SELECTED ARTICLES FROM THE RECENT LITERATURE 2003

12/29/03

COX-2 inhibitors and aspirin-exacerbated respiratory disease

Summary
There has been a marked increase in the use of COX-2 inhibitors such as celecoxib (Celebrex) and rofecoxib (Vioxx) because of a lower incidence of adverse G-I side effects than seen with NSAID use (Med J Austral 2002;176:328-31). However, as reviewed by Crofford of the Univ of Michigan in Ann Arbor, MI, concerns have been raised about the tolerance of COX-2 inhibitor agents by individuals with aspirin-exacerbated respiratory disease (AERD), including those with so-called "triad asthma". Individuals with AERD (about 10% of all chronic adult asthmatics) often have worsening of their respiratory symptoms triggered by ingestion of NSAID agents. This triggering has been postulated to be due to inhibition by NSAID of the formation of protective prostaglandins from arachidonic acid while skewing conversion of arachidonic acid to the synthesis of pro-inflammatory cysteinyl leukotrienes. However, clinical data suggest that formation of such protective prostaglandins involve the COX-1 not the COX-2 pathways. Other studies have shown that COX-2 inhibitors do not cross-react with aspirin and do not cause respiratory worsening in patients with AERD.

Reference
Arthritis Res Ther 2003;5:25-7

Editor's Comments
The conclusions described above are similar to that expressed by the Scripps Clinic group, very active investigators in this area after carrying out appropriate challenge studies with rofecoxib (J Allergy Clin Immunol 2001;108:47-51). Others have found that celecoxib is safe in AERD patients (J Invest Allergol Clin Immunol 2003;13:20-25; J Allergy Clin Immunol 2003; 111:116-21). In the last noted study, no evidence of increased leukotriene formation was found following celecoxib challenge in these AERD patients. Thus, we can conclude with reasonable certainty that these selective COX-2 inhibitors are tolerated by AERD patients. Of note, a recent review found no evidence of an increased frequency of cardiovascular thrombotic events in patients taking COX-2 inhibitors (Am Heart J 2003;146:591-604).
 

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