From Under The Miscroscope, which is the Research News Bulletin from the Crohn’s & Colitis Foundation of America, Winter 2003
This year 3200 gastroenterologists participated in the ACG (American College of Gastroenterology) Annual Meeting.
The only biologic drug approved for treating moderate to severe Crohn’s disease, infliximab, continues to be studied. Administered by intravenous infusion, this therapy was approved by the FDA (Food & Drug Administration) in 1998, and the data continues to accumulate on the best practices for its use. Results of the ACCENT 1 trial, a study of more than 500 patients, determined that infliximab could not only bring about remission, but maintain it. Based on this data, the FDA approved a new maintenance indication for infliximab in June of 2002. One of the hot topics at the AGC concerned patients with strictures (a narrowing of the intestine) and the potential for bowel obstruction (complete or partial blockage) in these patients. Dr. Gary Lichtenstein, University of Pennsylvania, found that individuals in the ACCENT 1 study who had received higher amounts of infliximab were less likely to develop intestinal strictures that lead to bowel obstruction.
A second study compared two groups of patients: one group who had known intestinal strictures and another group who had received infliximab but did not have strictures. None of the patients with known strictures developed a complete bowel obstruction at a later time. Interestingly, patients with strictures were less likely to respond to infliximab than those without. These studies suggest that infliximab does not lead to strictures. Therefore, patients who have strictures can be safely treated with this drug, although their response rate may be lower. The lower response rate is probably due to the fact that these people have advanced disease; strictures are more common in such patients.
Trials that test the effectiveness of infliximab in ulcerative colitis are underway. Visit www.ccfa.org for more information about these and other clinical trials.
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NEW YORK (Reuters Health) – More than half of all people who repeatedly take the drug infliximab for Crohn’s disease develop antibodies to the drug, which may reduce its effectiveness, the results of a new study suggest.
But treatment with immune-suppressing drugs may help maintain the effectiveness of the medication, researchers say.
Crohn’s disease is a type of inflammatory bowel disease with symptoms that include pain, abdominal cramps, diarrhea, bleeding and weight loss. Drugs and surgery to remove the portion of the intestine affected by the disease may relieve symptoms, but there is no cure.
Infliximab (Remicade) is monoclonal antibody that neutralizes the activity of an immune protein called tumor necrosis factor that is thought to be involved in the inflammation of Crohn’s disease.
In 1998, infliximab became the first drug to gain US approval as a Crohn’s treatment. The drug was approved to treat people with moderate-to-severe Crohn’s disease who are not adequately helped by other treatments, including steroids and antibiotics. It is also approved for people with Crohn’s who have fistulas, which are abnormal passages that can develop in the bowel.
It has been known that the immune system sometimes produces antibodies in response to infliximab infusions. The presence of antibodies can cause patients to have reactions to infusions. There is also some concern that the antibodies may shorten the duration of the drug’s effects.
In a study of 125 people who received infliximab to treat Crohn’s disease, Dr. Paul Rutgeerts and colleagues found that 61% had developed antibodies to infliximab by the time they had received five infusions of the drug.
Having high levels of antibodies seemed to diminish the effectiveness of the drug, the investigators report in the February 13th issue of The New England Journal of Medicine. People with high levels of antibodies had an average 35-day break between infusions, compared with a 71-day break in people with lower levels of antibodies.
People with high antibody levels were also more than twice as likely to have an infusion reaction. Levels of infliximab in the body were significantly lower in people who experienced such a reaction.
Although antibodies to infliximab often developed, it may be possible to prevent them by treating patients with immune-suppressing drugs, Rutgeerts, of the University Hospital Gasthuisberg in Leuven, Belgium, told Reuters Health. In the study, people who were on such drugs tended to have lower levels of antibodies and higher levels of infliximab four weeks after treatment.
Rutgeerts said that not everyone taking infliximab needs to be screened for antibodies. But screening may be useful in people who have experienced infusion reactions or who have become less responsive to the drug, he said.
If high levels of antibodies are detected, Rutgeerts said that increasing the dose of infliximab, giving the drug every eight weeks and giving immune-suppressing drugs may be helpful.
But Rutgeerts added, “It is not clear, however, whether you can go on with this treatment for years.”
Several of the researchers have served as consultants or speakers or have received funding from Centocor and Schering-Plough, which both market infliximab.
SOURCE: The New England Journal of Medicine 2003;348:601-608. Last Updated: 2003-02-12 17:04:26 -0400 (Reuters Health) By Merritt McKinney
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Strictures and Remicade
One of the hot topics at the ACG (American College of Gastroenterology) concerned patients with strictures (a narrowing of the intestine) and the potential for bowel obstruction (complete or partial blockage) in these patients. Dr. Gary Lichtenstein, University of Pennsylvania, found that individuals in the ACCENT 1 study who had received higher amounts of infliximab were less likely to develop intestinal strictures that lead to bowel obstructions.
A second study compared two groups of patients: one group who had known intestinal strictures and another group who had received infliximab but did not have strictures. None of the patients with known strictures developed complete bowel obstruction at a later time. Interestingly, patients with strictures were less likely to respond to infliximab than those without. These studies suggest that infliximab does not lead to strictures. Therefore, patients who have strictures can be safely treated with this drug, although their response rate may be lower. The lower respose rate is probably due to the fact that these people have advanced disease; strictures are more common in such patients.
Updated September- 2003