Korzenik JR et al. (2005) Sargramostim for active Crohn's disease. N Engl J Med 352: 2193–2201

It has been suggested that Crohn's disease might be the result of an inherent defect of the intestinal immune system, and thus stimulation, rather than suppression, could be an alternative therapeutic option. Sargramostim, a yeast-derived granulocyte-macrophage colony-stimulating factor, may help to maintain and enhance the intestinal innate immune system and thus decrease inflammation.

A randomized, placebo-controlled trial was carried out in adults with moderate-to-severe Crohn's disease, defined as a Crohn's Disease Activity Index score of 220–475. A total of 124 patients were randomly allocated in a 2:1 ratio to receive sargramostim (6 μg/kg body weight) or placebo, administered daily by subcutaneous injection, for 56 days. The primary endpoint of the study was a decrease of at least 70 points from baseline in the Crohn's Disease Activity Index score; secondary endpoints included a decrease of 100 points, remission, and an increase in health-related quality of life.

There was no significant difference between the two groups in terms of primary outcome; however, significantly more patients in the sargramostim group had reached the secondary endpoints of a decrease of 100 points or remission by day 57 compared with placebo. In addition, at 30 days post-treatment, sargramostim patients had higher response and remission rates, and significantly greater improvements in health-related quality of life at all evaluation points of the study.

Korzenik and colleagues conclude that, despite a negative finding with regard to the primary endpoint, secondary endpoints suggest a beneficial role for sargramostim in Crohn's disease in terms of severity of symptoms and quality of life, and propose that “...a treatment designed to modulate intestinal innate immune defense may have a role in patients with Crohn's disease”. However, they stress that the role of granulocyte-macrophage colony-stimulating factors in Crohn's disease remains to be defined.