A reader of the IBDList asked recently if a new anti-inflammatory, Celebrex, would be useful in the treatment of Ulcerative Colitis. The analogy of sulfasalazine, another drug with a salicylate component was offered as a rational to try it.
Crohn’s and UC are different from arthritis. Some experience from the past is interesting in this regard. A chemical in the body called arachidonic acid is converted by a series of enzymes into several chemicals that 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 mesalamine drugs (sulfasalazine, Pentasa, and others) block leukotrienes.
Clinical experience has shown that Motrin and its cousins can actually make UC and Crohn’s worse and cause flares, while mesalamine is beneficial. This clinical observation shows that leukotrienes are an important cause of inflammation in IBD, and prostaglandins are protective.
A new development in arthritis research is that prostaglandins are made by two enzymes, cyclooxygenase-1 and cyclooxygenase-2 (COX-1 and COX-2). It has been found that prostaglandins made by COX-1 protect the stomach from injury, while COX-2 products are important in arthritis inflammation. A new drug on the market, Celebrex, (a.k.a. celecoxib) blocks COX-2 but not COX-1. It was predicted that this drug would be effective in arthritis and cause less injury to the stomach. Animal studies and human studies have borne this out.
The natural question for IBD researchers – could a COX-2 inhibitor be beneficial in IBD.
To evaluate that question and not put patients at risk, Brian Reuter at the University of Calgary in Alberta, Canada, gave the drug L745337( a drug similar to celecoxib ) to rats which had colitis induced by an enema of TNBS. (This is a standard animal model of colitis). The results of the experiment were that the colitis was much worse in the rats given the COX-2 inhibitor. In fact, it was even worse than giving Naprosyn to the rats, which was also done in the experiment. Additionally, giving etodolac, an NSAID which turns out to be somewhat more specific for COX-2 than the run of the mill NSAID, was almost as bad as the pure COX-2 inhibitor L745337.
These results lead me to recommend against giving Celebrex to anyone with IBD. It is interesting that the more selective the drug was for COX-2, the worse the rats did. Certainly, there are other models of IBD, and it is possible that human UC or Crohn’s will act differently at times than the animal models. However, I’d much rather see the animal studies before trying the drug in people. This is also a good exampleof how animal studies are beneficial.
