Study shows infliximab can maintain long-term remissions in Crohn’s disease

May 21, 2000

Periodic treatment with the monoclonal antibody infliximab can prolong remissions in patients with moderate to severe Crohn's disease, a multi-center research team reports today at the Digestive Disease Week meeting in Atlanta.

The ACCENT-I clinical trial is the first large-scale trial of infliximab (also known as REMICADE) used as maintenance therapy instead of as a treatment for acute attacks. The researchers found that after 30 weeks of therapy, patients receiving infusions of infliximab every eight weeks were twice as likely to be in remission as those who received only a single dose of the drug but no follow-up infusions.

"This is the first 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."

Infliximab was well tolerated throughout the 30 weeks of this trial without any unanticipated side effects.

Crohn's disease, a chronic inflammatory bowel disorder, affects approximately 500,000 Americans, typically beginning in late childhood or early adulthood. The disease causes inflammation of the gastrointestinal tract. It can result in 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 (58.5 percent) who responded to the initial dose were randomized to one of three treatment groups.

All three groups received infusions at weeks two, six, 14, 22, and 30 of the study. Group I received placebo (an infusion containing no medication), group II received 5 mg/kg of infliximab, and group III received 5 mg/kg of infliximab at weeks two and six followed by 10mg/kg at weeks 14, 22, and 30.

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.

Nearly 21 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.

Infliximab also helped patients reduce their reliance on steroids. The median steroid dose decreased by 15 mg/day for those on the lower dose and 13.8 mg/day for those on the higher dose, versus 10 mg/day for those on one infusion followed by placebo. Most patients who were taking steroids at the beginning of the trial and who received the maintenance regimen of infliximab for 30 weeks were able to completely eliminate their steroid use. Patients who had received only a single dose had to continue steroid use.

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

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

Corticosteroids 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 was approved by the Food and Drug Administration in 1998 for the short-term treatment of moderate to severe Crohn's disease in patients who have an inadequate response to conventional therapy. It is the only non-steroidal medication indicated for the treatment of fistulas.

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. It is believed that infliximab reduces inflammation in patients with Crohn's disease by binding to and neutralizing 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, including sepsis and tuberculosis. These infections may be life threatening. There are also reports of serious infusion reactions with hives, difficulty breathing, and low blood pressure. In rare cases, people with de-myelinating disease who were treated with infliximab have seen their symptoms intensify.

In clinical studies, some people experienced the following side effects: upper respiratory infections, headache, cough, nausea, sinusitis or mild reactions to the infusion such as rash or itchy skin.

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