Like throwing oil on a fire or prescribing a high cholesterol diet for heart patients, gastroenterologists traditionally have believed that it would not be a good idea to stoke up the body's immune system to treat Crohn's disease.
Most treatments for Crohn's, an autoimmune disorder, are geared to suppress the immune response, but a new study demonstrates that stimulating innate immunity also is effective at improving symptoms in many patients with the intestinal disorder.
Reporting this week in the New England Journal of Medicine, researchers from Washington University School of Medicine in St. Louis, Massachusetts General Hospital and other institutions found that treatment with GM-CSF (granulocyte macrophage colony stimulating factor) alleviated symptoms of Crohn's disease and improved patients' quality of life. Patients who received the drug also had significantly less inflammation in the mucosal linings of their intestines.
"That's very significant," says first author Joshua R. Korzenik, M.D., who did much of the research at Washington University and now is co-director of the Crohn's and Colitis Center at Harvard-affiliated Massachusetts General Hospital. "We have clear, clinical evidence that patients feel better and have less pain and other problems related to Crohn's disease. Endoscopic evidence also seems to demonstrate the drug helps with underlying inflammation."
Crohn's affects about half a million people in the United States. A typical Crohn's disease patient deals with diarrhea, abdominal pain and intra-abdominal infections. Frequently, scar tissue closes off sections of the intestine, and patients need surgery to eliminate those blockages.
Korzenik and co-principal investigator Brian K. Dieckgraefe, M.D., Ph.D., a Washington University gastroenterologist and staff physician at Barnes-Jewish Hospital, have been investigating the treatment of Crohn's disease by enhancing the body's innate immunity since the mid-1990s.
"The idea of priming the immune system in patients with Crohn's disease sounds a bit crazy at first," says Dieckgraefe, an assistant professor of medicine. "But there are two types of immunity, and we're only dealing with half of the immune system. We're priming early immune cells, such as neutrophils and macrophages, not the T cells and B cells that are suppressed by other Crohn's disease therapies."
The strategy appears to help a significant number of patients. In 2002, Korzenik and Dieckgraefe published results from a preliminary15-patient, open-label study in The Lancet reporting that GM-CSF treatment improved symptoms of Crohn's disease in the majority of patients with moderate to severe forms of the disorder.
Following that study, Washington University applied for and received a patent covering the use of colony-stimulating factors for the treatment of Crohn's disease. The technology then was licensed by Washington University to Berlex Laboratories Inc.
In this larger, phase II clinical study, Korzenik, Dieckgraefe and a team of researchers from around the country followed 124 patients at 28 centers to determine whether GM-CSF, commercially known as Leukine® (sagramostim), would help patients with moderate to severe Crohn's disease.
In the study, 81 participants got daily injections of GM-CSF, which stimulates the activity of certain cells in the immune system. Another 43 received an inactive placebo. The investigators wanted to see whether patients on the drug would experience a decrease in the Crohn's Disease Activity Index (CDAI), which registers severity of Crohn's disease symptoms on a scale from one (mild) to 600 (severe).