Celebrex for the treatment of Ulcerative Colitis - Not a good idea

Stephen Holland, M.D.

A reader of the IBDList asked recently if a new antiinflammatory, Celebrex,would be useful in the treatment of Ulcerative Colitis.  The analogyof sulfasalazine, another drug with a salicylate component was offeredas a rational to try it.

Crohn's and UC are different from arthritis.  Some experience fromthe past is interesting in this regard.  A chemical in the body calledarachidonic acid is converted by a series of enzymes into several chemicalsthat are part of the signaling system for inflammation. Two class of chemicals,prostaglandins and another, leukotrienes, are of particular interest inIBD.  It turns out that prostaglandins are blocked by drugs like aspirin,Motrin, Nuprin, and other similar drugs.  However, the mesalaminedrugs, sulfasalazine, Asacol, Pentasa, and others, block leukotrienes.

Clinical experience has shown that Motrin and its cousins can actuallymake UC and Crohn's worse and cause flares, while mesalamine is beneficial. This clinical observation shows that leukotrienes are an important causeof inflammation in IBD, and prostaglandins are protective.

A new development in arthritis research is that prostaglandins are madeby two enzymes, cyclooxygenase-1 and cyclooxygenase-2 (COX-1 and COX-2). It has been found that prostaglandins made by COX-1 protect the stomachfrom injury, while COX-2 products are important in arthritis inflammation. A new drug on the market, Celebrex, (a.k.a. celecoxib) blocks COX-2 butnot COX-1.  It was predicted that this drug would be effective inarthritis and cause less injury to the stomach.  Animal studies andhuman studies have borne this out.

The natural question for IBD researchers - could a COX-2 inhibitor bebeneficial in IBD.

To evaluate that question and not put patients at risk, Brian Reuterat the University of Calgary in Alberta, Canada, gave the drug L745337( a drug similar to celecoxib ) to rats which had colitis induced by anenema of TNBS.  (This is a standard animal model of colitis). The results of the experiment were that the colitis was much worse in therats given the COX-2 inhibitor.  In fact, it was even worse than givingNaprosyn to the rats, which was also done in the experiment.  Additionally,giving etodolac, an NSAID which turns out to be somewhat more specificfor COX-2 than the run of the mill NSAID, was almost as bad as the pureCOX-2 inhibitor L745337.

These results lead me to recommend against giving Celebrex to anyonewith IBD.  It is interesting that the more selective the drug wasfor COX-2, the worse the rats did.  Certainly, there are other modelsof IBD, and it is possible that human UC or Crohn's will act differentlyat times than the animal models. However, I'd much rather see the animalstudies before trying the drug in people.  This is also a good exampleof how animal studies are beneficial.

Stephen Holland, M.D.

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