The new finding promises to change current treatment of Crohn's disease, said study leader Dr William J. Sandborn, vice chair of gastroenterology and haepatology at the Mayo Clinic in Rochester, Minn. The results were reported in the New England Journal of Medicine.
Doctors now start treatment of Crohn's disease with steroids, Sandborn said. If the steroids do not provide relief from the abdominal pain, nausea, fever, weight loss, diarrhoea and other symptoms of the condition, the next step is to use azathioprine, which reduces immune system activity broadly. Only if that fails will they try biologics, newer treatments that include monoclonal antibodies such as infliximab (Remicade). These drugs target a specific part of the immune system.
The trial showed that the azathioprine-alone step should be skipped. "This study suggests that the therapy that follows steroids should include a biologic," Sandborn added.
Therapy with both azathioprine and infliximab appears to be the treatment of choice if steroids are not effective, Sandborn said.
"What this trial shows is that the most effective strategy is combination therapy," he said.
The results will alter treatment of Crohn's disease to some extent, said Dr. Jeffrey A. Katz, a spokesman for the Crohn's and Colitis Foundation of America, but by and large "it really does confirm what other studies suggest and what is clinically apparent, that combination therapy is better than treatment with azathioprine alone."
"It will push me in the direction of using combination therapy a bit more than I have been," said Katz, an associate professor of medicine at Case Western University School of Medicine in Cleveland.
The international trial included 508 people with Crohn's disease who had never been treated with immunosuppressive drugs. One-third were given infliximab alone, one-third received only azathioprine and one-third were treated with both. The trial was funded by Centocor Ortho Biotech, which markets infliximab, and Schering-Plough.
After 26 weeks, 56.8% of those getting combination therapy had complete remission of symptoms, compared to 44.4% of those getting only infliximab and 30% of those getting only azathioprine.
The most worrisome problem with drugs that repress immune system activity is a severe infection. That problem occurred in 3.9% of the people who used combination therapy, 4.9% of those in the infliximab group and 5.6% of those in the azathioprine group, a difference that is not statistically significant, Sandborn said.
And because the combination therapy is more effective, it helps prevent infections that result from ulceration of the intestinal wall caused by Crohn's disease, he added.
Safety issue still a concern
Fear of side effects such as serious infections has held back use of the combination therapy, Katz said.
And while the study "answers our questions in a select group of patients," it does not fully resolve the safety issue, said Dr. Simon Lichtiger, an associate professor of gastroenterology at Mount Sinai Medical Centre in New York City.
"The safety data aren't fully known and won't be known for a year," Lichtiger said. "It's not clear yet whether the advantages of the therapy exceed the possibility of long-term toxicity."
Crohn's disease is one of the two major forms of inflammatory bowel disease, whose underlying cause remains unclear. The other form is ulcerative colitis. An estimated 1 million Americans suffer from inflammatory bowel disease.
A similar study is underway in people with ulcerative colitis, Sandborn said. Results will not be available "for as much as a year or two," he noted. - (HealthDay News, April 2010)