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Crohn's Treatment Receives FDA Approval


Crohn's disease plagues an estimated 500,000 Americans, causing inflammation of the gastrointestinal tract, diarrhea, fever, abdominal pain, and weight loss. Some patients also develop fistulas and other complications.

While this chronic inflammatory bowel disease causes havoc, researchers have been racing to develop pharmaceuticals to attack the problem where it seems to cause the most damage--the intestines. Scientists at AstraZeneca of Wilmington, Del., have created Entocort EC to treat patients with mild to moderate forms of the disease. Entocort EC, known as budesodine generically, is a steroidal drug that is released specifically in the intestine, which limits the amount of the drug entering the systemic circulation. Taken once daily, it has been found to reduce inflammation.

The chief medical officer of GI products for AstraZeneca has said the release of the drug into the intestines is a significant change from other drugs currently on the market for Crohn's.

"Prednisone and prednisolone are largely systemically absorbed. They can produce fairly significant side effects. The difference with the new drug Entocort is that it tends to work more topically in the gut where the Crohn's disease is active, and once it gets absorbed, it is much more rapidly metabolized so the systemic exposure following absorption is much less than that of others. The kind of side effects one might see with steroids have been shown to be much less with Entocort," said Doug Levine, MD. "What has been specifically examined is the steroid-class side effects one might see and in comparative studies looking at Entocort vs. prednisone. You can see significantly less of these steroid-class side effects (with Entocort).

In five clinical trials involving an estimated 1,000 patients the following side effects were reported: headache, respiratory infection, nausea, and symptoms of hypercorticism. Entocort EC is also contraindicated in patients with known hypersensitivity to budesonide.

The US Food and Drug Administration (FDA) approved the locally active glucocorticosteroid drug for flare-up treatment Oct. 3, 2000. One physician said the need for such drugs is in high demand.

"The FDA approval of Entocort EC signals an important advance in the treatment of Crohn's disease--a disease for which there is a significant need for new medicines," said William J. Sandborn, MD, professor of medicine, Mayo Medical School and Head of Inflammatory Bowel Disease Research, Mayo Clinic.

Crohn's disease has been particularly difficult for physicians to treat because of the extent of potential damage.

"It is a disease characterized by inflammation and scarring so even once the inflammation is taken care of, you may have residual scarring effects that may leave the patient with some level of persistent symptoms," Levine said.

Also, patients are often frustrated with the lack of recognition the disease receives in comparison to other illnesses.

"To some degree, from the patient's view point, the disease is either under recognized or under treated, because unlike heart or lung disease where patients will have more visible (symptoms), ... until you've had inflammation and had a disruption of absorption of nutrients, patients with damage to the GI tract may not look particularly ill. So it is sometimes a disconnect with the general appearance of the patient and the actual disease severity in the GI tract," he said.

However, Lisa H. Richardson, chairperson of the board for the Crohn's & Colitis Foundation of America, said Crohn's patients should be optimistic.

"Although Crohn's can be a debilitating and difficult disease to live with, patients should be encouraged by the recent advances in the research around this complex disease area," she said.

The recommended adult dosage for Entocort EC is 9 mg (three 3 mg capsules) taken once daily in the morning for up to eight weeks. Although researching the possibility, Entocort has not been approved for long-term treatment.

"The drug has been approved for flare ups," Levine said. There certainly have been investigations looking at the ability of the drug to maintain remission. We did not seek approval to promote that as a specific use of the drug."

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Resource Guide

Web Sites Dedicated to Crohn's Disease

Crohn's & Colitis Foundation of America

Crohn's Disease, Ulcerative Colitis, Irritable Bowel Disease Pages

Healing Well

National Association for Colitis & Crohn's Disease (UK)

National Digestive Disease Information Clearinghouse

Long-Term Treatment Option for Crohn's

The first large-scale trial of infliximab has shown the pharmaceutical can prolong remission in patients suffering from moderate to severe Crohn's disease.

Crohn's disease is a digestive disorder that plagues nearly half a million Americans.

Occasional treatment with the monoclonal antibody infliximab (also known as Remicade) was studied in a clinical trial of 573 patients. Each of these patients, all of who experienced either moderate or severe Crohn's disease, received an initial dose of infliximab. Those patients who responded to the drug were randomized into one of three trial groups.

The first group received a placebo. The second group was given 5mg/kg of infliximab and the third group received 5 mg/kg initially and then increased to 10 mg/kg for the final three infusions. Each group was given an infusion at weeks 2, 6, 14, 22, and 30.

Those in groups two and three were twice as likely to be in remission by week 30 than those patients in group one who received the placebo.

"This is the first therapy that truly allows us to manage this disease over time, rather than just treating flare-ups," said Stephen Hanauer, MD, lead investigator and director of the study and professor of medicine at the University of Chicago. "Ongoing treatment with infliximab decreased disease activity, prevented sudden attacks, and enabled patients to reduce or, in many cases, completely eliminate steroids."

Infliximab is a monoclonal antibody that prevents the key inflammatory mediator, tumor necrosis factor alpha, from producing. Overproduction of the mediator can cause inflammation in Crohn's, rheumatoid arthritis, and other patients suffering from autoimmune diseases. The drug is thought to work by binding to and neutralizing tumor necrosis factor alpha on the cell membrane and in the blood, thereby reducing inflammation.

However, because this drug must work against a fraction of the immune system to be successful, there are risks of serious infections including sepsis and tuberculosis. Other related symptoms reported include: hives, difficulty breathing, and low blood pressure. Some patients with demyelinating disease have reported intensified symptoms when treated with infliximab. Side effects include: upper respiratory infections, headache, cough, nausea, sinusitis, or mild reactions including rash and itchy skin.

Remicade is manufactured by Centocor Inc., a biopharmaceutical company in Malvern, Penn. The drug has been approved by the US Food and Drug Administration (FDA) to treat both rheumatoid arthritis and Crohn's disease.

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FDA Approves Zollinger-Ellison Syndrome Drug

By Kelli M. Donley

The US Food and Drug Administration (FDA) has approved an expedited schedule for Protonix IV for the treatment of pathological hypersecretory conditions associated with Zollinger-Ellison syndrome.

Manufactured by American Home Products, Protonix, known as pantoprazole sodium generically, is the first intravenous proton pump inhibitor approved in the US for this disease. Zollinger-Ellison syndrome is a rare disease that causes pancreatic and duodenum tumors that are cancerous 50% of the time. These tumors produce gastrin, causing stomach and duodenum peptic ulcers. The cause of the disease is unknown, although it is thought to be from an abnormal tumor suppressor gene. Symptoms include: nausea, vomiting, fatigue, weakness, and weight loss. Treatment options include pharmaceuticals, removal of the tumors, and gastrectomy for patients not responding to other options.

This IV treatment was created for patients who are unable to take oral medications. Previous to the FDA approval, these patients would have received an IV H2 receptor antagonist.

Joseph R. Pisegna, MD, chief of Gastroenterology and Hepatology at the VA Greater Los Angeles Healthcare System in Los Angeles, Calif., said clinical trials showed the drug was helpful in this painful and potentially fatal disease.

"In clinical trials, Protonix IV acted quickly, within one hour, and maintained continuous acid control for up to 24 hours, making a critical difference for my patients," he said. "In fact, in several of these patients, Protonix clearly played a life-saving role."

The drug is a proton pump inhibitor and the fact it is administered through an IV helps patients who are suffering from severe ulcers.

"Its function is to irreversibly bind to the proton pump and thereby inhibit acid production," said Pisegna. "Because it is directly administered into the bloodstream and doesn't require absorption, ... we are able to control acid secretion quite rapidly with it--generally within an hour."

Some Zollinger-Ellison syndrome patients also require the drug in the perioperative state because they are producing so much acid. They are at a higher risk for ulcers and GI bleeding. Additionally, patients who have gastronomas removed may undergo chemotherapy and be nauseous. Pisegna said because Protonix is given via IV, the patients do not have to worry about digesting oral medications.

Proton pump inhibitors are one of the largest classes of medications prescribed in the US. Protonix is marketed by Wyeth-Ayerst Laboratories in the US.

For more information about the drug, log onto: 

Did You Know?

Zollinger-Ellison syndrome was discovered by Robert M. Zollinger and Edwin H. Ellison, both US surgeons. The condition is caused by gastrin-secreting pancreatic and duodenum tumors. A characteristic of the syndrome is large amounts of hydrochloric acid and pepsin that cause ulceration of the stomach and small intestine. Gastrectomy and removal of the pancreatic/duodenum tumors can cure the syndrome if metastasis has not occurred.

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