Therapeutics

Review: In knee or hip OA, opioids reduce pain and improve function but increase adverse events Clinical impact ratings:

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da Costa BR, Nu¨esch E, Kasteler R, et al. Oral or transdermal opioids for osteoarthritis of the knee or hip. Cochrane Database Syst Rev. 2014;9:CD003115.

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Question

Conclusion

In patients with knee or hip osteoarthritis (OA), what are the efficacy and safety of opioids?

In patients with knee or hip osteoarthritis, opioids reduce pain and improve function but increase adverse events.

Review scope

Sources of funding: Swiss National Science Foundation and Marie Curie Intra-European Fellowship.

Included studies compared oral or transdermal opioids (excluding tramadol) with placebo or no intervention in patients with OA of the knee or hip confirmed by clinical or radiologic criteria. Outcomes were pain, function, adverse events, serious adverse events (hospital admission, prolongation of hospital stay, persistent or significant disability, congenital abnormality or birth defect in offspring, life-threatening events, or death), withdrawal due to adverse events, and symptoms of opioid dependence (craving or physical withdrawal symptoms).

For correspondence: Dr. B.R. da Costa, University of Bern, Bern, Switzerland. E-mail [email protected]. 

Commentary Pain is the key symptom that affects quality of life in people living with OA of the hip or knee. The well-conducted systematic review by da Costa and colleagues found that opioids improve pain and function compared with placebo. Although the results may seem encouraging, the median duration of trials assessing pain was only 4 weeks; however, OA is a chronic disease with fluctuations in pain over many years. Given the increase in adverse events found in these short-term studies, opioids should not be used for routine long-term treatment.

Review methods MEDLINE, EMBASE/Excerpta Medica, and Cochrane Central Register of Controlled Trials (all to Aug 2012); CINAHL (to Jul 2008); conference proceedings, reference lists, Science Citation Index, and clinical trial registries were searched for randomized controlled trials (RCTs) and quasi-RCTs; experts were contacted. 22 RCTs (n = 8275, mean age 53 to 66 y, median treatment duration 4 wk) met selection criteria. 8 RCTs described adequate randomization and allocation concealment; blinding was explicit for patients and outcome assessors in 15 RCTs and for physicians in 14. Weak opioids (oral codeine) were assessed in 3 RCTs and strong opioids in 19 (oral hydromorphone and transdermal fentanyl in 1, oral morphine and oral oxymorphone in 2, oral tapentadol and transdermal buprenorphine in 4, and oral oxycodone in 10). Seventeen RCTs included only patients who had insufficient response to paracetamol, nonsteroidal antiinflammatory drugs, or previous opioid treatments. The comparator was placebo in 20 RCTs and no intervention in 2.

Patients in 17 trials had insufficient response to paracetamol and nonsteroidal agents. The review did not report whether such interventions as exercise and weight loss had been used, and no head-to-head comparisons of opioids with other effective treatment regimens were done. Too often, patients are on waiting lists for joint replacement surgery but have not been offered, or supported in using, maximal nonpharmacologic and conservative approaches. Together, clinicians and patients need to determine whether the small to moderate improvements in pain and function with opioids are worthwhile given the risk for adverse effects and the unknown effects of prolonged use. Opioids may be considered as a last resort in patients in whom maximal conservative therapy has failed and who are not candidates for surgery. Documentation of longer-term benefits and harms of opioids should be undertaken.

Main results Opioids reduced pain and improved function but increased adverse events, withdrawal due to adverse events, and symptoms of opioid dependency (Table).

Lyn March, MD Institute of Bone and Joint Research University of Sydney and Royal North Shore Hospital St Leonards, New South Wales, Australia

Opioids vs placebo or no intervention in patients with hip or knee osteoarthritis* Outcomes

Number of trials (n)

Median follow-up (wk)

SMD (95% CI)†

NNT (CI)

I2

Pain

22 (8275)

4

⫺0.28 (⫺0.35 to ⫺0.20) 10 (8 to 14)

58%

Function

12 (3553)

5

⫺0.26 (⫺0.35 to ⫺0.17) 11 (7 to 14)

32%

RRI (CI) Any adverse event Any serious adverse event Withdrawal due to adverse event Opioid dependency

49% (35 to 63)

NNH (CI)

10 (4898)

8

3 (681)

8

235% (⫺17 to 1256)

Not significant

14 (11 to 19)

71% 0%

21 (8128)

6

276% (193 to 382)

21 (15 to 30)

59%

3 (not reported)

16

176% (102 to 277)

65 (42 to 110)

0%

*SMD = standard mean difference; other abbreviations defined in Glossary. RRI and CI calculated from risk ratios in article using a random-effects model. †SMD of ⫺0.20 standard deviation units is considered a small difference between groups.

姝 2015 American College of Physicians JC8 ACP Journal Club Downloaded From: http://annals.org/ by a Penn State University Hershey User on 05/27/2015

Annals of Internal Medicine

17 February 2015

ACP Journal Club: review: in knee and hip OA, opioids reduce pain and improve function but increase adverse events.

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