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Immunomodulators aid infliximab against Crohn's: agents cut in half the rate of antibody development in patients receiving episodic infliximab treatment.

ORLANDO, FLA. -- Infliximab is one of the last treatment options for patients with Crohn's disease who have not responded to other therapies, so it's important to maximize both its short-term and long-term efficacy. Stephen Hanauer, M.D., said at the annual meeting of the American College of Gastroenterology.

"In my view, that means including the use of immunomodulatory therapy," said Dr. Hanauer, professor of medicine and pharmacology and director of gastroenterology at the University of Chicago. Studies suggest that the proportion of patients responding to a single dose of infliximab is higher among those also receiving immunomodulators, Dr. Hanauer noted.

Another important strategy for maximizing treatment efficacy is to administer infliximab as maintenance therapy, rather than episodic therapy, to help prevent development of antibodies to infliximab.

About one-third of patients who receive episodic infliximab treatment develop antibodies, but less than 10% of those receiving 5-10 mg/kg of infliximab for maintenance therapy after a three-dose induction regimen develop antibodies, he explained.

Adding immunomodulators to the treatment regimen will further reduce the risk of antibody development. This is true in patients treated episodically and in patients on maintenance therapy. When immunomodulators are added, the rate of antibody development is cut in half among patients who receive episodic treatment, and at least another 50% reduction in the risk of antibody development is seen among patients on maintenance therapy who also receive immunomodulators.

Reducing antibody development is important because antibodies adversely affect the pharmacokinetics of infliximab and can lead to reduced intervals between infusions and, eventually, loss of response. Antibodies also appear to increase infusion reactions.

Use the three-dose infliximab induction regimen along with maintenance therapy and concurrent immunomodulators to reduce the impact of antibodies, Dr. Hanauer advised. At least one study suggests that administering high doses of steroids before infliximab therapy might also be helpful, he added.

When patients do develop antibodies, try shortening the interval between infusions, or try increasing the dosage from 5 mg/kg to 10 mg/kg. This won't increase toxicity, but it will improve pharmacokinetics, he said.

If a patient loses response to infliximab, first do a reassessment to confirm that the patient really has inflammatory symptoms and not some other potential cause of symptoms, such as short bowel syndrome, that requires a different medication or surgery.

If the patient does have inflammatory symptoms as shown, for example, by elevated C-reactive protein levels or active disease on x-ray, check for antibodies to infliximab, but do this only after 4 weeks have passed since the last treatment to avoid inconclusive results, Dr. Hanauer advised.

If antibodies are present, consider treating the patient with an alternative anti-tumor necrosis factor drug. If no antibodies are detected, and there is no infliximab in the patient's system, shorten the interval between infusions or increase the dosage from 5 mg/kg to 10 mg/kg, he suggested.

If antibodies are detected and infliximab is found in the patient's system, an alternative therapy is needed.

Patients with loss of response or with an allergic reaction (which would most likely be due to antibodies) usually will respond to an alternative anti-tumor necrosis factor drug, he said.

BY SHARON WORCESTER

Tallahassee Bureau
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Title Annotation:Gastroenterology
Author:Worcester, Sharon
Publication:Internal Medicine News
Geographic Code:1USA
Date:Dec 15, 2004
Words:526
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