Oral or transdermal opioids for osteoarthritis of the knee or hip

BACKGROUND: Osteoarthritis is the most common form of joint disease and the
leading cause of pain and physical disability in older people. Opioids may be a
viable treatment option if people have severe pain or if other analgesics are
contraindicated. However, the evidence about their effectiveness and safety is
contradictory. 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 people
with 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 update
performed 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 no
language restrictions.
DATA COLLECTION AND ANALYSIS: We extracted data in duplicate. We calculated
standardised mean differences (SMDs) and 95% confidence intervals (CI) for pain
and function, and risk ratios for safety outcomes. We combined trials using an
inverse-variance random-effects meta-analysis.
MAIN RESULTS: We identified 12 additional trials and included 22 trials with 8275
participants in this update. Oral oxycodone was studied in 10 trials, transdermal
buprenorphine and oral tapentadol in four, oral codeine in three, oral morphine
and oral oxymorphone in two, and transdermal fentanyl and oral hydromorphone in
one trial each. All trials were described as double-blind, but the risk of bias
for 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 scores
of 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%) between
opioids (41% mean improvement from baseline) and placebo (29% mean improvement
from baseline), which translates into a number needed to treat (NNTB) to cause
one 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 function
scores of 0.6 units between opioids and placebo on a standardised Western Ontario
and McMaster Universities Arthritis Index (WOMAC) disability scale ranging from 0
to 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% mean
improvement from baseline), which translates into an NNTB to cause one additional
treatment response on function of 11 (95% CI 7 to 14). We did not find
substantial differences in effects according to type of opioid, analgesic
potency, route of administration, daily dose, methodological quality of trials,
and type of funding. Trials with treatment durations of four weeks or less showed
larger pain relief than trials with longer treatment duration (P value for
interaction = 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 more
frequent in participants receiving opioids compared with control. The pooled risk
ratio was 1.49 (95% CI 1.35 to 1.63) for any adverse event (9 trials; 22% of
participants in opioid and 15% of participants in control