Investigations
Remission for Crohn's patients

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Receiving regular infusions of an antibody called infliximab can prolong remissions in patients with moderate to severe Crohn's disease, reports Stephen Hanauer, a professor of medicine.

In the first large-scale trial of infliximab (marketed as Remicade) patients who received infusions every eight weeks were twice as likely to be in remission after 30 weeks of therapy as those not receiving the drug. The regular infusions kept patients in remission for twice as long as those on a placebo, and even longer for those receiving a higher dose.

"At last we have a therapy that truly allows us to manage this disease over time, rather than just treating flareups," says Hanauer, lead investigator of a multi-center research team that published its findings in the May 4 Lancet. "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, as well as diarrhea, fever, abdominal pain, and weight loss. Up to 30 percent of patients develop fistulas-openings that burrow through the bowel wall into nearby organs or to the skin's surface. Enter infliximab, which blocks the activity of a key inflammatory mediator called tumor necrosis factor alpha (TNF-a). The drug attaches to and neutralizes TNF-a both on the cell membrane and in the blood, thereby preventing inflammation.

All of the 335 patients with moderate to severe Crohn's disease in the trial-at 55 centers in North America, Europe, and Israel-received an initial dose of infliximab. Patients in one group then received a placebo in the study's second and sixth weeks and again every eight weeks. Another group received 5 mg/kg of infliximab on the same schedule. Meanwhile, a third group received 5 mg/kg of infliximab at weeks two and six, followed by 10 mg/kg every eight weeks beginning at week 14.

By the trial's 30th week only 20 percent of patients on the placebo had no symptoms, while nearly 39 percent of those on the lower dose of infliximab and 45 percent of those on the higher dose were in complete remission. And infliximab recipients had longer-lasting remissions than the median 19 weeks experienced by those on the placebo. At the lower dosage remissions lasted about 38 weeks; at the higher dosage, more than 54 weeks.

Infliximab also helped patients reduce their reliance on steroids. In fact, patients who received the drug for 30 weeks were able to completely eliminate steroid use. This is important because corticosteriods have traditionally 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. That's not to say infliximab is without side effects: because the drug suppresses part of the immune response, it may increase the risks of serious infections as well as the possibility of upper respiratory infections, cough, sinusitis, and rashes.

Still, says Hanauer, "it would make a real difference for patients if we had alternatives to steroids or better ways to reduce the steroid dose."
-J.E.

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