Immune-Enhancer GM-CSF Helpful in Crohn's Disease

Laurie Barclay, MD

November 08, 2002

Nov. 8, 2002 — The immune enhancer granulocyte-macrophage colony stimulating factor (GM-CSF) sagramostim significantly improved symptoms in 80% of 15 patients with moderate to severe Crohn's disease and induced clinical remission in more than 50%, according to a research letter in the Nov. 9 issue of The Lancet. Symptoms recurred with discontinuation of the drug, also known by the trade name Leukine, but then resolved with reinstitution of therapy.

"At first blush, the idea of priming the immune system in patients with Crohn's disease sounds sort of like throwing oil on a fire," senior author Joshua R. Korzenik, MD, from Washington University School of Medicine in St. Louis, Missouri, says in a news release. "You might compare it to proposing a high cholesterol diet to treat heart disease."

Despite the apparent paradox of treating an autoimmune disorder with an immune stimulant, Dr. Korzenik and first author Brian K. Dieckgraefe, MD, PhD, noted that several genetic disorders of immunity were associated with Crohn's-like gastrointestinal problems, notably glycogen storage disease 1B and chronic granulomatous disease. They therefore tested GM-CSF in an open-label trial in 15 patients with moderate to severe Crohn's disease.

"Conventional thinking would have predicted that these drugs could worsen the disease," Dr. Dieckgraefe says. "But we thought that these immune deficiencies provided a good model for how our Crohn's patients would respond. Furthermore, we knew that GM-CSF was a natural protein that already was present in the body."

Of the 15 patients who received daily injections of GM-CSF for eight weeks, 12 (80%) improved significantly during the study, and eight (53%) achieved clinical remission after treatment. Mean Crohn's disease activity index (CDAI) score fell by 190 points (P<.0001), and average Inflammatory Bowel Disease Questionnaire (IBDQ) score increased from 108 to 179, reflecting significant improvements in quality of life.

Ongoing follow-up revealed recurrence when GM-CSF was withdrawn, and improvement when it was reinstituted.

"The results of this open-label trial make us optimistic that this approach may someday help large numbers of patients who don't respond to traditional Crohn's disease therapy," Dr. Korzenik says. "However, we need to test our findings in a larger, randomized, placebo-controlled trial."

Washington University applied for a patent covering the use of colony-stimulating factors for the treatment of Crohn's disease, and then licensed the technology to Berlex, which has begun a large-scale, multicenter trial of Leukine. The Department of Medicine and both authors are entitled to a share of the royalties received by the University from the licensed technology.

Lancet. 2002;360:1478-1479

Reviewed by Gary D. Vogin, MD


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.