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Topical Nonsteroidal Anti-inflammatory Drugs for Acute Musculoskeletal Pain

Topical Nonsteroidal Anti-inflammatory Drugs for Acute Musculoskeletal Pain Abstract Clinical Question Are topical nonsteroidal anti-inflammatory drugs (NSAIDs) associated with reduced pain intensity in acute musculoskeletal conditions, but without increased adverse events? Bottom Line When treating musculoskeletal conditions such as sprains, strains, and contusions, topical NSAIDs are associated with greater pain relief, but are not associated with an increase in adverse events compared with placebo. This JAMA Clinical Evidence Synopsis summarizes a Cochrane review1 of randomized trials evaluating topical nonsteroidal anti-inflammatory drugs (NSAIDs) to treat musculoskeletal conditions, such as sprains, strains, and contusions. Topical NSAIDs are applied directly to the skin over the painful area and must cross the skin and penetrate underlying tissues to reach the site of action. Systemic uptake is minimal, potentially limiting systemic adverse events, particularly gastrointestinal effects. The review included 47 studies from an earlier review in 20102 and 14 new studies. Twenty unpublished studies (4403 participants) were identified for which results were unavailable. Box Section Ref ID Evidence Profile No. of studies overall: 61 (22 involving diclofenac, ibuprofen, and ketoprofen) No. of randomized clinical trials: 61 Study years: Conducted, approximately 1970-2011; published 1977-2013; date of last literature search: February 2015 No. of patients: 8644 (3064 involving diclofenac, ibuprofen, and ketoprofen) Men: 54% (4668) Women: 46% (3976) Race/ethnicity: Not available (mostly European studies) Age, mean (range): 35 years (11 to 89 years; majority >18 years) Settings: Outpatients with acute musculoskeletal pain, primarily uncomplicated sprains, strains, and contusions Countries: Argentina, Belgium, Denmark, Finland, France, Germany, Hungary, Italy, Japan, New Zealand, Sweden, Switzerland, United Kingdom, and the United States Comparisons: Topical nonsteroidal anti-inflammatory drug (NSAID) vs topical placebo (without NSAID), another topical NSAID, or oral NSAID Primary outcome: Clinical success at 7 days (predefined efficacy outcomes important to patients: reduction of ≥50% in pain intensity, no or mild pain, and patient global assessments of “very good or excellent”) Secondary outcomes: The numbers of participants experiencing any local adverse event, any systemic adverse event, or withdrawing from the study (any cause, lack of efficacy, or adverse events) Summary of Findings Formulations of topical diclofenac, ibuprofen, ketoprofen, piroxicam, and indomethacin were associated with higher rates of clinical success than matching topical placebo (Table). For topical diclofenac, 800 of 1074 participants (74%) experienced “clinical success” overall (number needed to treat [NNT], 3.7; 95% CI, 3.2-4.3); however, some gel and plaster formulations provided better results than others. One branded diclofenac gel had an NNT of 1.8 (95% CI, 1.5-2.1) (152/196; 78%). For topical ketoprofen, 251 of 346 participants (73%) experienced clinical success overall (NNT, 3.9; 95% CI, 3.0-5.3), with gel formulations providing the best results (129 of 178 participants [72%]; NNT, 2.5; 95% CI, 2.0-3.4). For topical ibuprofen gel, 50 of 120 participants (42%) experienced clinical success (NNT, 3.9; 95% CI, 2.7-6.7). All other drugs in any formulation had NNT values above 4. Benzydamine did not differ from placebo (74/96 [77%] vs 65/97 [67%]). Local skin reactions associated with topical NSAIDs (155/3619 participants; 4.3%) did not differ from placebo (145/3121; 4.6%) and were generally mild and transient. Systemic adverse events occurred in 3% of participants with both NSAIDs and placebo (92/2956 vs 91/2620, respectively). Withdrawals due to adverse events were uncommon (1% of all participants, 33/3365 with NSAIDs vs 30/3040 with placebo). Discussion Topical NSAIDs are associated with good pain relief (pain relieved by 50% or better, patient report of “very good or excellent”) for acute musculoskeletal pain primarily due to sprains, strains, and overuse injuries. Gel formulations of diclofenac, ibuprofen, and ketoprofen as well as some diclofenac patches are associated with the largest number of people achieving good pain relief. Topical NSAIDs are not associated with increased local skin reactions compared with inert carrier (placebo), although the carrier may cause mild, transient irritation. Systemic problems (mainly gastrointestinal) commonly seen with oral NSAIDs were infrequent in study participants. However, topical NSAIDs are useful for those individuals unable to tolerate oral NSAIDs or for whom oral NSAIDs are contraindicated. Limitations Most participants were young, otherwise healthy adults. There were insufficient data to reliably compare individual topical NSAIDs with each other or with the same oral NSAID. The dose of NSAID used was often difficult to determine, and appeared to vary considerably between studies of the same drug. Many older studies (mainly using NSAIDs other than diclofenac, ibuprofen, and ketoprofen) were small and of poor reporting quality, used less stringent and well-defined outcomes, and may have used formulations no longer available or relevant to clinical practice. Comparison of Findings With Current Practice Guidelines Guidelines generally recommend physical management, such as protect, rest, ice, compression, and elevation, some acknowledging that analgesia (unspecified) may be necessary. Recent guidelines recommend topical NSAIDs among several analgesic options.3-5 Areas in Need of Future Study Future studies should use clearly defined, clinically useful, treatment goals rather than average results (eg, patients with no or mild pain6 after 3 or 7 days) and provide information about formulation and dose. Studies including older people would clarify utility in a population likely to benefit most from the favorable adverse event profile. Section Editor: Mary McGrae McDermott, MD, Senior Editor. Submissions: We encourage authors to submit papers for consideration as a JAMA Clinical Evidence Synopsis. Please contact Dr McDermott at mdm608@northwestern.edu. Back to top Article Information Corresponding Author: Sheena Derry, MA, Pain Research, Churchill Hospital, Oxford OX3 7LE, England (sheena.derry@ndcn.ox.ac.uk). Conflict of Interest Disclosures: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported. Dr Moore reported receiving a grant and personal fees from Reckitt Benckiser and personal fees from Menarini. No other disclosures were reported. References 1. Derry S, Moore RA, Gaskell H, McIntyre M, Wiffen PJ. Topical NSAIDs for acute musculoskeletal pain in adults. Cochrane Database Syst Rev. 2015;6:CD007402.PubMedGoogle Scholar 2. Massey T, Derry S, Moore RA, McQuay HJ. Topical NSAIDs for acute pain in adults. Cochrane Database Syst Rev. 2010;(6):CD007402.PubMedGoogle Scholar 3. University of Saskatchewan. Musculoskeletal strains and sprains: guidelines for prescribing NSAIDs. http://medsask.usask.ca/professional/guidelines/musculoskeletal-strains-and-sprains.php. Accessed January 27, 2016. 4. Roosen P, Willems T, De Ridder R, et al. Ankle sprains: diagnosis and therapy. https://kce.fgov.be/sites/default/files/page_documents/KCE_197C_2011-02-GCP_Ankle%20sprain_0.pdf. Accessed January 27, 2016. 5. National Institute for Health and Care Excellence. Clinical Knowledge Summaries: sprains and strains. http://clarity.co.uk/contact/. Accessed January 27, 2016. 6. Moore RA, Straube S, Aldington D. Pain measures and cut-offs—“no worse than mild pain” as a simple, universal outcome. Anaesthesia. 2013;68(4):400-412.PubMedGoogle ScholarCrossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png JAMA American Medical Association

Topical Nonsteroidal Anti-inflammatory Drugs for Acute Musculoskeletal Pain

JAMA , Volume 315 (8) – Feb 23, 2016

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Publisher
American Medical Association
Copyright
Copyright © 2016 American Medical Association. All Rights Reserved.
ISSN
0098-7484
eISSN
1538-3598
DOI
10.1001/jama.2016.0249
Publisher site
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Abstract

Abstract Clinical Question Are topical nonsteroidal anti-inflammatory drugs (NSAIDs) associated with reduced pain intensity in acute musculoskeletal conditions, but without increased adverse events? Bottom Line When treating musculoskeletal conditions such as sprains, strains, and contusions, topical NSAIDs are associated with greater pain relief, but are not associated with an increase in adverse events compared with placebo. This JAMA Clinical Evidence Synopsis summarizes a Cochrane review1 of randomized trials evaluating topical nonsteroidal anti-inflammatory drugs (NSAIDs) to treat musculoskeletal conditions, such as sprains, strains, and contusions. Topical NSAIDs are applied directly to the skin over the painful area and must cross the skin and penetrate underlying tissues to reach the site of action. Systemic uptake is minimal, potentially limiting systemic adverse events, particularly gastrointestinal effects. The review included 47 studies from an earlier review in 20102 and 14 new studies. Twenty unpublished studies (4403 participants) were identified for which results were unavailable. Box Section Ref ID Evidence Profile No. of studies overall: 61 (22 involving diclofenac, ibuprofen, and ketoprofen) No. of randomized clinical trials: 61 Study years: Conducted, approximately 1970-2011; published 1977-2013; date of last literature search: February 2015 No. of patients: 8644 (3064 involving diclofenac, ibuprofen, and ketoprofen) Men: 54% (4668) Women: 46% (3976) Race/ethnicity: Not available (mostly European studies) Age, mean (range): 35 years (11 to 89 years; majority >18 years) Settings: Outpatients with acute musculoskeletal pain, primarily uncomplicated sprains, strains, and contusions Countries: Argentina, Belgium, Denmark, Finland, France, Germany, Hungary, Italy, Japan, New Zealand, Sweden, Switzerland, United Kingdom, and the United States Comparisons: Topical nonsteroidal anti-inflammatory drug (NSAID) vs topical placebo (without NSAID), another topical NSAID, or oral NSAID Primary outcome: Clinical success at 7 days (predefined efficacy outcomes important to patients: reduction of ≥50% in pain intensity, no or mild pain, and patient global assessments of “very good or excellent”) Secondary outcomes: The numbers of participants experiencing any local adverse event, any systemic adverse event, or withdrawing from the study (any cause, lack of efficacy, or adverse events) Summary of Findings Formulations of topical diclofenac, ibuprofen, ketoprofen, piroxicam, and indomethacin were associated with higher rates of clinical success than matching topical placebo (Table). For topical diclofenac, 800 of 1074 participants (74%) experienced “clinical success” overall (number needed to treat [NNT], 3.7; 95% CI, 3.2-4.3); however, some gel and plaster formulations provided better results than others. One branded diclofenac gel had an NNT of 1.8 (95% CI, 1.5-2.1) (152/196; 78%). For topical ketoprofen, 251 of 346 participants (73%) experienced clinical success overall (NNT, 3.9; 95% CI, 3.0-5.3), with gel formulations providing the best results (129 of 178 participants [72%]; NNT, 2.5; 95% CI, 2.0-3.4). For topical ibuprofen gel, 50 of 120 participants (42%) experienced clinical success (NNT, 3.9; 95% CI, 2.7-6.7). All other drugs in any formulation had NNT values above 4. Benzydamine did not differ from placebo (74/96 [77%] vs 65/97 [67%]). Local skin reactions associated with topical NSAIDs (155/3619 participants; 4.3%) did not differ from placebo (145/3121; 4.6%) and were generally mild and transient. Systemic adverse events occurred in 3% of participants with both NSAIDs and placebo (92/2956 vs 91/2620, respectively). Withdrawals due to adverse events were uncommon (1% of all participants, 33/3365 with NSAIDs vs 30/3040 with placebo). Discussion Topical NSAIDs are associated with good pain relief (pain relieved by 50% or better, patient report of “very good or excellent”) for acute musculoskeletal pain primarily due to sprains, strains, and overuse injuries. Gel formulations of diclofenac, ibuprofen, and ketoprofen as well as some diclofenac patches are associated with the largest number of people achieving good pain relief. Topical NSAIDs are not associated with increased local skin reactions compared with inert carrier (placebo), although the carrier may cause mild, transient irritation. Systemic problems (mainly gastrointestinal) commonly seen with oral NSAIDs were infrequent in study participants. However, topical NSAIDs are useful for those individuals unable to tolerate oral NSAIDs or for whom oral NSAIDs are contraindicated. Limitations Most participants were young, otherwise healthy adults. There were insufficient data to reliably compare individual topical NSAIDs with each other or with the same oral NSAID. The dose of NSAID used was often difficult to determine, and appeared to vary considerably between studies of the same drug. Many older studies (mainly using NSAIDs other than diclofenac, ibuprofen, and ketoprofen) were small and of poor reporting quality, used less stringent and well-defined outcomes, and may have used formulations no longer available or relevant to clinical practice. Comparison of Findings With Current Practice Guidelines Guidelines generally recommend physical management, such as protect, rest, ice, compression, and elevation, some acknowledging that analgesia (unspecified) may be necessary. Recent guidelines recommend topical NSAIDs among several analgesic options.3-5 Areas in Need of Future Study Future studies should use clearly defined, clinically useful, treatment goals rather than average results (eg, patients with no or mild pain6 after 3 or 7 days) and provide information about formulation and dose. Studies including older people would clarify utility in a population likely to benefit most from the favorable adverse event profile. Section Editor: Mary McGrae McDermott, MD, Senior Editor. Submissions: We encourage authors to submit papers for consideration as a JAMA Clinical Evidence Synopsis. Please contact Dr McDermott at mdm608@northwestern.edu. Back to top Article Information Corresponding Author: Sheena Derry, MA, Pain Research, Churchill Hospital, Oxford OX3 7LE, England (sheena.derry@ndcn.ox.ac.uk). Conflict of Interest Disclosures: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported. Dr Moore reported receiving a grant and personal fees from Reckitt Benckiser and personal fees from Menarini. No other disclosures were reported. References 1. Derry S, Moore RA, Gaskell H, McIntyre M, Wiffen PJ. Topical NSAIDs for acute musculoskeletal pain in adults. Cochrane Database Syst Rev. 2015;6:CD007402.PubMedGoogle Scholar 2. Massey T, Derry S, Moore RA, McQuay HJ. Topical NSAIDs for acute pain in adults. Cochrane Database Syst Rev. 2010;(6):CD007402.PubMedGoogle Scholar 3. University of Saskatchewan. Musculoskeletal strains and sprains: guidelines for prescribing NSAIDs. http://medsask.usask.ca/professional/guidelines/musculoskeletal-strains-and-sprains.php. Accessed January 27, 2016. 4. Roosen P, Willems T, De Ridder R, et al. Ankle sprains: diagnosis and therapy. https://kce.fgov.be/sites/default/files/page_documents/KCE_197C_2011-02-GCP_Ankle%20sprain_0.pdf. Accessed January 27, 2016. 5. National Institute for Health and Care Excellence. Clinical Knowledge Summaries: sprains and strains. http://clarity.co.uk/contact/. Accessed January 27, 2016. 6. Moore RA, Straube S, Aldington D. Pain measures and cut-offs—“no worse than mild pain” as a simple, universal outcome. Anaesthesia. 2013;68(4):400-412.PubMedGoogle ScholarCrossref

Journal

JAMAAmerican Medical Association

Published: Feb 23, 2016

Keywords: anti-inflammatory agents, non-steroidal,musculoskeletal pain,analgesics, topical,sprains and strains,contusions,musculoskeletal diseases,adverse event,pain

References