Treatment with a recombinant form of a hematopoietic growth factor GM-CSF, Sargramostim ( Leukine ), significantly reduced symptom severity and improved quality of life after 56 days of daily drug injections in patients with active Crohn's disease.
The finding supports a new concept that Crohn's, rather than being caused primarily by an excessive immune response, could actually result from defects in the body's first line of immune defense.
" We've proposed that the inflammation that occurs with Crohn's is actually secondary to an earlier problem," says Joshua Korzenik, MD, co-director of the Crohn's and Colitis Center at Massachusetts General Hospital ( MGH ), lead author of the study. " We believe there is a defect with the gastrointestinal innate immune system, a group of cells that stop any microbes from entering the body. If normal intestinal bacteria are not controlled by the innate immune system, a compensatory secondary inflammation could produce the symptoms of Crohn's."
Crohn's disease is a chronic inflammatory bowel disease, usually affects the small intestine, causing abdominal pain and chronic diarrhea.
Serious symptoms can include ulceration, bleeding, the development of fistulas - openings from affected areas into other organs - or intestinal blockage.
About half a million people in the U.S.are affected by Crohn's.
Current treatments are designed to reduce symptoms, and the disorder often enters periods of remission, some lengthy, before recurring.
Korzenik and Dieckgraefe, at Washington University School of Medicine in St. Louis, developed their hypothesis based on studies of certain genetic disorders known to affect the innate immune system.
Because some of these disorders include symptoms virtually identical to those of Crohn's, they wondered if a similar process was occurring in Crohn's patients, with the excessive inflammatory response actually resulting from an unsuspected defect in innate immunity.
To test this concept, they conducted a pilot study of treatment with GM-CSF, which stimulates the innate immune system and is usually used to restore bone marrow function in chemotherapy patients.
Promising results from that study, published in 2002, led to the current multicenter investigation.
Patients with moderate to severe Crohn's disease enrolled in the study at 28 centers across the U.S.
Of the 94 participants who completed the 56-day treatment cycle, 57 received daily injections of GM-CSF, while 37 received placebo injections.
Participants were evaluated every two weeks during the study period and 30 days after treatment concluded.
Based on a standard index of Crohn's disease symptoms, significantly more participants receiving GM-CSF were judged to have major improvement or remission of their symptoms than were those receiving placebo injections.
Source: Massachusetts General Hospital, 2005