Study shows infliximab can prolong remissions in Crohn's disease

May 2, 2002

Sustained treatment with the monoclonal antibody infliximab can prolong remissions in patients with moderate to severe Crohn's disease reports a multi-center research team in the 4 May 2002, issue of The Lancet.

In the first large-scale trial of infliximab (marketed as REMICADE) used as maintenance therapy instead of as a treatment for acute attacks, researchers found that patients who received infusions of infliximab every eight weeks were twice as likely to be in remission after 30 weeks of therapy as those who were not receiving the drug. Bi-monthly infusions kept patients in remission for twice as long, even longer at a higher dose.

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

Crohn's disease, a chronic inflammatory bowel disorder, affects approximately 500,000 Americans, typically beginning in their teens and early 20s. The disease causes inflammation of the gastrointestinal tract. It causes diarrhea, fever, abdominal pain and weight loss. In up to 30 percent of patients, Crohn's disease causes fistulas--openings that burrow through the bowel wall into nearby organs or through the surface of the skin.

The researchers enrolled 573 patients with moderate to severe Crohn's disease at 55 centers in North America, Europe, and Israel. All patients received an initial dose of infliximab. The 335 patients (58%) who responded to the initial dose within 2 weeks were randomized to one of three treatment groups.

Group I received placebo (an infusion containing no medication) at weeks 2 and 6 of the study, then every eight weeks. On the same schedule, group II received 5mg/kg of infliximab, and group III received 5 mg/kg of infliximab at weeks 2 and 6 followed by 10mg/kg beginning at week 14.

By week 30, patients in groups II and III were twice as likely to be in remission as patients in group I, who received only the placebo. Only 20 percent of the patients receiving placebo had no symptoms at 30 weeks. But nearly 39 percent of those on the lower dose of infliximab, and 45 percent of those on the higher dose, were in complete remission.

Patients who had sustained treatment also had longer-lasting remissions. For patients receiving placebo, remissions lasted a median of 19 weeks. For those receiving 5mg/kg of infliximab, they lasted twice as long, a median of 38 weeks. For those receiving 10mg/, the average was greater than 54 weeks.

Infliximab also helped patients reduce their reliance on steroids. The majority of patients taking steroids at the beginning of the trial and who received the maintenance regimen of inflixmab for 30 weeks were able to completely eliminate their steroid use. Patients who had received only a single dose had to continue to use steroids.

Patients receiving infliximab also reported higher quality-of-life scores at week 30 than patients receiving the placebo.

"We also found that many patients who has lost their response to the drug benefited from re-treatment at intervals shorter than every eight weeks," said Hanauer.

Reports of side effects were the same in all three groups.

Corticosteriods have been the first-line therapy for patients with moderate to severe Crohn's disease. Yet patients who use steroids for a long time often suffer a wide array of side effects, including osteoporosis, diabetes, difficulty sleeping, mood swings, and possible dependency.

"It would make a real difference for patients if we had alternatives to steroids, or better ways to reduce the steroid dose," said Hanauer.

Infliximab is a monoclonal antibody that blocks the activity of a key inflammatory mediator called tumor necrosis factor alpha (TNF-a). Overproduction of TNF-a leads to inflammation in conditions such as Crohn's, rheumatoid arthritis and other autoimmune diseases. Infliximab was designed to attach to and neutralize TNF-a on the cell membrane and in the blood.

Because it suppresses part of the immune response, infliximab may increase the risks of serious infections. There are also reports of serious infusion reactions with hives, difficulty breathing, and low blood pressure. In clinical studies, some people experienced upper respiratory infections, headache, cough, nausea, sinusitis or mild reactions such as rash or itchy skin. In rare cases, people with de-myelinating disease who were treated with infliximab have seen their symptoms intensify.

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