawal rates. Accounting for efficacy-related withdrawals, all drug classes were associated with similar pain reductions (NSAIDs: -18; less potent opioids: -18; potent opioids: -19). Meta-regression did not reveal differential effectiveness by drug class but found that study cohorts with a higher proportion of male subjects and worse mean baseline pain had greater pain reduction. Similarly, results of the network meta-analysis did not find a significant difference in WOMAC Pain reduction for the three analgesic classes.

Conclusion: NSAIDs and opioids offer similar pain relief in OA patients. These data could help clinicians and patients discuss likely benefits of alternative analgesics.

Keywords: Knee osteoarthritis; Meta-analysis; NSAIDs; Network meta-analysis; Opioids; WOMAC Pain subscale.

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Conflict of interest statement

Dr. Katz is the President-Elect of the Osteoarthritis Research Society International. Drs. Katz and Losina are Deputy Editors for Biostatistics and Methodology for the Journal of Bone and Joint Surgery. All other authors have no conflicts of interest to report.

Figures

Figure 1
Figure 1
One study included both NSAIDs and opioids treatment groups and is represented in both arms in this figure. Abbreviations: OA, osteoarthritis; NSAID, non-steroidal anti-inflammatory drug; WOMAC Pain, Western Ontario and McMaster Universities Osteoarthritis Index Pain Subscale
Figure 2
Figure 2
This figure displays the funnel plot of precision (reciprocal of the variance) by mean change from baseline, modified for efficacy-related withdrawals, in WOMAC Pain for all included studies of (a) NSAIDs and (b) opioids. The NSAIDs funnel plot appears fairly symmetrical, and Egger’s test was not statistically significant (p=0.50). The opioids funnel plot is asymmetrical, with more studies reporting more change and fewer studies with lower precision reporting less change; Egger’s test was borderline statistically significant (p=0.05). The dashed lines represent combined efficacy estimates from a random effects model of the two classes of analgesics (NSAIDs: −18; opioids: −19).
Figure 2
Figure 2
This figure displays the funnel plot of precision (reciprocal of the variance) by mean change from baseline, modified for efficacy-related withdrawals, in WOMAC Pain for all included studies of (a) NSAIDs and (b) opioids. The NSAIDs funnel plot appears fairly symmetrical, and Egger’s test was not statistically significant (p=0.50). The opioids funnel plot is asymmetrical, with more studies reporting more change and fewer studies with lower precision reporting less change; Egger’s test was borderline statistically significant (p=0.05). The dashed lines represent combined efficacy estimates from a random effects model of the two classes of analgesics (NSAIDs: −18; opioids: −19).
Figure 3
Figure 3
This figure portrays the mean change from baseline, modified for efficacy-related withdrawals, in WOMAC Pain (with 95% confidence intervals [CIs]) for all included studies of (a) NSAIDs, (b) less potent opioids, and (c) potent opioids.
Figure 3
Figure 3
This figure portrays the mean change from baseline, modified for efficacy-related withdrawals, in WOMAC Pain (with 95% confidence intervals [CIs]) for all included studies of (a) NSAIDs, (b) less potent opioids, and (c) potent opioids.
Figure 3
Figure 3
This figure portrays the mean change from baseline, modified for efficacy-related withdrawals, in WOMAC Pain (with 95% confidence intervals [CIs]) for all included studies of (a) NSAIDs, (b) less potent opioids, and (c) potent opioids.
Figure 4
Figure 4
The trim and fill method was utilized to impute hypothetical missing publications (indicated with a dash) for less potent opioids, as the funnel plot initially exhibited significant asymmetry. Though the peak remains uncentered, the plot is more symmetric, and Egger’s test is no longer statistically significant (p=0.57).
Figure 5
Figure 5
This figure depicts the direct and indirect comparisons between NSAIDs, less potent opioids, potent opioids, and placebo treatment arms among included studies. Abbreviations: NSAIDs, non-steroidal anti-inflammatory drugs.
See this image and copyright information in PMC

References

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