New Drugs Target Bowel Disease

Take aim at specific troublesome proteins, enzymes

WEDNESDAY, May 19, 2004 (HealthDayNews) -- For the millions of Americans who suffer from digestive diseases such as inflammatory bowel disease or Crohn's disease, a host of new drugs offer hope, according to new research.

Experts gathering in New Orleans for Digestive Diseases Week said at a teleconference Tuesday that many of the medications show promise because they deliver targeted rather than general attacks against the disease-causing process.

Among the new remedies discussed, a drug called OPC-6535 was effective for those with moderately severe ulcerative colitis, said study author Dr. Stephen Hanauer, a professor of medicine and clinical pharmacology at the University of Chicago Pritzker School of Medicine.

Ulcerative colitis causes inflammation and sores called ulcers in the large intestine lining. Hanauer's team gave 186 patients either the drug or placebo for eight weeks. The drug dose was either 25 milligrams or 50 milligrams once a day. More than half of the 25-mg tablet group and 48 percent of the 50-mg group showed improvement in symptoms, he said. Symptoms can include diarrhea, weight loss, fatigue and rectal bleeding.

"Patients who had more moderately active disease were the better responders," Hanauer said. The drug is thought to work because it blocks an enzyme and controls the immune response that leads to inflammation.

A monoclonal antibody called basiliximab (anti-CD25, or Simulect) looks promising to treat ulcerative colitis that has been resistant to the conventional treatment with steroids, said Dr. Tom Creed, a clinical research fellow at the Henry Wellcome laboratories of the University of Bristol in the United Kingdom.

Monoclonal antibodies, produced by making identical offspring of a single, cloned antibody producing cell, can be used to target specific proteins involved in the immune response.

In all, Creed looked at 20 patients with moderate disease and 10 with severe disease. "In our severe group, 50 percent got better and full remission. In the moderate group, 95 percent improved."

For Crohn's disease, which causes inflammation in the small intestine and is accompanied by rectal bleeding, abdominal pain and diarrhea, Hanauer and his team found adalimumab, a human monoclonal antibody, is effective.

The team evaluated 299 patients with active disease; 30 percent of those who got the adalimumab had clinical remission, compared to just 12 percent of those on placebo.

The treatment is a new type of monoclonal antibody, he said. Unlike other monoclonal antibodies, in which the antibody-forming cells are isolated from a mouse's spleen, this one is fully human, he said.

Another monoclonal antibody called natalizumab (brand name Antegren) helped Crohn's patients in another study. Dr. Brian Feagan of the University of Western Ontario gave 339 patients with Crohn's either the monoclonal antibody or placebo to see if response could be maintained. It worked better than a placebo to sustain response and remission.

At six months, 61 percent of those treated with the monoclonal antibody continued to be in remission, compared to only 29 percent of those on placebo. "I think this drug will be a welcome addition to our armamentarium in the treatment of Crohn's disease," he said.

Yet another monoclonal antibody, fontolizumab (brand name Huzaf), helped other Crohn's disease patients, said Dr. Tillman Pearce, senor director of clinical research for Protein Design Labs in Fremont, Calif. He tested it in 133 patients and found two infusions resulted in a beneficial effect on disease activity.

Another researcher reported success in treating Crohn's with intestinal worms, or helminths, which work by suppressing the immune response and thus reducing the disease symptoms. In the study, Dr. Joel Weinstock, a professor of internal medicine at the University of Iowa Carver College of Medicine, gave 29 patients the so-called ova therapy in a drink every two weeks for 24 weeks. At the end, 79 percent of patients had a response and 72 percent were in remission. "This may prove to be an effective new treatment," he said.

More information

To learn more about digestive diseases, visit the National Digestive Diseases Information Clearinghouse and American Gastroenterological Association.

SOURCES: May 18, 2004 teleconference, Digestive Disease Week annual conference, New Orleans
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