Therapeutics
Review: Acetaminophen reduces pain in hip or knee osteoarthritis by a small amount, but not low back pain Clinical impact ratings:
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Machado GC, Maher CG, Ferreira PH, et al. Efficacy and safety of paracetamol for spinal pain and osteoarthritis: systematic review and meta-analysis of randomised placebo controlled trials. BMJ. 2015;350:h1225.
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Question
Source of funding: No external funding.
What are the efficacy and safety of acetaminophen (paracetamol) for spinal pain and osteoarthritis (OA) of the hip or knee?
For correspondence: G. C. Machado, The George Institute for Global Health, University of Sydney, Sydney, New South Wales, Australia. E-mail [email protected].
Review scope Included studies compared acetaminophen with placebo in patients with nonspecific spinal pain (neck or low back pain) or OA of the hip or knee. Exclusion criteria were serious pathologic spinal conditions; mixed arthritis populations if data for separate indications were not reported; or immediate analgesia after spinal, hip, or knee surgery. Outcomes included pain, disability, quality of life, adverse events, and abnormal liver enzyme levels (≥ 1.5 times the upper limit of the reference range).
Review methods MEDLINE, EMBASE/Excerpta Medica, AMED, CINAHL, Web of Science, LILACS, International Pharmaceutical Abstracts, and Cochrane Central Register of Controlled Trials (all to Dec 2014), reference lists, relevant Web sites, and clinical trial registries were searched for randomized controlled trials (RCTs). 13 RCTs (n = 5366, mean age range 35 to 70 y) met selection criteria: 10 in patients with OA (n = 3541) and 3 in patients with low back pain (n = 1825). One RCT used IV acetaminophen for chronic low back pain. Acetaminophen dose ranged from 3900 to 4000 mg/d in 10 RCTs and was 3000 mg/d in 3 RCTs. Risk for bias was low for randomization in 4 RCTs; for allocation in 3 RCTs; and for blinding of patients, personnel, and outcome assessors in 12 RCTs. 8 RCTs had immediate outcome assessment (≤ 2 wk), and 9 RCTs had short-term assessment (> 2 wk but ≤ 3 mo); 1 RCT with assessment at 6 months was pooled with short-term RCTs.
Main results The main results are in the Table. Groups did not differ for adverse events, but acetaminophen increased risk for abnormal liver enzyme tests (3 RCTs, n = 1237, relative risk increase 280%, 95% CI 90 to 640).
Conclusion Acetaminophen reduces pain and disability by a small amount in the short term in patients with hip or knee osteoarthritis but not in patients with low back pain.
Commentary Clinical practice guidelines recommend acetaminophen as a first-line medication for spinal pain and OA (1, 2), but the metaanalysis by Machado and colleagues found that the benefits of acetaminophen on short-term pain and disability in patients with OA were below thresholds for clinically important differences. For spinal pain, acetaminophen had essentially no effect. Although evidence on long-term outcomes is lacking, effects would probably not be larger than short-term effects. Acetaminophen did not increase risk for clinical adverse events but increased risk for elevated liver enzymes. Although the systematic review was well done, the evidence base for spinal pain is quite limited: 1 of the 2 trials was small (n = 72), measured only immediate pain relief, and has since been retracted by the authors (3). In addition, the trial evaluated single-dose IV acetaminophen in patients receiving long-term opioids, limiting its generalizability. Initial studies often report results that are subsequently overturned (4), making the findings less than conclusive. For OA, results were based on 3 to 7 trials and were generally consistent, increasing certainty in the findings. The review by Machado and colleagues raises important questions about the role of acetaminophen. For acute spinal pain, future trials should measure analgesia several hours after dosing, which may be the most relevant outcome for patients seeking immediate relief. For OA, head-to-head trials have shown that nonsteroidal antiinflammatory drugs (NSAIDs) are only slightly better than acetaminophen (5). Given its favorable side effect profile and low cost and the potential harms of such alternatives as opioids and NSAIDs, abandoning acetaminophen seems premature, particularly for older adults for whom safe and effective options are limited. However, clinicians prescribing acetaminophen should recognize that benefits are probably small at best. Roger Chou, MD Oregon Health & Science University Portland, Oregon, USA
Acetaminophen vs placebo for low back pain and osteoarthritis of the hip or knee* Outcomes†
Pain
Disability
Indication
Time of assessment‡
Low back pain
Immediate Short-term
1 (1526)
⫺0.5 (⫺2.9 to 1.9)
Osteoarthritis
Immediate
5 (1686)
⫺3.3 (⫺5.8 to ⫺0.8)
Short-term||
7 (2355)
⫺3.7 (⫺5.5 to ⫺1.9)
Immediate
1 (1511)
⫺1.9 (⫺4.8 to 1.0)
Short-term
1 (1522)
0.4 (⫺1.7 to 2.5)
Immediate
3 (1336)
⫺1.7 (⫺6.0 to 2.6)
Short-term||
7 (2354)
⫺2.9 (⫺4.9 to ⫺0.9)
Low back pain
Osteoarthritis
Number of trials (n) 2 (1592)
Weighted mean difference (95% CI)§ 1.4 (⫺1.3 to 4.1)
*Abbreviations defined in Glossary. †Scores for pain and disability were converted to a common scale ranging from 0 (no pain or disability) to 100 (worse pain or disability). ‡Immediate assessment (≤ 2 wk); short-term assessment (> 2 wk but ≤ 3 mo). §Weighted mean difference using a random-effects model. Negative value = improvement with acetaminophen. Minimal clinically important difference = 9 on a 0 to 100 scale. ||Includes 1 trial with assessment at 6 mo (n = 212).
姝 2015 American College of Physicians
JC10
ACP Journal Club
References 1. National Institute for Health and Care Excellence. Osteoarthritis: care and management in adults. 2014. www.nice. org.uk/guidance/cg177 (accessed 13 May 15) 2. Chou R, Qaseem A, Snow V, et al; Clinical Efficacy Assessment Subcommittee of the American College of Physicians; American College of Physicians; American Pain Society Low Back Pain Guidelines Panel. Diagnosis and treatment of low back pain: a joint clinical practice guideline from the American College of Physicians and the American Pain Society. Ann Intern Med 2007;147:478-91. 3. Wetzel L, Zadrazil M, Paternostro-Sluga T, et al. Intravenous nonopioid analgesic drugs in chronic low back pain patients on chronic opioid treatment: a crossover, randomised, doubleblinded, placebo-controlled study. Eur J Anaesthesiol. 2014; 31:35-40. 4. Ioannidis JP. Contradicted and initially stronger effects in highly cited clinical research. JAMA. 2005;294:218-28. 5. Verkleij SP, Luijsterburg PA, Bohnen AM, Koes BW, Bierma-Zeinstra SM. NSAIDs vs acetaminophen in knee and hip osteoarthritis: a systematic review regarding heterogeneity influencing the outcomes. Osteoarthritis Cartilage. 2011;19: 921-9.
Annals of Internal Medicine
Downloaded From: http://annals.org/pdfaccess.ashx?url=/data/journals/aim/934240/ by a Fudan University User on 01/10/2017
21 Jul 2015
Review: Acetaminophen reduces pain in hip or knee osteoarthritis by a small amount, but not low back pain Clinical impact ratings:
多多多多多夞夞
Machado GC, Maher CG, Ferreira PH, et al. Efficacy and safety of paracetamol for spinal pain and osteoarthritis: systematic review and meta-analysis of randomised placebo controlled trials. BMJ. 2015;350:h1225.
多多多多多多夞
Question
Source of funding: No external funding.
What are the efficacy and safety of acetaminophen (paracetamol) for spinal pain and osteoarthritis (OA) of the hip or knee?
For correspondence: G. C. Machado, The George Institute for Global Health, University of Sydney, Sydney, New South Wales, Australia. E-mail [email protected].
Review scope Included studies compared acetaminophen with placebo in patients with nonspecific spinal pain (neck or low back pain) or OA of the hip or knee. Exclusion criteria were serious pathologic spinal conditions; mixed arthritis populations if data for separate indications were not reported; or immediate analgesia after spinal, hip, or knee surgery. Outcomes included pain, disability, quality of life, adverse events, and abnormal liver enzyme levels (≥ 1.5 times the upper limit of the reference range).
Review methods MEDLINE, EMBASE/Excerpta Medica, AMED, CINAHL, Web of Science, LILACS, International Pharmaceutical Abstracts, and Cochrane Central Register of Controlled Trials (all to Dec 2014), reference lists, relevant Web sites, and clinical trial registries were searched for randomized controlled trials (RCTs). 13 RCTs (n = 5366, mean age range 35 to 70 y) met selection criteria: 10 in patients with OA (n = 3541) and 3 in patients with low back pain (n = 1825). One RCT used IV acetaminophen for chronic low back pain. Acetaminophen dose ranged from 3900 to 4000 mg/d in 10 RCTs and was 3000 mg/d in 3 RCTs. Risk for bias was low for randomization in 4 RCTs; for allocation in 3 RCTs; and for blinding of patients, personnel, and outcome assessors in 12 RCTs. 8 RCTs had immediate outcome assessment (≤ 2 wk), and 9 RCTs had short-term assessment (> 2 wk but ≤ 3 mo); 1 RCT with assessment at 6 months was pooled with short-term RCTs.
Main results The main results are in the Table. Groups did not differ for adverse events, but acetaminophen increased risk for abnormal liver enzyme tests (3 RCTs, n = 1237, relative risk increase 280%, 95% CI 90 to 640).
Conclusion Acetaminophen reduces pain and disability by a small amount in the short term in patients with hip or knee osteoarthritis but not in patients with low back pain.
Commentary Clinical practice guidelines recommend acetaminophen as a first-line medication for spinal pain and OA (1, 2), but the metaanalysis by Machado and colleagues found that the benefits of acetaminophen on short-term pain and disability in patients with OA were below thresholds for clinically important differences. For spinal pain, acetaminophen had essentially no effect. Although evidence on long-term outcomes is lacking, effects would probably not be larger than short-term effects. Acetaminophen did not increase risk for clinical adverse events but increased risk for elevated liver enzymes. Although the systematic review was well done, the evidence base for spinal pain is quite limited: 1 of the 2 trials was small (n = 72), measured only immediate pain relief, and has since been retracted by the authors (3). In addition, the trial evaluated single-dose IV acetaminophen in patients receiving long-term opioids, limiting its generalizability. Initial studies often report results that are subsequently overturned (4), making the findings less than conclusive. For OA, results were based on 3 to 7 trials and were generally consistent, increasing certainty in the findings. The review by Machado and colleagues raises important questions about the role of acetaminophen. For acute spinal pain, future trials should measure analgesia several hours after dosing, which may be the most relevant outcome for patients seeking immediate relief. For OA, head-to-head trials have shown that nonsteroidal antiinflammatory drugs (NSAIDs) are only slightly better than acetaminophen (5). Given its favorable side effect profile and low cost and the potential harms of such alternatives as opioids and NSAIDs, abandoning acetaminophen seems premature, particularly for older adults for whom safe and effective options are limited. However, clinicians prescribing acetaminophen should recognize that benefits are probably small at best. Roger Chou, MD Oregon Health & Science University Portland, Oregon, USA
Acetaminophen vs placebo for low back pain and osteoarthritis of the hip or knee* Outcomes†
Pain
Disability
Indication
Time of assessment‡
Low back pain
Immediate Short-term
1 (1526)
⫺0.5 (⫺2.9 to 1.9)
Osteoarthritis
Immediate
5 (1686)
⫺3.3 (⫺5.8 to ⫺0.8)
Short-term||
7 (2355)
⫺3.7 (⫺5.5 to ⫺1.9)
Immediate
1 (1511)
⫺1.9 (⫺4.8 to 1.0)
Short-term
1 (1522)
0.4 (⫺1.7 to 2.5)
Immediate
3 (1336)
⫺1.7 (⫺6.0 to 2.6)
Short-term||
7 (2354)
⫺2.9 (⫺4.9 to ⫺0.9)
Low back pain
Osteoarthritis
Number of trials (n) 2 (1592)
Weighted mean difference (95% CI)§ 1.4 (⫺1.3 to 4.1)
*Abbreviations defined in Glossary. †Scores for pain and disability were converted to a common scale ranging from 0 (no pain or disability) to 100 (worse pain or disability). ‡Immediate assessment (≤ 2 wk); short-term assessment (> 2 wk but ≤ 3 mo). §Weighted mean difference using a random-effects model. Negative value = improvement with acetaminophen. Minimal clinically important difference = 9 on a 0 to 100 scale. ||Includes 1 trial with assessment at 6 mo (n = 212).
姝 2015 American College of Physicians
JC10
ACP Journal Club
References 1. National Institute for Health and Care Excellence. Osteoarthritis: care and management in adults. 2014. www.nice. org.uk/guidance/cg177 (accessed 13 May 15) 2. Chou R, Qaseem A, Snow V, et al; Clinical Efficacy Assessment Subcommittee of the American College of Physicians; American College of Physicians; American Pain Society Low Back Pain Guidelines Panel. Diagnosis and treatment of low back pain: a joint clinical practice guideline from the American College of Physicians and the American Pain Society. Ann Intern Med 2007;147:478-91. 3. Wetzel L, Zadrazil M, Paternostro-Sluga T, et al. Intravenous nonopioid analgesic drugs in chronic low back pain patients on chronic opioid treatment: a crossover, randomised, doubleblinded, placebo-controlled study. Eur J Anaesthesiol. 2014; 31:35-40. 4. Ioannidis JP. Contradicted and initially stronger effects in highly cited clinical research. JAMA. 2005;294:218-28. 5. Verkleij SP, Luijsterburg PA, Bohnen AM, Koes BW, Bierma-Zeinstra SM. NSAIDs vs acetaminophen in knee and hip osteoarthritis: a systematic review regarding heterogeneity influencing the outcomes. Osteoarthritis Cartilage. 2011;19: 921-9.
Annals of Internal Medicine
Downloaded From: http://annals.org/pdfaccess.ashx?url=/data/journals/aim/934240/ by a Fudan University User on 01/10/2017
21 Jul 2015
