Oral or transdermal opioids for osteoarthritis of the knee or hip

BACKGROUND: Osteoarthritis is the most common form of joint disease and theleading cause of pain and physical disability in older people. Opioids may be aviable treatment option if people have severe pain or if other analgesics arecontraindicated. However, the evidence about their effectiveness and safety iscontradictory. This is an update of a Cochrane review first published in 2009.OBJECTIVES: To determine the effects on pain, function, safety, and addiction of oral or transdermal opioids compared with placebo or no intervention in peoplewith knee or hip osteoarthritis.SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials(CENTRAL), MEDLINE, EMBASE and CINAHL (up to 28 July 2008, with an updateperformed on 15 August 2012), checked conference proceedings, reference lists,and contacted authors.SELECTION CRITERIA: We included randomised or quasi-randomised controlled trials that compared oral or transdermal opioids with placebo or no treatment in people with knee or hip osteoarthritis. We excluded studies of tramadol. We applied nolanguage restrictions.DATA COLLECTION AND ANALYSIS: We extracted data in duplicate. We calculatedstandardised mean differences (SMDs) and 95% confidence intervals (CI) for painand function, and risk ratios for safety outcomes. We combined trials using aninverse-variance random-effects meta-analysis.MAIN RESULTS: We identified 12 additional trials and included 22 trials with 8275participants in this update. Oral oxycodone was studied in 10 trials, transdermalbuprenorphine and oral tapentadol in four, oral codeine in three, oral morphineand oral oxymorphone in two, and transdermal fentanyl and oral hydromorphone inone trial each. All trials were described as double-blind, but the risk of biasfor other domains was unclear in several trials due to incomplete reporting.Opioids were more beneficial in pain reduction than control interventions (SMD-0.28, 95% CI -0.35 to -0.20), which corresponds to a difference in pain scoresof 0.7 cm on a 10-cm visual analogue scale (VAS) between opioids and placebo.This corresponds to a difference in improvement of 12% (95% CI 9% to 15%) betweenopioids (41% mean improvement from baseline) and placebo (29% mean improvementfrom baseline), which translates into a number needed to treat (NNTB) to causeone additional treatment response on pain of 10 (95% CI 8 to 14). Improvement of function was larger in opioid-treated participants compared with control groups(SMD -0.26, 95% CI -0.35 to -0.17), which corresponds to a difference in functionscores of 0.6 units between opioids and placebo on a standardised Western Ontarioand McMaster Universities Arthritis Index (WOMAC) disability scale ranging from 0to 10. This corresponds to a difference in improvement of 11% (95% CI 7% to 14%) between opioids (32% mean improvement from baseline) and placebo (21% meanimprovement from baseline), which translates into an NNTB to cause one additionaltreatment response on function of 11 (95% CI 7 to 14). We did not findsubstantial differences in effects according to type of opioid, analgesicpotency, route of administration, daily dose, methodological quality of trials,and type of funding. Trials with treatment durations of four weeks or less showedlarger pain relief than trials with longer treatment duration (P value forinteraction = 0.001) and there was evidence for funnel plot asymmetry (P value = 0.054 for pain and P value = 0.011 for function). Adverse events were morefrequent in participants receiving opioids compared with control. The pooled riskratio was 1.49 (95% CI 1.35 to 1.63) for any adverse event (9 trials; 22% ofparticipants in opioid and 15% of participants in control treatment experiencedside effects), 3.76 (95% CI 2.93 to 4.82) for drop-outs due to adverse events (19trials; 6.4% of participants in opioid and 1.7% of participants in controltreatment dropped out due to adverse events), and 3.35 (95% CI 0.83 to 13.56) forserious adverse events (2 trials; 1.3% of participants in opioid and 0.4% ofparticipants in control treatment experienced serious adverse events). Withdrawalsymptoms occurred more often in opioid compared with control treatment (oddsratio (OR) 2.76, 95% CI 2.02 to 3.77; 3 trials; 2.4% of participants in opioidand 0.9% of participants control treatment experienced withdrawal symptoms).AUTHORS' CONCLUSIONS: The small mean benefit of non-tramadol opioids arecontrasted by significant increases in the risk of adverse events. For the painoutcome in particular, observed effects were of questionable clinical relevancesince the 95% CI did not include the minimal clinically important difference of0.37 SMDs, which corresponds to 0.9 cm on a 10-cm VAS.