Studies highlight benefits of three novel therapies for inflammatory bowel disease

May 21, 2004

Two studies performed by University of Chicago researchers and presented at the annual Digestive Disease Week (DDW) meeting in New Orleans provide encouraging results from clinical trials of novel drugs to treat inflammatory bowel disease--ulcerative colitis and Crohn's disease. Both were featured in DDW press briefings.

"Ten years ago we had very few options for treatment of inflammatory bowel disease," said Steve Hanauer, MD, professor of medicine and clinical pharmacology and section chief of gastroenterology at the University of Chicago Medical Center. "Five years ago we presented the results from infliximab, the first precisely targeted drug developed for IBD, a major step forward for the field. And now this year we have several promising new options, a remarkable example of how quickly the field is changing."

Hanauer and colleagues presented results for oral OPC-6535 and adalimumab.

1. Randomized, double-blind, placebo-controlled, parallel arm, safety and efficacy trial of once-daily, oral OPC-6535 in the treatment of active ulcerative colitis

OPC-6535 is a new class of anti-inflammatory agent, a phophodiasterase inhibitor. In this phase II trial, 186 patients with mild to moderate ulcerative colitis were randomized to receive an oral, daily dose of either 25 mg. or 50 mg. of OPC-6535 or placebo for eight weeks. The trial measured changes in the Disease Activity Index (DAI: scale of 1 to 12) from the beginning to week eight. After eight weeks, 55 percent the 25 mg. group and 48 percent of 50 mg. group showed clinical improvement, defined as a three-point reduction in DAI, compared to only 40 percent of those taking placebo. Responses were greater for those with more severe disease (DAI of 7-11).

"The OPC-6535 results are encouraging in the treatment of ulcerative colitis, especially in patients with greater disease severity," said Dr. Hanauer. "We are excited to find a new agent that may play a role in treating the induction and maintenance stages of this disease."

Adverse events reported in clinical studies with OPC-6535 included mild headache and nausea that were dose related and abated over time. Larger dose-ranging trials in active disease and maintenance of remission are currently underway.

2. Clinical assessment of adalimumab safety and efficacy studied as induction therapy in Crohn's disease (CLASSIC)

In a study involving 299 patients treated with placebo or one of three doses of adalimumab (a "humanized" version of infliximab, sold under the trade name HUMIRA®), researchers found that the drug was well tolerated and produced responses similar to infliximab; 30 percent of patients achieved remission within four weeks. Adalimumab was designed to reduce the likelihood of an immune reaction that many patients develop with infliximab.

A smaller, related clinical trial at the University of Chicago Hospitals and the Mayo Clinic found that adalimumab was a safe and effective treatment option for Crohn's disease patients who failed or became intolerant to infliximab. In this uncontrolled trial, involving difficult-to-treat patients, adalimumab was well tolerated for 12-weeks in all 24 patients, including 14 who previously experienced treatment-limiting acute hypersensitivity reactions to infliximab and six who previously experienced delayed hypersensitivity reactions with infliximab. Maintenance trials to prevent relapse in Crohn's with adalimumab are currently in progress.

Humira is already approved for use in rheumatoid arthritis and "the promising results for adalimumab give physicians another option for patients suffering from Crohn's," said Hanauer. "In the past, physicians who saw patients unable to tolerate infliximab were handcuffed. This will help them to give patients another chance at improving their quality of life. In addition," said Hanauer, "because adalimumab is self-injected instead of administered by infusion, it presents patients with a more convenient treatment option and avoids the infusion reactions that can occur with other some of the other drugs in current use."

In addition to the aforementioned trials, investigators at the University of Chicago also participated in a maintenance trial of natalizumab.

3. Efficacy of natalizumab for maintaining clinical response and remission after active Crohn's therapy (ENACT-2)

In this study, 339 Crohn's disease patients who had already responded to treatment received either placebo or 300 mg of natalizumab (trade name Antegren®) every four weeks for 12 months. The drug was designed to prevent the emergence of "adhesion molecules," within blood vessels. These molecules induce the white blood cells responsible for inflammation to leave the blood vessels and infiltrate tissue.

In this trial, 44 percent of patients who received natalizumab remained in remission at six months compared to only 26 percent of those who did not get the drug. The researchers also found hat 55 percent of patients taking natalizumab were able to stop taking steroids, compared to only 25 percent of those who did not get the medication.

There were no significant differences in rates of serious and non-serious adverse events between placebo and natalizumab.

"This provides us with another way to maintain remissions in patients who respond to induction therapy with natalizumab" said Hanauer.

Background on inflammatory bowel disease: Crohn's disease and Ulcerative colitis

Crohn's disease affects approximately 500,000 Americans, typically beginning in late childhood or early adulthood. The disease causes inflammation of the gastrointestinal tract. It can result in diarrhea, fever, abdominal pain and weight loss. In up to 30 percent of patients, Crohn's disease causes fistulas--openings that burrow through the bowel wall into nearby organs or through the surface of the skin.

Ulcerative colitis also affects some 500,000 Americans. It causes inflammation of the inner lining of the colon (large intestine) and the rectum. Symptoms range from mild to severe, including persistent diarrhea, abdominal pain, rectal bleeding, fever, weight loss, skin or eye irritations, and delayed growth and sexual maturation in children.

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