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. 2006 Jan 25;2006(1):CD004257.
doi: 10.1002/14651858.CD004257.pub2.

Acetaminophen for osteoarthritis

T E Towheed  1 , L Maxwell, M G Judd, M Catton, M C Hochberg, G Wells
Affiliations

Acetaminophen for osteoarthritis

T E Towheed et al. Cochrane Database Syst Rev. .

Abstract

Background: 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.

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Conflict of interest statement

None known.

Figures

1.1
1.1. Analysis
Comparison 1 Group 1: NSAID (ibuprofen 2400 mg, diclofenac, arthrotec, celecoxib, naproxen) vs Acetaminophen, Outcome 1 Rest Pain.
1.2
1.2. Analysis
Comparison 1 Group 1: NSAID (ibuprofen 2400 mg, diclofenac, arthrotec, celecoxib, naproxen) vs Acetaminophen, Outcome 2 HAQ Pain.
1.3
1.3. Analysis
Comparison 1 Group 1: NSAID (ibuprofen 2400 mg, diclofenac, arthrotec, celecoxib, naproxen) vs Acetaminophen, Outcome 3 Pain on motion (walking).
1.4
1.4. Analysis
Comparison 1 Group 1: NSAID (ibuprofen 2400 mg, diclofenac, arthrotec, celecoxib, naproxen) vs Acetaminophen, Outcome 4 HAQ Disability.
1.5
1.5. Analysis
Comparison 1 Group 1: NSAID (ibuprofen 2400 mg, diclofenac, arthrotec, celecoxib, naproxen) vs Acetaminophen, Outcome 5 50 Foot Walk Time.
1.6
1.6. Analysis
Comparison 1 Group 1: NSAID (ibuprofen 2400 mg, diclofenac, arthrotec, celecoxib, naproxen) vs Acetaminophen, Outcome 6 Physician Global (dichotomous).
1.7
1.7. Analysis
Comparison 1 Group 1: NSAID (ibuprofen 2400 mg, diclofenac, arthrotec, celecoxib, naproxen) vs Acetaminophen, Outcome 7 Physician Global (means).
1.8
1.8. Analysis
Comparison 1 Group 1: NSAID (ibuprofen 2400 mg, diclofenac, arthrotec, celecoxib, naproxen) vs Acetaminophen, Outcome 8 Patient Global (mean).
1.9
1.9. Analysis
Comparison 1 Group 1: NSAID (ibuprofen 2400 mg, diclofenac, arthrotec, celecoxib, naproxen) vs Acetaminophen, Outcome 9 Patient Global (dichotomous).
1.10
1.10. Analysis
Comparison 1 Group 1: NSAID (ibuprofen 2400 mg, diclofenac, arthrotec, celecoxib, naproxen) vs Acetaminophen, Outcome 10 Toxicity 1 (Total Number of Patients with any AE).
1.11
1.11. Analysis
Comparison 1 Group 1: NSAID (ibuprofen 2400 mg, diclofenac, arthrotec, celecoxib, naproxen) vs Acetaminophen, Outcome 11 Toxicity 2 (Withdrawals due to toxicity).
1.12
1.12. Analysis
Comparison 1 Group 1: NSAID (ibuprofen 2400 mg, diclofenac, arthrotec, celecoxib, naproxen) vs Acetaminophen, Outcome 12 WOMAC Pain.
1.13
1.13. Analysis
Comparison 1 Group 1: NSAID (ibuprofen 2400 mg, diclofenac, arthrotec, celecoxib, naproxen) vs Acetaminophen, Outcome 13 WOMAC Stiffness.
1.14
1.14. Analysis
Comparison 1 Group 1: NSAID (ibuprofen 2400 mg, diclofenac, arthrotec, celecoxib, naproxen) vs Acetaminophen, Outcome 14 WOMAC Function.
1.15
1.15. Analysis
Comparison 1 Group 1: NSAID (ibuprofen 2400 mg, diclofenac, arthrotec, celecoxib, naproxen) vs Acetaminophen, Outcome 15 WOMAC Total.
1.16
1.16. Analysis
Comparison 1 Group 1: NSAID (ibuprofen 2400 mg, diclofenac, arthrotec, celecoxib, naproxen) vs Acetaminophen, Outcome 16 Lequesne Pain.
1.17
1.17. Analysis
Comparison 1 Group 1: NSAID (ibuprofen 2400 mg, diclofenac, arthrotec, celecoxib, naproxen) vs Acetaminophen, Outcome 17 Lequesne Walking.
1.18
1.18. Analysis
Comparison 1 Group 1: NSAID (ibuprofen 2400 mg, diclofenac, arthrotec, celecoxib, naproxen) vs Acetaminophen, Outcome 18 Lequesne Function.
1.19
1.19. Analysis
Comparison 1 Group 1: NSAID (ibuprofen 2400 mg, diclofenac, arthrotec, celecoxib, naproxen) vs Acetaminophen, Outcome 19 Lequesne Total.
1.20
1.20. Analysis
Comparison 1 Group 1: NSAID (ibuprofen 2400 mg, diclofenac, arthrotec, celecoxib, naproxen) vs Acetaminophen, Outcome 20 Overall Pain (multiple methods).
2.1
2.1. Analysis
Comparison 2 Group 2: Acetaminophen vs Placebo, Outcome 1 Pain Response (dichotomous).
2.2
2.2. Analysis
Comparison 2 Group 2: Acetaminophen vs Placebo, Outcome 2 Pain on Motion (dichotomous).
2.3
2.3. Analysis
Comparison 2 Group 2: Acetaminophen vs Placebo, Outcome 3 Physician Global Assessment (dichotomous).
2.4
2.4. Analysis
Comparison 2 Group 2: Acetaminophen vs Placebo, Outcome 4 Patient Global Assessment (dichotomous).
2.5
2.5. Analysis
Comparison 2 Group 2: Acetaminophen vs Placebo, Outcome 5 Toxicity 1 (Total number of Patients with any AE).
2.6
2.6. Analysis
Comparison 2 Group 2: Acetaminophen vs Placebo, Outcome 6 WOMAC Pain.
2.7
2.7. Analysis
Comparison 2 Group 2: Acetaminophen vs Placebo, Outcome 7 WOMAC Stiffness.
2.8
2.8. Analysis
Comparison 2 Group 2: Acetaminophen vs Placebo, Outcome 8 WOMAC Function.
2.9
2.9. Analysis
Comparison 2 Group 2: Acetaminophen vs Placebo, Outcome 9 WOMAC Total.
2.10
2.10. Analysis
Comparison 2 Group 2: Acetaminophen vs Placebo, Outcome 10 Lequesne Pain.
2.11
2.11. Analysis
Comparison 2 Group 2: Acetaminophen vs Placebo, Outcome 11 Lequesne Walking.
2.12
2.12. Analysis
Comparison 2 Group 2: Acetaminophen vs Placebo, Outcome 12 Lequesne Function.
2.13
2.13. Analysis
Comparison 2 Group 2: Acetaminophen vs Placebo, Outcome 13 Lequesne Total.
2.14
2.14. Analysis
Comparison 2 Group 2: Acetaminophen vs Placebo, Outcome 14 Pain at rest.
2.15
2.15. Analysis
Comparison 2 Group 2: Acetaminophen vs Placebo, Outcome 15 Pain on passive motion.
2.16
2.16. Analysis
Comparison 2 Group 2: Acetaminophen vs Placebo, Outcome 16 Pain Response (continuous).
2.17
2.17. Analysis
Comparison 2 Group 2: Acetaminophen vs Placebo, Outcome 17 Stiffness at rest.
2.18
2.18. Analysis
Comparison 2 Group 2: Acetaminophen vs Placebo, Outcome 18 Day pain.
2.19
2.19. Analysis
Comparison 2 Group 2: Acetaminophen vs Placebo, Outcome 19 Night pain.
2.20
2.20. Analysis
Comparison 2 Group 2: Acetaminophen vs Placebo, Outcome 20 50 foot walk time.
2.21
2.21. Analysis
Comparison 2 Group 2: Acetaminophen vs Placebo, Outcome 21 MDHAQ VAS Pain.
2.22
2.22. Analysis
Comparison 2 Group 2: Acetaminophen vs Placebo, Outcome 22 Toxicity 2 (Withdrawals due to toxicity).
2.23
2.23. Analysis
Comparison 2 Group 2: Acetaminophen vs Placebo, Outcome 23 Overall Pain (multiple methods).
2.24
2.24. Analysis
Comparison 2 Group 2: Acetaminophen vs Placebo, Outcome 24 Patient Global Assessment (continuous).
3.1
3.1. Analysis
Comparison 3 Group 3: NSAIDS (ibuprofen 1200 mg,arthrotec, rofecoxib 25 mg, naproxen) vs Acetaminophen, Outcome 1 Rest pain.
3.2
3.2. Analysis
Comparison 3 Group 3: NSAIDS (ibuprofen 1200 mg,arthrotec, rofecoxib 25 mg, naproxen) vs Acetaminophen, Outcome 2 HAQ Pain.
3.3
3.3. Analysis
Comparison 3 Group 3: NSAIDS (ibuprofen 1200 mg,arthrotec, rofecoxib 25 mg, naproxen) vs Acetaminophen, Outcome 3 Pain on motion (walking).
3.4
3.4. Analysis
Comparison 3 Group 3: NSAIDS (ibuprofen 1200 mg,arthrotec, rofecoxib 25 mg, naproxen) vs Acetaminophen, Outcome 4 50 Foot Walk Time.
3.5
3.5. Analysis
Comparison 3 Group 3: NSAIDS (ibuprofen 1200 mg,arthrotec, rofecoxib 25 mg, naproxen) vs Acetaminophen, Outcome 5 HAQ disability index.
3.6
3.6. Analysis
Comparison 3 Group 3: NSAIDS (ibuprofen 1200 mg,arthrotec, rofecoxib 25 mg, naproxen) vs Acetaminophen, Outcome 6 Physician Global (Dichotomous).
3.7
3.7. Analysis
Comparison 3 Group 3: NSAIDS (ibuprofen 1200 mg,arthrotec, rofecoxib 25 mg, naproxen) vs Acetaminophen, Outcome 7 Patient Global (Dichotomous).
3.8
3.8. Analysis
Comparison 3 Group 3: NSAIDS (ibuprofen 1200 mg,arthrotec, rofecoxib 25 mg, naproxen) vs Acetaminophen, Outcome 8 Toxicity 1 (Total number of Patients with any AE).
3.9
3.9. Analysis
Comparison 3 Group 3: NSAIDS (ibuprofen 1200 mg,arthrotec, rofecoxib 25 mg, naproxen) vs Acetaminophen, Outcome 9 Toxicity 2 (Withdrawals due to toxicity).
3.10
3.10. Analysis
Comparison 3 Group 3: NSAIDS (ibuprofen 1200 mg,arthrotec, rofecoxib 25 mg, naproxen) vs Acetaminophen, Outcome 10 WOMAC Pain.
3.11
3.11. Analysis
Comparison 3 Group 3: NSAIDS (ibuprofen 1200 mg,arthrotec, rofecoxib 25 mg, naproxen) vs Acetaminophen, Outcome 11 WOMAC Stiffness.
3.12
3.12. Analysis
Comparison 3 Group 3: NSAIDS (ibuprofen 1200 mg,arthrotec, rofecoxib 25 mg, naproxen) vs Acetaminophen, Outcome 12 WOMAC Function.
3.13
3.13. Analysis
Comparison 3 Group 3: NSAIDS (ibuprofen 1200 mg,arthrotec, rofecoxib 25 mg, naproxen) vs Acetaminophen, Outcome 13 WOMAC Total.
3.14
3.14. Analysis
Comparison 3 Group 3: NSAIDS (ibuprofen 1200 mg,arthrotec, rofecoxib 25 mg, naproxen) vs Acetaminophen, Outcome 14 Overall Pain (multiple methods).
4.1
4.1. Analysis
Comparison 4 Group 4: NSAIDS (ibuprofen 1200 mg, arthrotec, rofecoxib 12.5 mg, naproxen) vs Acetaminophen, Outcome 1 Patient Global (Dichotomous).
4.2
4.2. Analysis
Comparison 4 Group 4: NSAIDS (ibuprofen 1200 mg, arthrotec, rofecoxib 12.5 mg, naproxen) vs Acetaminophen, Outcome 2 Toxicity 1 (Total Number of Patients with any AE).
4.3
4.3. Analysis
Comparison 4 Group 4: NSAIDS (ibuprofen 1200 mg, arthrotec, rofecoxib 12.5 mg, naproxen) vs Acetaminophen, Outcome 3 Toxicity 2‐ Withdrawals due to toxicity.
4.4
4.4. Analysis
Comparison 4 Group 4: NSAIDS (ibuprofen 1200 mg, arthrotec, rofecoxib 12.5 mg, naproxen) vs Acetaminophen, Outcome 4 WOMAC Pain.
4.5
4.5. Analysis
Comparison 4 Group 4: NSAIDS (ibuprofen 1200 mg, arthrotec, rofecoxib 12.5 mg, naproxen) vs Acetaminophen, Outcome 5 WOMAC Stiffness.
4.6
4.6. Analysis
Comparison 4 Group 4: NSAIDS (ibuprofen 1200 mg, arthrotec, rofecoxib 12.5 mg, naproxen) vs Acetaminophen, Outcome 6 WOMAC Function.
5.1
5.1. Analysis
Comparison 5 NSAIDs vs Acetaminophen ‐ GI outcomes, Outcome 1 Adverse events ‐ GI events.
5.2
5.2. Analysis
Comparison 5 NSAIDs vs Acetaminophen ‐ GI outcomes, Outcome 2 GI withdrawals.
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Update of

References

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