To the Editors:

We would like to thank Dr. Rothschild for his comments pertaining to the ACR White Paper on the use of NSAIDs. The goal of the White Paper was to put forth recommendations for rheumatologists on the use of nonselective NSAIDs and selective COX-2 inhibitors. Clinicians and researchers with expertise in these agents and drug safety were part of the writing group for these recommendations. We summarized the currently available data and then offered a clinically-relevant set of recommendations on the use of NSAIDs. This document was the product of an extensive literature review and a vibrant dialogue among the writing group.

Dr. Rothschild takes issue with the recommendation that a patient taking aspirin for cardioprotection should avoid NSAIDs, suggesting that concomitant use of aspirin with celecoxib was not associated with an increase in GI risk. The subgroup analysis of aspirin users in the Celecoxib Long-Term Arthritis Safety Study found that combining aspirin with celecoxib was no safer than combining aspirin with a nonselective NSAID. In addition, several epidemiologic studies and randomized trials support our recommendation that combining aspirin with an NSAID is associated with elevations in GI risk (1, 2).

We agree with Dr. Rothschild in several important areas. First, misoprostol is a proven alternative to improve the GI safety of nonselective NSAIDs. Second, different dosing regimens of celecoxib (i.e., low versus high dose and daily versus twice daily) may be associated with different levels of cardiovascular risk. This has been suggested by several articles, but larger studies will be necessary to confirm these findings (3, 4). Finally, we agree with Dr. Rothschild that the benefit/risk ratio associated with nonselective NSAIDs and selective COX-2 inhibitors is unclear. Practicing rheumatologists have all observed many patients who use these agents, achieving great benefits without harm. Several recent studies have attempted to address whether there are subgroups of patients in whom these agents are more or less risky (4, 5). However, this is an important area for future work.

We would like to emphasize that the goal of the White Paper is not to serve as a rigid guideline for the treating clinician. The ACR commissioned this as a White Paper and not as a guideline because there is not “grade A” evidence for many important prescribing issues with NSAIDs. This White Paper was not written with medicolegal intentions. However, physicians need to make decisions based on the best available evidence, and sometimes the best available evidence is an expert-driven synthesis of the literature, such as the White Paper.

  • 1
    Silverstein FE, Faich G, Goldstein JL, Simon LS, Pincus T, Whelton A, et al. Gastrointestinal toxicity with celecoxib vs nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis: the CLASS study. A randomized controlled trial. JAMA 2000; 284: 124755.
  • 2
    Lanas A, Garcia-Rodriguez LA, Arroyo MT, Gomollon F, Feu F, Gonzalez-Perez A, et al, and the Asociación Española de Gastroenterología. Risk of upper gastrointestinal ulcer bleeding associated with selective cyclo-oxygenase-2 inhibitors, traditional non-aspirin non-steroidal anti-inflammatory drugs, aspirin and combinations. Gut 2006; 55: 17318.
  • 3
    Solomon SD, Pfeffer MA, McMurray JJ, Fowler R, Finn P, Levin B, et al, and the APC and PreSAP Trial Investigators. Effect of celecoxib on cardiovascular events and blood pressure in two trials for the prevention of colorectal adenomas. Circulation 2006; 114: 102835.
  • 4
    Solomon SD, Wittes J, Finn PV, Fowler R, Viner J, Bertagnolli MM, et al, for the Cross Trial Safety Assessment Group. Cardiovascular risk of celecoxib in 6 randomized placebo-controlled trials: the Cross Trial Safety Analysis. Circulation 2008; 117: 210413.
  • 5
    Solomon DH, Glynn RJ, Rothman KJ, Schneeweiss S, Setoguchi S, Mogun H, et al. Subgroup analyses to determine cardiovascular risk associated with nonsteroidal antiinflammatory drugs and coxibs in specific patient groups. Arthritis Rheum 2008; 59: 1097104.

Sonali P. Desai MD*, Daniel H. Solomon MD, MPH*, Steven B. Abramson MD†, Lenore Buckley MD, MPH‡, Leslie J. Crofford MD§, John J. Cush MD¶, Daniel J. Lovell MD, MPH**, Kenneth G. Saag MD, MSc††, * Brigham & Women's Hospital, Boston, MA, † New York University Hospital for Joint Diseases, New York, NY, ‡ Virginia Commonwealth University, Richmond, VA, § University of Kentucky, Lexington, KY, ¶ Baylor University Medical Center, Dallas, TX, ** Children's Hospital Medical Center, Cincinnati, OH, †† University of Alabama, Birmingham, Birmingham, AL.