Stubborn ulcerative colitis responds to arthritis drug, review finds

In good news for patients with stubborn cases of ulcerative colitis, a serious intestinal disorder, a new research review suggests that the drug infliximab can be a useful alternative if other treatments don't work.

The drug is currently used to treat rheumatoid arthritis and Crohn's disease.

"For people with active ulcerative colitis who do not respond to corticosteroids or immunosuppressive agents, infliximab is effective in inducing clinical remission, inducing clinical response, promoting mucosal healing and reducing the need for colectomy, at least in the short term," said review co-author Dr. Anthony Kwaku Akobeng.

Akobeng, a gastroenterologist at Manchester Children's University Hospitals in England, and colleagues examined seven randomized controlled studies comprising 860 patients that evaluated infliximab as a treatment for ulcerative colitis.

The review of studies appears in the latest issue of The Cochrane Library, a publication of The Cochrane Collaboration, an international organization that evaluates medical research. Systematic reviews like this one draw evidence-based conclusions about medical practice after considering both the content and quality of existing medical trials on a topic.

"Infliximab is another option if steroids fail," said Peter Higgins, M.D., an assistant professor in gastroenterology at the University of Michigan Medical Center in Ann Arbor.

Still, infliximab "has known infectious risks, which while rare, can be fatal," said Higgins, who was not involved with the review. He added that it's not clear if it's a better option than cyclosporine, another drug commonly used when other medications fail.

The disease afflicts an estimated 600,000 Americans, and occurs when ulcers form in the rectum and colon, leading to frequent diarrhea and bleeding.

According to Higgins, the causes of ulcerative colitis aren't clear, but they may have something to do with an interaction between a person's genetic makeup and another factor, such as infection or the use of non-steroidal anti-inflammatory drugs, a class of painkillers that includes ibuprofen (Advil) and naproxen (Aleve).

The interactions may cause "an abnormal interaction between bacteria in the gut and the immune system," Higgins said.

Meanwhile, "mechanisms that lead to a reduction of inflammation in response to bacterial products are defective, so the body has a hard time 'resetting' itself, and the inflammation becomes chronic," said Gerald Dryden, Jr., M.D., an associate professor at the University of Louisville in Kentucky.

There are a number of drug treatments for colitis, including steroids, which reduce inflammation by dampening the body's immune system, and aminosalicylates, which also help control inflammation.

In some cases, however, the colon must be removed; some patients must use colostomy bags for the rest of their lives.

In recent years, researchers have begun looking at infliximab -- also known by the brand name Remicade -- as a possible treatment for moderate and severe colitis.

In the review studies, patients were given either infliximab or a placebo for moderate and severe cases of ulcerative colitis. All the patients failed treatment with steroids and/or other drugs that suppress the immune system.

Three intravenous infusions of infliximab (at zero, two and six weeks) were 3.2 times more likely than placebos to lead to remission of symptoms and two times more likely to induce a clinical response at eight weeks.

The researchers also found that a single infusion of infliximab was more effective than placebo in reducing the need for colectomy within three months.

Serious side effects were "not common" in the studies, but the authors report that infliximab can be dangerous to some patients.

The drug has been used to treat rheumatoid arthritis and Crohn's disease, an intestinal disorder that is closely linked to colitis. Infliximab appears to tinker with a protein known as tumor necrosis factor alpha that contributes to inflammation.

"There are some theories that this drug works by inducing 'apoptosis,' which means programmed cell death," Dryden said. "In other words, inflammatory cells, which are contributing to the disease state, will 'die' as a result of this medication."

Both Higgins and Dryden praised the review. However, Higgins said a limitation was the small number of studies and Dryden said that the review didn't offer a comparison with cyclosporine.

"Looking at the published studies, infliximab appears to be less effective than cyclosporine, but less toxic," Higgins said. "However, the two agents have never been compared head to head, so it is difficult to know how they would compare in similar patients."

What should patients think about this research? The review suggests that infliximab does benefit patients, Dryden said.

However, it's not clear if the drug actually improves the lives of patients enough that they feel "back to their normal baseline," Dryden said. "There is still room for improvement."

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Health Behavior News Service: (202) 387-2829 or www.hbns.org.

Lawson MM, Thomas AG, Akobeng AK. Tumour necrosis factor alpha blocking agents for induction of remission in ulcerative colitis. Cochrane Database of Systematic Reviews 2006, Issue 3.

The Cochrane Collaboration is an international nonprofit, independent organization that produces and disseminates systematic reviews of health care interventions and promotes the search for evidence in the form of clinical trials and other studies of interventions. Visit http://www.cochrane.org for more information.


Last reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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