Science Editor

Why some people's gut immune reactions can spin out of control, leading to inflammatory bowel disease - which can take the form of either Crohn's disease or ulcerative colitis - is still largely unclear. But research presented at the Digestive Disease Week conference in New Orleans this week showed that that one risk factor for Crohn's, though not ulcerative colitis, is chronic aspirin use.

The study, presenting author Andrew Park, of the University of East Anglia, told reporters at a press conference, came from a prospective epidemiological study that looked at "many risk factors," with aspirin use just one of them.

Park and his colleagues found that people who took aspirin regularly for at least one year were nearly five times more likely to be diagnosed with Crohn's disease than those who did not, though his team did not ask how much aspirin the study subjects were taking and so has "no information on the absolute dose" that led to the increased risk.

In an interesting twist, smokers - though smoking is itself a risk factor for developing Crohn's - were protected from aspirin's effects. The researchers believe that in this particular case, the blood-thickening effects of smoking and the blood thinning effects of aspirin may cancel each other.

For those who don't feel smoking is a good risk-benefit tradeoff, ChemoCentryx presented Phase II/III PROTECT-1 trial data of its chemokine receptor antagonist Traficet-EN in maintaining remission of Crohn's disease over 36 weeks.

The PROTECT trial had previously shown that the drug reduced the severity of Crohn's disease in a 12-week induction study.

Following the induction study, patients who responded to Traficet-EN were randomized again to examine the drug's efficacy in maintaining remission. Patients who continued to receive the drug maintained a remission rate at about 50 percent, whereas the remission rate in those who were switched to placebo declined to about 30 percent. The difference between the two groups was statistically significant.

Petrus Bekker, ChemoCentryx senior vice president of medical affairs, speaking at a press conference told reporters that based on the results, ChemoCentryx intends to "facilitate as best we can, getting this compound into the hand of patients" as soon as possible. But he also noted that the ultimate decisions on the compound now rest with partner GlaxoSmithKline plc. GSK plans to initiate an additional trial with the compound later this year.

Researchers from Duke University also provided another update of the Phase II PROVE trial for Vertex Pharmaceuticals Inc's protease inhibitor telaprevir. Data from the study was presented "in a very similar format" at the European Association for the Study of the Liver Meeting in Vienna in April, said Andrew J. Muir, of Duke. Those results showed that many patients who did not achieve a so-called sustained virologic response, or SVR - that is, no viral RNA is detectable for at least six months after treatment - with the standard treatment of pegylated interferon alfa-2A and ribavirin could achieve such an SVR when telaprevir was added to the mix. (See BioWorld Today, April 16, 2010.)

Researchers also presented a retrospective analysis of about 450 patients that looked at the sustained virologic response specifically in difficult-to-treat patient populations including patients with a high viral load, cirrhosis, older or obese patients, or African Americans. Those difficult-to-treat patients, too, appeared to have improved response rates on telaprevir, although the finding was based on small group sizes and post-hoc analysis.

Study lead and director of GI/hepatology research at Duke University, Muir nevertheless termed the results "very encouraging." In fact, the hope that telaprevir may be available by 2011 if studies continue to go well is apparently leading some doctors to hold off with other treatments, which, Muir said, is "making me a little nervous."

Not every patient, he stressed, has the time to wait for experimental treatments. And if telaprevir does come on the market by 2011, Muir and panel moderator Philip Schoenfeld both noted the importance of investing in education for medical providers, and wristwatches for patients, to drive home the critical importance of sticking to the strict timing of telaprevir for avoiding resistance.

Otherwise, Schoenfeld noted, providers and patients risk repeating the mistake that was made when highly active antiretroviral treatment, or HAART, first became available for HIV: Not sticking carefully to the complicated timing of HAART drugs resulted, in many cases, in the rapid development of resistance.

Even where resistance does not develop, "every round of [HCV] therapy carries significant side effects with it," Muir said. "So if we do it, we should do it well."

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