Acetaminophen for osteoarthritis: Cochrane systematic review
Assessed as up to date: 2005/10/31
Osteoarthritis (OA) is the most common form of arthritis. Published guidelines and expert opinion are divided over the relative role of acetaminophen (also called paracetamol or Tylenol) and non-steroidal anti-inflammatory drugs (NSAIDs) as first-line pharmacologic therapy. The comparative safety of acetaminophen and NSAIDs is also important to consider. This update to the original 2003 review includes nine additional RCTs.Objectives
To assess the efficacy and safety of acetaminophen versus placebo and versus NSAIDs (ibuprofen, diclofenac, arthrotec, celecoxib, naproxen, rofecoxib) for treating OA.Search strategy
We searched MEDLINE (up to July 2005), EMBASE (2002-July 2005), Cochrane Central Register of Controlled Trials (CENTRAL), ACP Journal Club, DARE, Cochrane Database of Systematic Reviews (all from 1994 to July 2005). Reference lists of identified RCTs and pertinent review articles were also hand searched.Selection criteria
Published randomized controlled trials (RCTs) evaluating the efficacy and safety of acetaminophen alone in OA were considered for inclusion.Data collection and analysis
Pain, physical function and global assessment outcomes were reported. Results for continuous outcome measures were expressed as standardized mean differences (SMD). Dichotomous outcome measures were pooled using relative risk (RR) and the number needed to treat (NNT) was calculated.Main results
Fifteen RCTs involving 5986 participants were included in this review. Seven RCTs compared acetaminophen to placebo and ten RCTs compared acetaminophen to NSAIDs. In the placebo-controlled RCTs, acetaminophen was superior to placebo in five of the seven RCTs and had a similar safety profile. Compared to placebo, a pooled analysis of five trials of overall pain using multiple methods demonstrated a statistically significant reduction in pain (SMD -0.13, 95% CI -0.22 to -0.04), which is of questionable clinical significance. The relative percent improvement from baseline was 5% with an absolute change of 4 points on a 0 to 100 scale. The NNT to achieve an improvement in pain ranged from 4 to 16. In the comparator-controlled RCTs, acetaminophen was less effective overall than NSAIDs in terms of pain reduction, global assessments and in terms of improvements in functional status. No significant difference was found overall between the safety of acetaminophen and NSAIDs, although patients taking traditional NSAIDS were more likely to experience an adverse GI event (RR 1.47, (95% CI 1.08 to 2.00). 19% of patients in the traditional NSAID group versus 13% in the acetaminophen group experienced an adverse GI event. However, the median trial duration was only 6 weeks and it is difficult to assess adverse outcomes in a relatively short time period.Authors' conclusions
The evidence to date suggests that NSAIDs are superior to acetaminophen for improving knee and hip pain in people with OA. The size of the treatment effect was modest, and the median trial duration was only six weeks, therefore, additional considerations need to be factored in when making the decision between using acetaminophen or NSAIDs. In OA subjects with moderate-to-severe levels of pain, NSAIDs appear to be more effective than acetaminophen.
Towheed Tanveer, Maxwell Lara, Judd Maria, Catton Michelle, Hochberg Marc C, Wells George A
Acetaminophen for osteoarthritis
How well does acetaminophen work and compare to anti-inflammatories to treat osteoarthritis and is it safe?
Fifteen studies of moderate to high quality were reviewed and provide the best evidence we have today. The studies tested almost 6000 people with osteoarthritis of the hip or knee. The studies compared people who took 4000 mg of acetaminophen (Tylenol, Paracetamol) a day to people who took a placebo (fake pill) or non-steroidal anti-inflammatory drugs (NSAIDs). Most studies lasted on average about 6 weeks.
What is osteoarthritis and what drugs are used to treat it?
Osteoarthritis (OA) is the most common form of arthritis that can affect the hands, hips, shoulders and knees. In OA, the cartilage that protects the ends of the bones breaks down and causes pain and swelling. There are two main types of drug treatments in OA: acetaminophen which is used to relieve pain but does not affect swelling; and NSAIDs, such as ibuprofen, diclofenac and cox IIs (celecoxib), which are used to decrease pain and swelling. It is not clear which type is best to use or which causes more side effects: high doses of acetaminophen may cause stomach problems, such as ulcers, and NSAIDs may cause stomach, kidney or heart problems.
What did the studies show?
Acetaminophen compared to placebo
The studies show that people who took acetaminophen has less pain (when resting, moving, sleeping and overall) and felt better overall than people who took a placebo. Pain (when measured on a different scale), physical function and stiffness were about the same.
• Pain decreased by 4 more points on a scale of 0-100 for people who took acetaminophen instead of a placebo.
Implications for practice
Evidence available to date supports the efficacy of both acetaminophen and NSAIDs in the management of OA. There is also evidence that NSAIDs are superior to acetaminophen in terms of pain reduction and improvements in patient and physician global assessments and functional status. The relative superiority of NSAIDs over acetaminophen is most marked in those with moderate to severe levels of pain. The benefits of NSAIDs over acetaminophen are relatively modest, and therefore, additional factors are still important to consider in the decision to use these drugs. These factors include patient preferences, prescriber's clinical judgement, cost considerations and accessibility, and the comparative safety risks from both acetaminophen and NSAIDs in the individual patient.
Implications for research
Additional RCTs are necessary to help identify the patient with OA who is most likely to benefit from NSAIDs, as opposed to acetaminophen.
Moderate to severe levels of baseline OA pain may be associated with a better response to NSAIDs compared to acetaminophen; this requires further study. A strategy of combination NSAID and acetaminophen, depending on the severity of OA symptoms, may be more helpful than either drug alone, and this also needs to be studied systematically. Acetaminophen at doses greater than or equal to 2000 mg/day may also be associated with a significantly increased risk for upper GI complications and this unexpected finding requires confirmation from additional studies.
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