April 14, 2010 -- Patients with moderate to severe Crohn's disease are most likely to get better if treated with a combination of biologic and immune-suppressing therapies, a clinical trial suggests.
It's a "landmark trial," says gastroenterologist David Kerman, MD, assistant professor of clinical medicine at the University of Miami Miller School of Medicine, who was not involved in the study.
"This is very important news," Kerman tells WebMD. "It says that combination therapy is actually better in these patients at an earlier point in the disease than previously thought."
The findings already have changed clinical practice, says study researcher William Sandborn, MD, vice chair of gastroenterology at the Mayo Clinic in Rochester, Minn.
The trial enrolled 508 patients. It tested a combination of Remicade and azathioprine, an immunosuppressive drug, against each drug by itself. Remicade is one of three approved "biologic" Crohn's treatments that block TNF, a major player in the immune responses that inflame the intestines of Crohn's patients.
After 26 weeks of treatment, patients getting the combination had a 57% chance of disease remission, compared to 44% of those getting Remicade alone and to 30% of those getting azathioprine alone. Similar results were seen after 50 weeks of treatment.
The combination treatment worked even better in patients with colonoscopy-confirmed disease and blood-test evidence of inflammation. Among these patients, 69% achieved remission with the combination treatment compared to 57% of those on Remicade alone and to 28% of those on azathioprine alone.
"For patients who don't initially respond to corticosteroids, or who don't continue to respond when we taper down corticosteroids, those patients are best treated with a combination of anti-TNF and immune-suppressive drugs, Sandborn tells WebMD. "That will give patients their best chance of being off steroids and having a healthy bowel."
Some specialists are skipping steroids and going straight to the combination, Kerman says.
"Some patients require corticosteroids, but I think that more and more we are realizing that corticosteroids may change the natural history of Crohn's disease for a worse outcome," he says. "Using biological therapies and immune modulators may preclude the need for ever needing corticosteroids."
Combination Treatment for Crohn's: Risk, Cost
The treatment is not without risk. Remicade and other anti-TNF drugs (Humira and Cimzia) increase a patient's risk of life-threatening infections and cancers. So do immune-suppressing drugs, although the Remicade trial suggested that combination therapy is not more risky than azathioprine or Remicade alone.
In the study, 4% of patients receiving the Remicade/azathioprine combination developed serious infections, as did 5% of those in the Remicade-only group and 5.6% of those in the azathioprine-only group.
And the treatment is expensive. A 155-pound patient would need about 350 milligrams of Remicade per treatment. Four 100-milligram vials of Remicade cost $2,763, according to drugstore.com.
Other anti-TNF drugs, which Sandborn and Kerman say should work as well as Remicade, cost about as much. But Kerman notes that anti-TNF therapy for Crohn's disease is actually cost-effective, as the drugs prevent hospitalizations, loss of work, and other expenses.
"I'd like for Crohn's patients to ask their doctors to consider combination treatment with these biologics and immune modulators as an early therapy," Kerman says. "It has been shown that treating much earlier gives them a much better chance of responding, rather than getting the treatment after damage already has been done."
The combination therapy does not cure Crohn's disease. Treatment must continue indefinitely. However, Sandborn says that some of the patients in the earliest clinical trials are still doing well after 12 years of treatment.
Sandborn serves as a consultant to Centocor, which makes Remicade, and to Abbott, which makes Humira. Fees for this consultation go to Mayo Clinic and not directly to him. Kerman is on the speakers bureau for UCB, which makes the anti-TNF drug Cimzia.
Sandborn and colleagues report the finding of their trial in the April 15 issue of the New England Journal of Medicine.