The May 1999 issue of the New England Journal of Medicine published a report that gives the first definitive clinical evidence that a medical therapy can close fistulas, a complication of Crohn disease which is an autoimmune gastrointestinal disease. Results from this landmark study showed that infliximab (trade name REMICADE) can be effective in healing fistulas.
Daniel Present, M.D., the lead author of the study, is a Clinical Professor of Medicine at Mt. Sinai Medical Center in New York. This study is important because it is the first to document the beneficial effect of an agent in reducing the number of fistulas experienced by individuals with Crohn disease. In the study, many patients treated with infliximab were shown to have experienced an improved quality of life.
Fistulas, deep ulcer tracts that burrow through the bowel wall into nearby organs or through the surface of the skin, are experienced by approximately one-third of the individuals with Crohn disease. As many as three-quarters of persons with Crohn disease will need surgery at some time during the course of their disease.
Results from the randomized, double-blind, placebo-controlled study with 94 patients showed that more than two-thirds of the patients receiving REMICADE (68 percent) achieved closure of, at a minimum, half of their draining fistulas compared with 26 percent of placebo-treated patients. More than half of the patients receiving REMICADE (55 percent) experienced closure of all their fistulas compared with 13 percent of placebo-treated patients. The average time for response was two weeks, with an average period of improvement lasting three months.
The study, which was conducted at 12 centers in the United States and Europe, concluded that the maximum beneficial effect can be achieved by the smallest dose tested: 5 mg/kg. One patient in the study who was scheduled to receive surgery for her fistulas when she became involved in this clinical trial was able to cancel the surgery because of her improvement. The beneficial effect of this treatment was found to be consistent regardless of concomitant therapy with other commonly used Crohn disease treatments. Studies are also looking at REMICADE for the treatment of children with Crohn disease.
Throughout the trial, the most common adverse reactions included headache, abscess, upper respiratory tract infection, and fatigue. Four patients experienced mild dizziness, slight temperature elevation, headache, or chest pain with flushing during or shortly after an infusion.
REMICADE was approved by the Food and Drug Administration (FDA) in August of l998 for treatment of moderately to severely active Crohn disease among patients who have an inadequate response to conventional therapy. It was also approved for the treatment of fistula(s). This treatment is the first of a new class of agents that block activity of an inflammatory mediator called tumor necrosis factor alpha, TNF-(alpha). Overproduction of TNF-(alpha) leads to inflammation in autoimmune conditions such as Crohn, rheumatoid arthritis, and many other autoimmune diseases. It is believed that it reduces inflammation in patients with Crohn disease by binding to and neutralizing TNF-(alpha) on the cell membrane and in the blood.
Note: The study was sponsored by Centocor, Inc., the company that manufactures REMICADE. This information is for the purpose of information and is not meant as an endorsement of any product. AARDA encourages patients to discuss any questions with their physicians.
Sources: New England Journal of Medicine; Mt. Sinai Medical Center
