The Editorial Executive Committee welcomes letters, which should be less than 250 words. Before a decision to publish is made, letters which refer to a published article may be sent to the author for a response. Any letter may be sent to an expert for comment. When letters are published, they are usually accompanied in the same issue by their responses or comments. The Committee screens out discourteous, inaccurate or libellous statements. The letters are sub-edited before publication. Authors are required to declare any conflicts of interest. The Committee's decision on publication is final.

Letter to the editor

Editor, – It was disappointing to read that there are still people questioning the gastrointestinal safety and cost-effectiveness of the COX-2 inhibitors (Aust Prescr 2004; 27:2-3). It is even more disappointing when this opinion is referenced to a single non-systematic, heterogenous review article (that is, evidence level 5), which misrepresents the body of evidence in two important ways.

The review claims that non-steroidal anti-inflammatory drugs (NSAIDs) have minimal benefit against which to compare their adverse events. This is based on a very selective use of analgesic data from the literature (which still showed a significant difference to placebo). An alternative view is that NSAIDs are the mainstay of therapy worldwide for the symptomatic relief of arthritis and occupy the first five top rankings for analgesics on the Oxford pain relief table because of their clinical benefits.1 This is backed by clinical trials where both COX-2 inhibitors and traditional NSAIDs showed statistically and clinically different efficacy to placebo in arthritis.2,3,4,5

The article by Wright also states that there is no evidence for reduced gastrointestinal damage from COX-2 inhibitors. He bases this opinion on a single flawed study (CLASS) that had a statistical power of about 45% (that is, less than a 50% chance of detecting any real differences).6 He neglects to mention the wealth of other data from adequately powered studies that show a significant difference in safety and tolerability between celecoxib and the non-specific NSAIDs.7, 8, 9, 10,11,12,13

If the COX-2 inhibitors did not represent a cost-effective treatment then they would not be listed on the Pharmaceutical Benefits Scheme. The Pharmaceutical Benefits Advisory Committee makes this decision based on evidence, not opinion.

Dr Simon McErlane
Medical Director
Pfizer Global Pharmaceuticals
Pfizer Australia


Associate Professor J. Lexchin, the author of the editorial, comments:

Dr McErlane dismisses the results of the CLASS study on celecoxib by claiming that it was underpowered to find significant benefits. CLASS was funded by Pharmacia, the company that marketed celecoxib, and the corresponding author was a Pharmacia employee. Pharmacia is now owned by Pfizer. If there was a problem with the design of CLASS then Dr McErlane should look to his own house.

He criticises the article by Dr Jim Wright for ignoring seven articles showing the gastrointestinal benefits of COX-2 inhibitors. However, one was a poster presentation that was otherwise unpublished and two were published either just before or after Dr Wright's piece and would have been unavailable to him.

Dr McErlane has misread Wright's article. Wright does not say that COX-2 drugs have minimal benefits; what he does say is that the benefits need to be seen in the context of serious adverse events from these drugs. Serious adverse events include not only gastrointestinal problems but other adverse events. Wright combines all serious adverse events as reported in the CLASS study for celecoxib and for other NSAIDs and shows that there is no statistical difference in serious adverse events between celecoxib and the other NSAIDs. In other words, whatever reduction in gastrointestinal harms celecoxib produced was offset by a higher incidence of other serious adverse events.

Dr McErlane's letter provides a good lesson in why doctors should not rely solely on what companies have to say about their products.

Author's comments

Associate Professor J. Lexchin, the author of the editorial, comments:

Dr McErlane dismisses the results of the CLASS study on celecoxib by claiming that it was underpowered to find significant benefits. CLASS was funded by Pharmacia, the company that marketed celecoxib, and the corresponding author was a Pharmacia employee. Pharmacia is now owned by Pfizer. If there was a problem with the design of CLASS then Dr McErlane should look to his own house.

He criticises the article by Dr Jim Wright for ignoring seven articles showing the gastrointestinal benefits of COX-2 inhibitors. However, one was a poster presentation that was otherwise unpublished and two were published either just before or after Dr Wright's piece and would have been unavailable to him.

Dr McErlane has misread Wright's article. Wright does not say that COX-2 drugs have minimal benefits; what he does say is that the benefits need to be seen in the context of serious adverse events from these drugs. Serious adverse events include not only gastrointestinal problems but other adverse events. Wright combines all serious adverse events as reported in the CLASS study for celecoxib and for other NSAIDs and shows that there is no statistical difference in serious adverse events between celecoxib and the other NSAIDs. In other words, whatever reduction in gastrointestinal harms celecoxib produced was offset by a higher incidence of other serious adverse events.

Dr McErlane's letter provides a good lesson in why doctors should not rely solely on what companies have to say about their products.

References

  1. Oxford league table of analgesics in acute pain. http://www.jr2.ox.ac.uk/bandolier/booth/painpag/Acutrev/Analgesics/Leagtab.html [cited 2004 May 14]
  2. McKenna F, Borenstein D, Wendt H, Wallemark C, Lefkowith JB, Geis GS. Celecoxib versus diclofenac in the management of osteoarthritis of the knee. Scand J Rheumatol 2001;30:11-8.
  3. Gibofsky A, Williams GW, McKenna F, Fort JG. Comparing the efficacy of cyclooxygenase 2-specific inhibitors in treating osteoarthritis: appropriate trial design considerations and results of a randomized, placebo-controlled trial. Arthritis Rheum 2003;48:3102-11.
  4. Simon LS, Weaver AL, Graham DY, Kivitz AJ, Lipsky PE, Hubbard RC, et al. Anti-inflammatory and upper gastrointestinal effects of celecoxib in rheumatoid arthritis: a randomized controlled trial. JAMA 1999;282:1921-8.
  5. Weisman MH. Double-blind randomized trial of diclofenac sodium versus placebo in patients with rheumatoid arthritis. Clin Ther 1986;8:427-38.
  6. Wright JM. The double-edged sword of COX-2 selective NSAIDs. CMAJ 2002;167:1131-7.
  7. Singh G, Goldstein J, Bensen W, Agrawal N, Eisen G, Fort J, et al. SUCCESS-1 in osteoarthritis (OA) trial: celecoxib significantly reduces the risk of serious upper GI complications compared to NSAIDs while providing similar efficacy in 13,274 randomized patients [poster presented at EULAR; 2001 June 13-16; Prague].
  8. Goldstein JL, Silverstein FE, Agrawal NM, Hubbard RC, Kaiser J, Maurath CJ, et al. Reduced risk of upper gastrointestinal ulcer complications with celecoxib, a novel COX-2 inhibitor. Am J Gastroenterol 2000;95: 1681-90.
  9. Mamdani M, Rochon PA, Juurlink DN, Kopp A, Anderson GM, Naglie G, et al. Observational study of upper gastrointestinal haemorrhage in elderly patients given selective cyclo-oxygenase-2 inhibitors or conventional non-steroidal anti-inflammatory drugs. Br Med J 2002;325:624.
  10. Chan FK, Hung LC, Suen BY, Wu JC, Lee KC, Leung VK, et al. Celecoxib versus diclofenac and omeprazole in reducing the risk of recurrent ulcer bleeding in patients with arthritis. N Engl J Med 2002;347:2104-10.
  11. Bensen WG, Zhao SZ, B, Zabinski RA, Makuch RW, Maurath CJ, et al. Upper gastrointestinal tolerability of celecoxib, a COX-2 specific inhibitor, compared to naproxen and placebo. J Rheumatol 2000;27:1876-83.
  12. McKenna F, Arguelles L, Burke T, Lefkowith J, Geis GS. Upper gastrointestinal tolerability of celecoxib compared with diclofenac in the treatment of osteoarthritis and rheumatoid arthritis. Clin Exp Rheumatol 2002;20:35-43.
  13. Goldstein JL, Eisen GM, B, Pena BM, Lefkowith J, Geis GS. Dyspepsia tolerability from the patients' perspective: a comparison of celecoxib with diclofenac. Aliment Pharmacol Ther 2002;16:819-27.