2008年8月14日Efficacy of Topical NSAIDs in the Treatment of Osteoarthritis:A Meta-analysis of Randomized Controlled Trials_Chinese Journal of Evidence-Based Medicine

Authors：

Lin JinYin ¹ , Zhang WeiYa ² , Adrian Jones ³ , Michael Doherty ²

1.Department of Rheumatology; The People’s Hospital of Guangxi Zhuang Autonomous Region; Nanning; 530021; China2.Academic Rheumatology; Clinic Science Building; City Hospital; Nottingham NG51PB; UK3.Department of Rheumatology;

Corresponding author：

Keywords：

Treatment of osteoarthritis; Topical non-steroidal anti-inflammatory drug; Meta-analysis; Randomized controlled trial

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Objective 　To assess the efficacy of topical non-steroidal anti-inflammatory drugs （NSAIDs） in the treatment of osteoarthritis （OA）.
Methods　MEDLINE, EMBASE, Scientific Citation Index, CINAHL, The Cochrane Library, CBMdisc and abstracts from conference were searched from 1966 to March 30, 2005. Randomized controlled trials （R.CT） comparing topical non-steroidal anti-inflammatory drug （NSAIDs） with placebo or oral NSAIDs in OA were induded. Effect size （ES） was calculated for pain, function and stiffness. Relative risk （RR） was calculated for dichotomous data such as clinical response rate and adverse effect rate. Number needed to treat to obtain the clinical response was estimated. The quality of trials was assessed and sensitivity analyses were undertaken.
Results 　Topical NSAIDs were superior to placebo in relieving pain due to osteoarthritis only in the first 2 weeks of treatment; ES （95% CI） were 0.41 （0. 16 to 0.66） and 0.40 （0.15 to 0.65） at week 1 and 2 respectively. However, the effects were short-lived and no benefit was observed over placebo at the third and fourth week. A similar pattern was observed with function, stiflhess and clinical response RR and number needed to treat. Topical NSAIDs were inferior to oral NSAIDs at week 1, and associated with more local side effects such as rash, itch or burning （RR 5.29, 95% CI 1.14 to 24. 51 ）.
Conclusions 　Only very shortterm （less than 4 weeks） RCTs have assessed topical NSAID efficacy in OA ; after 2 weeks no efficacy above placebo has been obsevrved. There are no trial data to support the long-term use of topical NSAIDs in osteoarthritis.

Citation： Lin JinYin,Zhang WeiYa,Adrian Jones,Michael Doherty. 2008年8月14日Efficacy of Topical NSAIDs in the Treatment of Osteoarthritis:A Meta-analysis of Randomized Controlled Trials. Chinese Journal of Evidence-Based Medicine, 2005, 05(9): 667-674. doi: Copy

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4.	Moore RA, Tramer MR, Carroll D, Wiffen PJ, McQuay HJ. Quantitative systematic review of topical applied non-steroidal anti-inflammatory drugs[J]. BMJ,1998;316(7137): 333-338.
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8.	Whitehead A, Whitehead J. A general parametric approach to the meta-analysis of randomised clinical trials[J]. Stat Med, 1991;10(11): 1665-1677.
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22.	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)[J]. Aktuel Rheumatol, 2001;26(1): 7-14.
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24.	Scott DL. Guidelines for the diagnosis, investigation and management of osteoarthritis of the hip and knee. Report of the Joint Working Group of the British Society for Rheumatology and the Research Unit of the Royal College of Physician[J]. J R Coll Physicians Lond, 1993;27(4): 391-396.
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1. Yelin E. The earnings, income, and assets of persons aged 51-61 with and without musculoskeletal conditions[J]. J Rheumatol,1997;24(10): 2024-2030.
2. Wynne HA, Campell M. Pharmacoeconomics of nonsteroidal anti-inflammatory drugs (NSAIDs) [J]. Pharmacoeconomics, 1994;3(2): 107-123.
3. Anon. Trolamine salycylate cream in osteoarthritis of the knee[J]. JAMA, 1982;247(9): 1311-1313.
4. Moore RA, Tramer MR, Carroll D, Wiffen PJ, McQuay HJ. Quantitative systematic review of topical applied non-steroidal anti-inflammatory drugs[J]. BMJ,1998;316(7137): 333-338.
5. Cook RJ, Sackett DL. The number needed to treat: a clinically useful measure of treatment effect[J]. BMJ,1995; 310(6977):452-454.
6. Whitehead A, Whitehead J. A general parametric approach to the meta-analysis of randomised clinical trials[J]. Stat Med, 1991; 10(11):1665-1677.
7. Cook RJ, Sackett DL. The number needed to treat: a clinically useful measure of treatment effect[J]. BMJ, 1995;310(6977): 452-454.
8. Whitehead A, Whitehead J. A general parametric approach to the meta-analysis of randomised clinical trials[J]. Stat Med, 1991;10(11): 1665-1677.
9. Egger M, Smith JD, Schneider M, Minder C. Bias in meta-analysis detected by a simple graphical test[J]. BMJ, 1997;315(9074): 629-634.
10. Algozzine GJ, Pharm D, Gerald H, Doering PL, Araujo OE, Akin KC. Trolamine salicylate cream in osteoarthritis of the knee[J]. JAMA, 1982;247(9): 1311-1313.
11. Bruhlmann P, Michel BA. Topical diclofenac patch in patients with knee osteoarthritis: a randomized, double-blind, controlled clinical trial[J]. Clin Exp Rheumatol,2003;21(2): 193-198.
12. Dreiser RL, Tisne-Camus M. DHEP plasters as a topical treatment of knee osteoarthritis-a double-blind placebo-controlled study[J]. Drugs Exp Clin Res, 1993;19(3): 117-123.
13. 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]. J Rheumatol,1999;26(12): 2659-2663.
14. Ottillinger B, Gomor B, Michel BA, Pavelka K, Beck W, Elsasser U. Efficacy and safety of eltenac gel in the treatment of knee osteoarthritis[J]. Osteoarthritis Cartilage, 2001;9(3): 272-280.
15. 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[J]. Int J Tiss React, 1995;17(4): 129-132.
16. Rothacher D, Difigilo C, Lee I. A clinical trial of topical 10% trolamine salicylate in osteoarthritis[J]. Curr Ther Res, 1994;55(5): 584-597.
17. Rothacker DQ, Lee I, Littlejohn III TW. Effectiveness of a single topical application of 10% trolamine salicylate cream in the symptomatic treatment of osteoarthritis[J]. J Clin Rheumatol,1998;4(1): 6-12.
18. 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[J]. Drugs Exp Clin Res, 2001;27(5/6): 209-221.
19. Shackel NA, Day RO, Kellet B, Books PM. Copper-salicylate gel for pain relief in osteoarthritis: a randomized controlled trial[J]. Med J Aust, 1997;167(3): 134-136.
20. 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[J]. Scand J Rheumatol, 1997;26(4): 287-292.
21. Dickson D J. A double-blind evaluation of topical piroxicam gel with oral ibuprofen in osteoarthritis of the knee[J]. Curr Ther Res, 1991;49(2): 199-207.
22. 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)[J]. Aktuel Rheumatol, 2001;26(1): 7-14.
23. Walker-Bone K, Javaid K, Arden N, Cooper C. Medical management of osteoarthritis[J]. BMJ,2000;321(7266): 936-940.
24. Scott DL. Guidelines for the diagnosis, investigation and management of osteoarthritis of the hip and knee. Report of the Joint Working Group of the British Society for Rheumatology and the Research Unit of the Royal College of Physician[J]. J R Coll Physicians Lond, 1993;27(4): 391-396.
25. Jordan KM, Arden NK, Doherty M, Bannwarth B, Bijlsma JW, Dieppe P, Gunther K, Hauselmann H, Herrero-Beaumont G, Kaklamanis P, Lohmander S, Lecb B, Lequesne M, Mazieres B, Martin-Mola E, Pavelka K, Pendleton A, Punzi L, Serni U, Swoboda B, Verbruggen G, Zimmerman-Gorska I, Dougados M, Standing Committee for International Clinical Studies Including Therepeutic Trials ESCISIT. EULAR recommendations 2003: an evidence based approach to the management of knee osteoarthritis: report of a Task Force of the Standing Committee for International Clinical Studies Including Therapeutic Trials (ESCISIT)[J]. Ann Rheum Dis, 2003;62(12): 1145-1155.
26. American College of Rheumatology Subcommittee on Osteoarthritis Guidelines. Recommendations for the medical management of osteoarthritis of the hip and knee[J]. Arthritis Rheum, 2000; 43(9):1905-1915.

Chinese Journal of Evidence-Based Medicine

2008年8月14日Efficacy of Topical NSAIDs in the Treatment of Osteoarthritis:A Meta-analysis of Randomized Controlled Trials

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