Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
BMC Musculoskeletal Disorders
Published in: BMC Musculoskeletal Disorders 1/2004

Open Access 01-12-2004 | Research article

Topical NSAIDs for chronic musculoskeletal pain: systematic review and meta-analysis

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

Published in: BMC Musculoskeletal Disorders | Issue 1/2004

Login to get access

Abstract

A previous systematic review reported that topical NSAIDs were effective in relieving pain in chronic conditions like osteoarthritis and tendinitis. 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 identified randomised, double blind trials comparing topical NSAID with either placebo or another active treatment, in adults with chronic pain. The primary outcome was a reduction in pain of approximately 50% at two weeks, and secondary outcomes were local and systemic adverse events and adverse event-related withdrawals. Relative benefit and number-needed-to-treat (NNT), and relative harm and number-needed-to-harm (NNH) were calculated, and the effects of trial quality, validity and size, outcome reported, and condition treated, were examined by sensitivity analyses.

Results

Twelve new trials were added to 13 trials from a previous review. Fourteen double blind placebo-controlled trials had information from almost 1,500 patients. Topical NSAID was significantly better than placebo with relative benefit 1.9 (95% confidence interval 1.7 to 2.2), NNT 4.6 (95% confidence interval 3.8 to 5.9). Results were not affected by trial quality, validity or size, outcome reported, or condition treated. Three trials with 764 patients comparing a topical with an oral NSAID found no difference in efficacy. Local adverse events (6%), systemic adverse events (3%), or the numbers withdrawing due to an adverse event were the same for topical NSAID and placebo.

Conclusions

Topical NSAIDs were effective and safe in treating chronic musculoskeletal conditions for two weeks. Larger and longer trials are necessary to fully elucidate the place of topical NSAIDs in clinical practice.
Appendix
Available only for authorised users
Literature
1.
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
2.
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
3.
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
4.
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
5.
6.
British National Formulary No 45. 2003, London: British Medical Association, Royal Pharmaceutical Society
7.
Martindale: the extra pharmacopoeia. Edited by: Reynolds JEF. 1999, London: Royal Pharmaceutical Society, 32
8.
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
9.
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.
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.
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.
Bolten W: Felbinac-Gel zur Behandlung lokalisierter extraartikulärer rheumatischer Beschwerden – eine multizentrische, placebokontrollierte, randomisierte Studie. [Felbinac gel for treatment of localized extra-articular rheumatic diseases – a multicenter, placebo controlled, randomized study]. Z Rheumatol. 1991, 50: 109-113.PubMed
18.
Brühlmann P, Michel BA: Topical diclofenac patch in patients with knee osteoarthritis: a randomized, double-blind, controlled clinical trial. Clin Exp Rheumatol. 2003, 21: 193-198.PubMed
19.
Dreiser RL, Tisne-Camus M: DHEP plasters as a topical treatment of knee osteoarthritis – a double-blind placebo-controlled study. Drugs Exp Clin Res. 1993, 19: 117-123.PubMed
20.
Fotiades P, Bach GL: Wirkung einer flufenaminsaurehaltigen Salbe bei verschiedenen rheumatischen Erkrankungen. [The effect of a flufenamic acid containing ointment in various rheumatic diseases. A double blind study]. Fortschr Med. 1976, 94: 1036-1038.PubMed
21.
Galeazzi M, Marcolongo R: A placebo-controlled study of the efficacy and tolerability of a nonsteroidal anti-inflammatory drug, DHEP plaster, in inflammatory peri- and extra-articular rheumatological diseases. Drugs Exp Clin Res. 1993, 19: 107-115.PubMed
22.
Ginsberg F, Famaey JP: Double-blind, randomized crossover study of the percutaneous efficacy and tolerability of a topical indomethacin spray versus placebo in the treatment of tendinitis. J Int Med Res. 1991, 19: 131-136.PubMed
23.
Grace D, Rogers J, Skeith K, Anderson K: Topical diclofenac versus placebo: a double blind, randomized clinical trial in patients with osteoarthritis of the knee. J Rheumatol. 1999, 26: 2659-2663.PubMed
24.
Gui L, Pellacci F, Ghirardini G: Impiego dell'ibuprofen crema in pazienti ambulatoriali di interesse ortopedico. Confronto in doppia cecità con placebo. [Use of ibuprofen cream in ambulatory orthopedic patients. Double blind comparison with placebo]. Clin Ter. 1982, 101: 363-369.PubMed
25.
Hohmeister R: Die Behandlung von weichteilrheumatischen Erkrankungen mit Mobilisin Gel. Resultate einer Doppelblind-Studie. [Treatment of rheumatic diseases of soft tissues with Mobilisin Gel. Results of a double blind study]. Fortschr Med. 1983, 101: 1586-1588.PubMed
26.
Link R, Balint G, Pavlik G, Otto J, Krause W: Topische Behandlung von Weichteil-rheumatismus und Sportverletzungen. Wirksamkeit und Verträglichkeit eines neuen Ketoprofengels. [Topical treatment of soft tissue rheumatism and athletic injuries. Effectiveness and tolerance of a new ketoprofen gel]. Fortschr Med. 1996, 114: 311-314.PubMed
27.
Mattara L, Trotta F, Biasi D, Cervetti R: Evaluation of the efficacy and tolerability of a new locally acting preparation of flurbiprofen in scapulohumeral periarthritis. Eur J Rheumatol Inflamm. 1994, 4: 15-20.
28.
Poul J, West J, Buchanan N, Grahame R: Local action transcutaneous flurbipofen in the treatment of soft tissue rheumatism. Br J Rheumatol. 1993, 32: 1000-1003.CrossRefPubMed
29.
Rose W, Manz G, Lemmel EM: Behandlung der aktivierten gonarthrose mit topisch appliziertem piroxicam-gel. [Topical application of Piroxicam-gel in the treatment of activated gonarthrosis]. Münch Med Wschr. 1991, 133: 562-566.
30.
Roth SH: A controlled clinical investigation of 3% diclofenac/2.5% sodium hyaluronate topical gel in the treatment of uncontrolled pain in chronic oral NSAID users with osteoarthritis. Int J Tissue React. 1995, 4: 129-132.
31.
Rovensky J, Micekova D, Gubzova Z, Fimmers R, Lenhard G, Vogtle-Junkert U, Schreyger F: Treatment of knee osteoarthritis with a topical non-steroidal antiinflammatory drug. Results of a randomized, double-blind, placebo-controlled study on the efficacy and safety of a 5% ibuprofen cream. Drugs Exp Clin Res. 2001, 27: 209-221.PubMed
32.
Balthazar-Letawe D: Voltaren Emulgel en pratique rhumatologique. Essai comparatif avec Indocid gel. [Voltaren Emugel in clinical rheumatology. Comparative trial with Indocid gel]. Acta Belg Med Phys. 1987, 10: 109-110.PubMed
33.
Burgos A, Busquier MP, Reino JG, Ferreiro JL, Navarro F, Valverde J, Moreno E: Double-blind, double-dummy comparative study of local action transcutaneous flurbiprofen (flurbiprofen LAT) versus piketoprofen cream in the treatment of extra-articular rheumatism. Clin Drug Invest. 2001, 21: 95-102.CrossRef
34.
Dickson DJ: A double-blind evaluation of topical piroxicam gel with oral ibuprofen in osteoarthritis of the knee. Curr Ther Res. 1991, 49: 199-207.
35.
Geller O: Vergleich eines Salizylat/Heparin-Gels mit einem Mono-substanzpräparat. Ergebnisse einer Doppelblind-cross-over-Studie. [Comparison of a salicylate heparin gel with a monosubstance preparation. Results of a double blind cross over study]. Munch Med Wochenschr. 1980, 122: 1231-1232.
36.
van Haselen RA, Fisher PA: A randomized controlled trial comparing topical piroxicam gel with a homeopathic gel in osteoarthritis of the knee. Rheumatology. 2000, 39: 714-719. 10.1093/rheumatology/39.7.714.CrossRefPubMed
37.
Vitali G: Sperimentazione clinica controllata sull'impiego topico dell'acido 2-(3-benzoil-fenil) proprionico a tre diverse concentrazioni. [Controlled clinical experiment with the topical use of 2-(3-benzoyl-phenyl) propionic acid at 3 different concentrations]. Clin Ter. 1980, 94: 257-273.PubMed
38.
Zacher J, Burger KJ, Farber L, Grave M, Abberger H, Bertsch K: Topical diclofenac versus oral ibuprofen: A double blind, randomized clinical trial to demonstrate efficacy and tolerability in patients with activated osteoarthritis of the finger joints (Heberden and/or Bouchard arthritis). Aktuelle Rheumatologie. 2001, 26: 7-14. 10.1055/s-2001-11369.CrossRef
39.
McCleane G: The addition of piroxicam to topically applied glyceryl trinitrate enhances its analgesic effect in musculoskeletal pain: A randomised, double-blind, placebo-controlled study. Pain Clinic. 2000, 12: 113-116. 10.1163/156856900750229861.CrossRef
40.
Ottillinger B, Gomor B, Michel BA, Pavelka K, Beck W, Elsasser U: Efficacy and safety of eltenac gel in the treatment of knee osteoarthritis. Osteoarthritis Cartilage. 2001, 9: 273-280. 10.1053/joca.2000.0385.CrossRefPubMed
41.
Sandelin J, Harilainen A, Crone H, Hamberg P, Forsskahl B, Tamelander G: Local NSAID gel (eltenac) in the treatment of osteoarthritis of the knee. A double blind study comparing eltenac with oral diclofenac and placebo gel. Scand J Rheumatol. 1997, 26: 287-292.CrossRefPubMed
42.
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
43.
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
44.
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
45.
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
46.
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
47.
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
48.
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
49.
Mason L, Moore RA, Edwards JE, McQuay HJ, Derry S, Wiffen PJ: Systematic review of topical rubefacients containing salicylates for the treatment of acute and chronic pain. BMJ. 2004, 238: 995-998. 10.1136/bmj.38040.607141.EE.CrossRef
50.
Mason L, Moore RA, Derry S, Edwards JE, McQuay HJ: Systematic review of topical capsaicin for the treatment of chronic pain. BMJ. 2004, 238: 991-994. 10.1136/bmj.38042.506748.EE.CrossRef
51.
Metadata
Title
Topical NSAIDs for chronic musculoskeletal pain: systematic review and 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 Musculoskeletal Disorders / Issue 1/2004
Electronic ISSN: 1471-2474
DOI
https://doi.org/10.1186/1471-2474-5-28

Other articles of this Issue 1/2004

BMC Musculoskeletal Disorders 1/2004 Go to the issue

Research article

Nodular osteochondrogenic activity in soft tissue surrounding osteoma in neurogenic para osteo-arthropathy: morphological and immunohistochemical study

Research article

The osteoporosis care gap in Canada

Research article

The effect of short-duration sub-maximal cycling on balance in single-limb stance in patients with anterior cruciate ligament injury: a cross-sectional study

Study protocol

The Knee Clinical Assessment Study – CAS(K). A prospective study of knee pain and knee osteoarthritis in the general population

Research article

Magnetic resonance imaging of anterior cruciate ligament rupture

Study protocol

The North Staffordshire Osteoarthritis Project – NorStOP: Prospective, 3-year study of the epidemiology and management of clinical osteoarthritis in a general population of older adults