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BMC Primary Care

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Open Access 01-12-2004 | Research article

Topical NSAIDs for acute pain: a meta-analysis

Authors: Lorna Mason, R Andrew Moore, Jayne E Edwards, Sheena Derry, Henry J McQuay

Published in: BMC Primary Care | Issue 1/2004

Abstract

Background

A previous systematic review reported that topical NSAIDs were effective in relieving pain in acute conditions like sprains and strains, with differences between individual drugs for efficacy. More trials, a better understanding of trial quality and bias, and a reclassification of certain drugs necessitate a new review.

Methods

Studies were identified by searching electronic databases and writing to manufacturers. We selected randomised double blind trials comparing topical NSAID with either placebo or another active treatment in adults with acute pain, and extracted dichotomous information approximating to a 50% reduction in pain at one week, together with details of adverse events and withdrawals. Relative benefit and number-needed-to-treat (NNT), and relative risk and number-needed-to-harm (NNH) were calculated, with sensitivity analyses where appropriate to investigate differences between individual drugs and aspects of trial design.

Results

Twenty-six double blind placebo controlled trials had information from 2,853 patients for evaluation of efficacy. Topical NSAID was significantly better than placebo in 19 of the 26 trials, with a pooled relative benefit of 1.6 (95% confidence interval 1.4 to 1.7), and NNT of 3.8 (95% confidence interval 3.4 to 4.4) compared with placebo for the outcome of half pain relief at seven days. Results were not affected by outcome reported, or condition treated, but smaller trials yielded a larger estimate of efficacy. Indirect comparisons of individual topical NSAIDs showed that ketoprofen was significantly better than all other topical NSAIDs, while indomethacin was barely distinguished from placebo. Three trials, with 433 patients, compared topical with oral NSAID (two trials compared the same drug, one compared different drugs) and found no difference in efficacy. Local adverse events, systemic adverse events, or withdrawals due to an adverse event were rare, and no different between topical NSAID and placebo.

Conclusions

Topical NSAIDs were effective and safe in treating acute painful conditions for one week.

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Moore RA, Tramer MR, Carroll D, Wiffen PJ, McQuay HJ: Quantitative systematic review of topically applied non-steroidal anti-inflammatory drugs. BMJ. 1998, 316: 333-338.CrossRefPubMedPubMedCentral

Begg C, Cho M, Eastwood S, Horton R, Moher D, Olkin I, Pitkin R, Rennie D, Schulz KF, Simel D, Stroup DF: Improving the quality of reporting of randomized controlled trials. The CONSORT statement. JAMA. 1996, 276: 637-639. 10.1001/jama.276.8.637.CrossRefPubMed

Moher D, Pham B, Jones A, Cook DJ, Jadad AR, Moher M, Tugwell P, Klassen TP: Does quality of reports of randomised trials affect estimates of intervention efficacy reported in meta-analyses?. Lancet. 1998, 352: 609-613. 10.1016/S0140-6736(98)01085-X.CrossRefPubMed

Moore RA, Gavaghan D, Tramer MR, Collins SL, McQuay HJ: Size is everything--large amounts of information are needed to overcome random effects in estimating direction and magnitude of treatment effects. Pain. 1998, 78: 209-216. 10.1016/S0304-3959(98)00140-7.CrossRefPubMed

Li Wan Po A: PJ Practice Checklist: Topical Analgesics. The Pharmaceutical Journal. 1996

British National Formulary No 45. 2003, London: British Medical Association, Royal Pharmaceutical Society

Martindale: the extra pharmacopoeia. Edited by: Reynolds JEF. 1999, London: Royal Pharmaceutical Society, 32

Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, McQuay HJ: Assessing the quality of reports of randomized clinical trials: is blinding necessary?. Control Clin Trials. 1996, 17: 1-12. 10.1016/0197-2456(95)00134-4.CrossRefPubMed

Smith LA, Oldman AD, McQuay HJ, Moore RA: Teasing apart quality and validity in systematic reviews: an example from acupuncture trials in chronic neck and back pain. Pain. 2000, 86: 119-132. 10.1016/S0304-3959(00)00234-7.CrossRefPubMed

10.

Cook RJ, Sackett DL: The number needed to treat: a clinically useful measure of treatment effect. BMJ. 1995, 310: 452-454.CrossRefPubMedPubMedCentral

11.

Morris JA, Gardner MJ: Calculating confidence intervals for relative risk, odds ratios and standardised ratios and rates. In Statistics with confidence – confidence intervals and statistical guidelines. Edited by: Gardner MJ, Altman DG. 1995, London: British Medical Journal, 50-63.

12.

L'Abbe KA, Detsky AS, O'Rourke K: Meta-analysis in clinical research. Ann Intern Med. 1987, 107: 224-233.CrossRefPubMed

13.

Gavaghan DJ, Moore RA, McQuay HJ: An evaluation of homogeneity tests in meta-analyses in pain using simulations of individual patient data. Pain. 2000, 85: 415-424. 10.1016/S0304-3959(99)00302-4.CrossRefPubMed

14.

Higgins J, Thompson S, Deeks J, Altman D: Statistical heterogeneity in systematic reviews of clinical trials: a critical appraisal of guidelines and practice. J Health Serv Res Policy. 2002, 7: 51-61. 10.1258/1355819021927674.CrossRefPubMed

15.

Tramer MR, Reynolds DJ, Moore RA, McQuay HJ: Impact of covert duplicate publication on meta-analysis: a case study. BMJ. 1997, 315: 635-640.CrossRefPubMedPubMedCentral

16.

Moher D, Cook DJ, Eastwood S, Olkin I, Rennie D, Stroup DF: Improving the quality of reports of meta-analyses of randomised controlled trials: the QUOROM statement. Quality of reporting of meta-analyses. Lancet. 1999, 354: 1896-1900. 10.1016/S0140-6736(99)04149-5.CrossRefPubMed

17.

Predel: Diclofenac patch for topical treatment of acute impact injuries: a randomised, double blind, placebo controlled, multicentre study. Supplied by Novartis.

18.

Airaksinen O, Venäläinen J, Pietiläinen T: Ketoprofen 2.5% gel versus placebo gel in the treatment of acute soft tissue injuries. Int J Clin Pharmacol Ther Toxicol. 1993, 31: 561-563.PubMed

19.

Auclair J, Georges M, Grapton X, Gryp L, D'Hooghe M, Meisser RG, Noto R, Schmidtmayer B: A double-blind controlled multi-center study of percutaneous niflumic acid gel and placebo in the treatment of achilles heel tendinitis. Curr Ther Res. 1989, 46: 782-788.

20.

Baracchi G, Messina Denaro S, Piscini S: Experience of the topical use of isobutylfenylproprionic acid (Ibuprofen) in traumatic inflammation. A double-blind comparison with placebo. Gazz Med Ital. 1982, 141: 691-694.

21.

Billigman PW: Therapie von Sprunggelenks-distosionen mit ibuprofen-mikrogel. Therapiewoche. 1996, 21: 1187-1192.

22.

Campbell J, Dunn T: Evaluation of topical ibuprofen cream in the treatment of acute ankle sprains. J Accid Emerg Med. 1994, 11: 178-182.CrossRefPubMedPubMedCentral

23.

Dreiser RL: Clinical trial of efficacy and tolerability of topical ibuprofen in the treatment of tendinitis. Le Journal International De Médecine. 1988, 119: 15-31.

24.

Dreiser RL: Clinical trial – Fatsum gel FG-6. Supplied by Menarini. 1989,

25.

Dreiser RE, Charlot J, Lopez A, Ditisheim A: Clinical evaluation of niflumic acid gel in the treatment of uncomplicated ankle sprains. Curr Med Res Opin. 1990, 12: 93-99.CrossRefPubMed

26.

Dreiser RL, Roche R, de Sahb R, Thomas F, Leutenegger E: Flurbiprofen local action transcutaneous (LAT™): Clinical evaluation in the treatment of acute ankle sprains. Eur J Rheumatol Inflamm. 1994, 14: 9-13.PubMed

27.

Galer BS, Rowbotham M, Perander J, Devers A, Friedman E: Topical diclofenac patch relieves minor sports injury pain: results of a multicenter controlled clinical trial. J Pain Symptom Manage. 2000, 19: 287-294. 10.1016/S0885-3924(00)00125-1.CrossRefPubMed

28.

Julien D: Clinical trial – Fastum gel FG-8. Supplied by Menarini. 1989,

29.

Kockelbergh M, Verspeelt P, Caloine R, Dermaux F: Local anti inflammatory treatment with a ketoprofen gel: current clinical findings. J Belg Med Phys Rehabil. 1985, 8: 205-213.

30.

Machen J, Whitefield M: Efficacy of a proprietary ibuprofen gel in soft tissue injuries: a randomised, double blind placebo controlled study. Int J Clin Pharmacol. 2002, 56: 102-106.

31.

McLatchie GR, McDonald M, Lawrence GF, Rogmans D, Lisai P, Hibberd M: Soft tissue trauma: a randomised controlled trial of the topical application of felbinac, a new NSAID. Br J Clin Pract. 1989, 43: 277-280.PubMed

32.

Morris WD, Scott HV, Peters WA, Ketelbey JW: Felbinac topical gel for acute soft tissue sports injuries. N Z J Sports Med. 1991, 19: 45-47.

33.

Noret A, Roty V, Allington N, Hauters P, Zuinen C, Poels R: Ketoprofen gel as topical treatment for sport injuries. Acta Ther. 1987, 13: 367-378.

34.

Parrini M, Cabitza P, Arrigo A, Vanasia M: Efficacy and tolerability of ketoprofen lysine salt foam for topical use in the treatment of traumatic pathologies of the locomotor apparatus. Clin Ter. 1992, 141: 199-204.PubMed

35.

Ramesh N, Steuber U: Dolgit^® cream in accident- and sports-related injuries in medical practice. Results of a double blind study. Therapiewoche. 1983, 33: 4563-4570.

36.

Russell AL: Piroxicam 0.5% topical gel compared to placebo in the treatment of acute soft tissue injuries: a double-blind study comparing efficacy and safety. Clin Invest Med. 1991, 14: 35-43.PubMed

37.

Sanguinetti C: Trattemento con BPAA gel dei traumi dei tessuti moli. Clin Ter. 1989, 130: 255-258.PubMed

38.

Sinniger M, Blanchard P: Controlled clinical trial with Fentiazac cream in sport microtraumatology. J Int Med Res. 1981, 9: 300-302.PubMed

39.

Thorling J, Linden B, Berg R, Sandahl A: A double blind comparison of naproxen gel and placebo in the treatment of soft tissue injuries. Curr Med Res Opin. 1990, 12: 242-248.CrossRefPubMed

40.

Vecchiet L, Colozzi A: Effects of meclofenamic acid in the treatment of lesions deriving from minor traumatology. Clin J Pain. 1991, 7 (Suppl 1): S54-S59.CrossRefPubMed

41.

Battista Curioni G, Domenica FD, Daolio P, Spignoli G: Valutazione dell'efficacia terapeutica di ibudros gel in traumatologia. Clin Eur. 1985, 24: 456-460.

42.

Governali E, Casalini D: Ricerda clinica controllata tra ketoprofene gel 5% e ketoprofene crema 1% in pazienti con postumi di lesioni traumatiche. Riabilitazione. 1995, 28: 61-69.

43.

Gualdi A, Bonollo L, Martini A, Forgione A: Antinflammatori no steroidi per uso topico in traumatologia: studio clinico con flunoxaprofene e chetoprofene. Riforma Med. 1987, 102: 401-404.

44.

Hosie GAC: The topical NSAID, felbinac, versus oral ibuprofen: a comparison of efficacy in the treatment of acute lower back injury. Br J Clin Res. 1993, 4: 5-17.

45.

Picchio AA, Volta S, Longoni A: Studio clinico controllato sull'impiego dell'ibuprofen per uso topico in traumatologica sportiva. Med Sport. 1981, 34: 403-406.

46.

Sugioka Y: Multicenter clinical evaluation of piroxicam gel vs. indomethacin gel in the treatment of non-traumatic diseases of tendon or muscle. Jap Pharmacol Ther. 1984, 12: 139-153.

47.

Tonutti A: The use of ketoprofen gel 5% (orudis gel) in traumatology: controlled double-blind study vs etofenamate. Ort Traum Oggi. 1994, 14: 119-125.

48.

Whitefield M, O'Kane CJA, Anderson S: Comparative efficacy of a proprietary topical ibuprofen gel and oral ibuprofen in acute soft tissue injuries: a randomised, double blind study. J Clin Pharm Ther. 2002, 27: 409-417. 10.1046/j.1365-2710.2002.00439.x.CrossRefPubMed

49.

Åkermark C, Forsskåhl B: Topical indomethacin in overuse injuries in athletes. A randomized double blind study comparing Elmetacin^® with oral indomethacin and placebo. Int J Sports Med. 1990, 11: 393-396.CrossRefPubMed

50.

Aoki T, et al: Comparative study of piroxicam gel with indomethacin gel and piroxicam placebo gel in the treatment of pain from orthopedic trauma. Jap Pharmacol Ther. 1984, 12: 101-117.

51.

Diebschlag W, Nocker W, Bullingham R: A double-blind study of the efficacy of topical ketorolac tromethamine gel in the treatment of ankle sprain, in comparison to placebo and etofenamate. J Clin Pharmacol. 1990, 30: 82-89.CrossRefPubMed

52.

Fujimaki E, et al: Clinical evaluation of piroxicam gel versus indomethacin gel and placebo in the treatment of muscle pain: a double-blind, multicenter study. Jap Pharmacol Ther. 1985, 12: 119-137.

53.

Terrin N, Schmid CH, Lau J, Olkin I: Adjusting for publication bias in the presence of heterogeneity. Stat Med. 2003, 22: 2113-2126. 10.1002/sim.1461.CrossRefPubMed

54.

MacLean CH, Morton SC, Ofman JJ, Roth EA, Shekelle PG: How useful are unpublished data from the Food and Drug Administration in meta-analysis?. J Clin Epidemiol. 2003, 56: 44-51. 10.1016/S0895-4356(02)00520-6.CrossRefPubMed

55.

Egger M, Juni P, Bartlett C, Holenstein F, Sterne J: How important are comprehensive literature searches and the assessment of trial quality in systematic reviews. Empirical study. Health Technol Assess. 2003, 7: 1-76.PubMed

56.

Burdett S, Stewart LA, Tierney JF: Publication bias and meta-analyses: a practical example. Int J Technol Assess Health Care. 2003, 19: 129-134. 10.1017/S0266462303000126.CrossRefPubMed

57.

Kalso E, Moore RA: Five easy pieces on evidence-based medicine (2). Eur J Pain. 2000, 4: 321-324. 10.1053/eujp.2000.0191.CrossRefPubMed

58.

Marjoribanks J, Proctor M, Farquhar C: Nonsteroidal anti-inflammatory drugs for primary dysmenorrhoea. Cochrane Database Syst Rev. 2003, 4: CD001751-PubMed

59.

Towheed T, Shea B, Wells G, Hochberg M: Analgesia and non-aspirin, non-steroidal anti-inflammatory drugs for osteoarthritis of the hip. Cochrane Database Syst Rev. 2000, 2: CD000517-PubMed

60.

Watson MC, Brookes ST, Kirwan JR, Faulkner A: Non-aspirin, non-steroidal anti-inflammatory drugs (NSAIDS) for osteoarthritis of the knee. Cochrane Database Syst Rev. 2000, 2: CD000142-PubMed

61.

Evans JM, McMahon AD, McGilchrist MM, White G, Murray FE, McDevitt DG, MacDonald TM: Topical non-steroidal anti-inflammatory drugs and admission to hospital for upper gastrointestinal bleeding and perforation: a record linkage case-control study. BMJ. 1995, 311: 22-26.CrossRefPubMedPubMedCentral

62.

Evans JM, McGregor E, McMahon AD, McGilchrist MM, Jones MC, White G, McDevitt DG, MacDonald TM: Non-steroidal anti-inflammatory drugs and hospitalization for acute renal failure. QJM. 1995, 88: 551-557.PubMed

The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2296/5/10/prepub

Title: Topical NSAIDs for acute pain: a meta-analysis
Authors: Lorna Mason
R Andrew Moore
Jayne E Edwards
Sheena Derry
Henry J McQuay
Publication date: 01-12-2004
Publisher: BioMed Central
Published in: BMC Primary Care / Issue 1/2004
Electronic ISSN: 2731-4553
DOI: https://doi.org/10.1186/1471-2296-5-10

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Topical NSAIDs for acute pain: a meta-analysis

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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