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Rapid Responses: Rapid Responses published:
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Practical Usefulness of Single Patient Based Medicine.
- Sergio Stagnaro (7 August 2004)
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Potential benefits of topical NSAIDs
- Pamela L Cross, Enid Hennessey, Ken Whyte, Martin Underwood, on behalf of the TOIB Study team (17 August 2004)
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Not always harmless
- Christopher Anton (18 August 2004)
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Efficacy of topical NSAIDs in osteoarthritis, a meta-analysis: There are longer trials that show efficacy.
- J. Zev Shainhouse (19 August 2004)
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studies support topical nsaid efficacy in on long term osteoarthritis treatment
- sanford h. roth (2 September 2004)
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Sergio Stagnaro, Specialist in Blood, Gastrointestinal, and Metabolic Diseases. Researcher in Biophysical Semeiotics. Via Erasmo Piaggio 23/8 16037 Riva Trigoso (Genova) Italy
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Sirs, as regards assessing the efficacy of topical non-steroidal anti- inflammatory drugs (NSAIDs) in the treatment of osteoarthritis, one my agree “generally” with paper’s authors who conclude that “Randomised controlled trials of short duration only (less than four weeks) have assessed the efficacy of topical NSAIDs in osteoarthritis. After two weeks there was no evidence of efficacy superior to placebo. No trial data support the long term use of topical NSAIDs in osteoarthritis”. However, in the day-to-day practice, doctor treats a single patient, who respondes to treatment often in an unpredictable way, very different from that observed in “large” tials (2, 3). Biophysical-Semeiotic Constitutions account for the reason of such as behaviour (3, 4)(See HONCode website 233736, www.semeioticabiofisica.it). We must, therefore, be able to apply EBM beside to Single Patient Based Medicine (4) (See above-cited website) in both research and therapy: for example, “What does it means to investigate cancerogenic properties of whatever drugs in individuals not involved by oncological terrain?”. 1) Lin J., Zhang W., et al. Efficacy of topical non-steroidal anti- inflammatory drugs in the treatment of osteoarthritis: meta-analysis of randomised controlled trials BMJ 2004;329:324 (7 August), doi:10.1136/bmj.38159.639028.7C (published 30 July 2004) 2) Stagnaro S. “Single Patient Based Medicine” versus EBM. (16 May 2003) http://bmj.com/cgi/eletters/326/7398/1048#32299 3) Stagnaro-Neri Marina, Stagnaro Sergio. Introduzione alla Semeiotica Biofisica. Il Terreno oncologico”. Travel Factory SRL., Roma, 2004. http://www.travelfactory.it/semeiotica_biofisica.htm 4) Stagnaro-Neri Marina, Stagnaro Sergio. Le Costituzioni Semeiotico- Biofisiche. Single Patient Based Medicine. Travel Factory SRL., Roma, 2004 (in press). Competing interests: None declared |
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Pamela L Cross, Clinical Research Fellow Centre for General Practice and Primary Care, Queen Mary's, Mile End Road, London E1 4NS, Enid Hennessey, Ken Whyte, Martin Underwood, on behalf of the TOIB Study team
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We were interested in Lin et al’s suggestion that current advice to use topical non-steroidal anti-inflammatory drugs (NSAIDs) to treat osteoarthritis might need revising(1). They conclude that, when compared to placebo, topical NSAIDs have only short term benefit. Any benefit these preparations might have may, at least in part, be mediated through non-pharmacological factors. For example, the effect of rubbing a painful area, or the expectation of benefit from rubbing medication directly into the affected area, may have a beneficial effect. The continued popularity of rubefacients with no active ingredient and, in one study, the use of topical motor oil and WD-40 as treatments for painful joints indicates the potential importance of these non-pharmacological factors(2). The other part of the picture is the incidence of adverse events. The high incidence of adverse events from oral NSAIDs and cycloxygenase-2 inhibitors are well known. Oral NSAIDs have also only been shown to have a short term beneficial effect for those with osteoarthritis(3). One might expect topical NSAIDs to have fewer side effects than their oral equivalent. Thus even if topical NSAIDs have little additional pharmacological effect when compared to placebo, if they are used instead of oral preparations they might produce an overall health benefit. It is perhaps premature to write topical NSAIDs out of treatment recommendations for osteoarthritis until we have more data on their effectiveness and safety compared to oral preparations. 1. Lin J, Zhang W, Jones A, Doherty M. Efficacy of topical non- steroidal anti-inflammatory drugs in the treatment of osteoarthritis: meta -analysis of randomised controlled trials. BMJ 2004. 2. Arcury TA, Gesler WM, Cook HL. Meaning in the use of unconventional arthritis therapies. Am.J.Health Promot. 1999;14:7-15. 3. Scott DC, Smith C, Lohmander S, Chard J. Osteoarthritis. Clinical Evidence 2002;8:1212-37. Competing interests: MU is the chief investigator, KW trial manager, EH trial statistician, and PC trial clinician, on an NHS HTA funded study comparing the long term risk and benefits of topical and oral ibuprofen for knee pain in older people. MU has received fees for speaking from Menarini Pharmaceuticals, the manufacturers of Dexketoprofen and Ketoprofen, and Pfizer, the manufacturers of Celecoxib and Valdecoxib. |
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Christopher Anton, Administrative Co-ordinator West Midlands Centre for Adverse Drug Reaction Reporting, Birmingham B18 7QH
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Dear Editor Topical NSAIDs may have fewer potentially serious adverse effects than oral preparations [1] but they are not immune. Topical NSAIDs have to be absorbed to exert their therapeutic effects, and so they can cause systemic adverse effects. They have been implicated in cases of renal failure,[2-4] gastrointestinal haemorrhage,[5] and asthma.[6] Prescribers should be vigilant to topical NSAIDs causing systemic ADRs and report suspected adverse reactions to drug regulatory agencies. 1. Lin J, Zhang W, Jones A, Doherty M. Efficacy of topical non- steroidal anti-inflammatory drugs in the treatment of osteoarthritis: meta -analysis of randomised controlled trials. BMJ 2004; 329: 324. 2. Krummel T, Dimitrov Y, Moulin B, Hannedouche T. Drug points: Acute renal failure induced by topical ketoprofen. BMJ 2000; 320: 93. 3. Evans JM, McGregor E, McMahon AD, et al. Non-steroidal anti- inflammatory drugs and hospitalization for acute renal failure. QJM 1995; 88: 551-7. 4. Fernando AH, Thomas S, Temple RM, Lee HA. Renal failure after topical use of NSAIDs. BMJ 1994; 308: 533. 5. Evans JM, McMahon AD, McGilchrist MM, et al. 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: 22-6. 6. Gaynes BI, Fiscella R. Topical nonsteroidal anti-inflammatory drugs for ophthalmic use: a safety review. Drug Saf. 2002; 25: 233-50. Competing interests: None declared |
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J. Zev Shainhouse, Medical Director Dimethaid Health Care Ltd., 1405 Denison St., Markham, ON, Canada, L3R 5V2
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Based on an updated literature review, Lin et al. (1) challenge the conclusion of an earlier meta-analysis (2) on the efficacy of topical non- steroidal anti-inflammatory drugs (NSAIDs) in treating osteoarthritis (OA). They disagree with Moore et al. (2) who judged that topicals were effective, based on 2-week data, and call for studies of at least 4 weeks duration to provide clinical relevance. The authors did not cite four randomised, double-blinded studies of knee OA, assessing efficacy according to the Western Ontario and McMaster Universities (WOMAC) OA Index and published in abstract form after presentation at major conferences. (3-6) These studies with diclofenac cutaneous solution 16 mg/ml (PENNSAID) include three placebo- and/or vehicle-controlled superiority trials (poster presentations) of 4, 6 and 12 weeks duration in 248, 216 and 326 patients. (3-5) They were designed specifically to overcome the limitations in size and duration identified by Lin et al. In all three studies, intent-to-treat analysis of the change from baseline to final in all efficacy variables—WOMAC pain, physical function and stiffness subscale scores, and patient global assessment—demonstrated the superiority of topical diclofenac. The fourth abstract (oral presentation) describes an adequately powered, 12-week equivalence trial in 622 patients comparing efficacy with the same drug, diclofenac, given topically or orally (similar to the ongoing Health Technology Assessment trial of ibuprofen in the UK). (6) After citing literature that defined a priori sets of equivalence ranges and using WOMAC subscales and a patient global assessment as outcome measures, statistical equivalence between this topical diclofenac solution (PENNSAID) and the maximum daily dose of oral diclofenac was demonstrated. The publication of full data from these abstracts will facilitate a more complete review of this subject and this new product. (7) 1. Lin J, Zhang W, Jones A, Doherty M. Efficacy of topical non- steroidal anti-inflammatory drugs in the treatment of osteoarthritis: meta -analysis of randomised controlled trials. BMJ, doi:10.1136/bmj.38159.639028.7C (published 30 July 2004). 2. Moore RA, Tramer MR, Carroll D, Wiffen PJ, McQuay HJ. Quantitative systematic review of topical applied non-steroidal anti-inflammatory drugs. BMJ 1998;316:333-8. 3. Bookman AAM, Shainhouse JZ, Williams K. A multicenter study of diclofenac topical lotion (PENNSAID®) in patients with osteoarthritis of the knee. Arthritis Rheum 1999; 42(9; Suppl):S142. 4. Baer P, Williams K, Markus G, Shainhouse JZ. A multi-centre, double-blinded, placebo-controlled, clinical trial of diclofenac topical lotion (PENNSAID®) in the treatment of the symptoms of primary osteoarthritis of the knee. Rheumatology Oxford 2001; 40 (Suppl 1):107. 5. Roth SH, Shainhouse JZ. A U.S., multi-center, placebo-controlled, double-blinded clinical trial of diclofenac topical solution (PENNSAID®) in the treatment of the symptoms of primary osteoarthritis of the knee. Ann Rheum Dis 2002; 61 (Suppl I):125. 6. Tugwell PS, Wells GA, Shainhouse JZ. A comparative trial of oral versus topical diclofenac in the treatment of osteoarthritis of the knee. Ann Rheum Dis 2003; 62 (Suppl I):73. 7. Bookman AAM, Williams KSA, Shainhouse JZ. Effect of a topical diclofenac solution for relieving symptoms of primary osteoarthritis of the knee: a randomized controlled trial. CMAJ 2004; 171:333-8. Competing interests: JZ is a paid employee of Dimethaid Health Care and has shares in the company. |
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sanford h. roth, M.D. 6831 no. 58th place,paradise valley,az 85253
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STUDIES SUPPORT TOPICAL NSAID EFFICACY IN LONG-TERM OSTEARTHRITIS TREATMENT Although the meta-analysis by Lin et al.1 supports efficacy of topical NSAIDs in OA, the authors conclude that the trials they reviewed provide insufficient evidence to warrant long-term use, beyond two-weeks. This is a serious matter because systemic NSAID toxicity has been identified as a major problem, especially among the elderly who make up the core OA treatment population.2,3 A proven alternative to systemic NSAIDs is urgently required. The use of topical NSAIDs, which except for local skin reactions are essentially free from serious toxicities, has been supported by other meta -analyses demonstrating efficacy as well as safety.4,5 I would also draw attention to published conference abstracts from the European League Against Rheumatism (EULAR 2002 and 2003), documenting two 3-month RCTs in relatively large populations of OA patients.6,7 While it is always desirable to have more RCT data, the reality is that widespread, long-term, experience using topical NSAIDs for localized joint problems is consistent with these more encouraging clinical trials. 1.Lin J, Zhang W, Jones A, Doherty M. Efficacy of topical non- steroidal, anti-inflammatory drugs in the treatment of osteoarthritis: meta-analysis of randomised controlled trials. BMJ, doi:10:1136/BMJ.38159.639028.7C 2.Roth S: Arthritis Therapy: A Better Time, A Better Day. Rheumatology (Oxford) 2001, 40:603-606. 3.Fries J, Williams C,Bloch D, Michel B: NSAID associated gastropathy: incidence and risk Factor models. Am J Med. 1991, 91:213-222, 4.Moore R, Tramer M, Carroll, Wiffen P, McQuay H: Quantitative systematic review of topically applied NSAIDs. BMJ. 1998, 316:333-338. 5.Mason L, Moore RA, Edwards JE, Derry S, McQuay HJ. Topical NSAIDs for chronic musculoskeletal pain: systematic review and meta-analysis. BMC doi:10.1186/1471-2474 -5-28. 6.Roth SH, Shainhouse JZ. A U.S., multi-center, placebo-controlled, double -blinded, clinical trial of diclofenac topical solution (Pennsaid) in the treatment of the symptoms of primary osteoarthritis of the knee. Ann Rheum Dis 2002;61(Suppl I):125. 7.Tugwell PS, Wells GA, Shainhouse JZ. A comparative trial of oral versus topical diclofenac in the treatment of osteoarthritis of the knee. Ann Rheum Dis 2003;62 (Suppl I):73. Competing interests: Dimethaid principal investigator and consultant.No financial interests. |
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