HONOLULU — Sargramostim shows considerable promise as a novel treatment for Crohn's disease, Dr. Suzanne Laplante reported at the annual meeting of the American College of Gastroenterology.
She reported on 124 patients with moderate to severe Crohn's disease who participated in the phase II New Opportunities to Verify Evolving Logic in Crohn's Disease (NOVEL) trial. They were randomized 2:1 to sargramostim (Leukine)—a granulocyte-macrophage, colony-stimulating factor—at 6 mcg/kg per day subcutaneously, or to placebo for 8 weeks. All patients also received background antibiotics and/or 5-aminosalicylic acid compounds as needed.
Sargramostim resulted in a significant reduction in disease severity. The remission rate at 8 weeks was 40% in the sargramostim group and 19% in the placebo group. The clinical response rate, as defined by at least a 100-point drop from baseline in the Crohn's Disease Activity Index, was 48% with sargramostim and 26% with placebo, said Dr. Laplante of Schering AG Germany in Berlin.
But her main focus was on the drug's impact on quality of life, increasingly seen as a major clinical end point in the management of chronic incurable diseases such as Crohn's disease, heart failure, and arthritis.
Clinically meaningful quality-of-life improvements were noted in the Inflammatory Bowel Disease Questionnaire (IBDQ) as early as day 29 in the sargramostim group. At 30 days after the conclusion of treatment, patients in the sargramostim group averaged a 20% improvement over baseline in their IBDQ scores, compared with a 7% gain in the placebo arm. Patients in the sargramostim group had moderate to large improvements in three of the four IBDQ subscales—social function, bowel symptoms, and systemic symptoms—with only the emotional subscale showing no significant change.
Quality of life was also measured by the Short Form-36 Health Survey. Moderate to large improvements in the general health, bodily pain, social function, vitality, and physical component summary scores were observed in the sargramostim group as early as day 15.
Sargramostim is classified as a biologic response modifier. Its FDA-approved indications are to accelerate recovery of white blood cells after chemotherapy and in conjunction with bone marrow or stem cell transplantation. Recent evidence that Crohn's disease results from impairments in innate immunity provided the rationale for developing sargramostim through the NOVEL clinical trials program as an alternative to antibiotics, corticosteroids, immunosuppressants, and tumor necrosis factor-α inhibitors.
Sargramostim activates intestinal immune defenses. The biologic response modifier promotes production of cytokines, including tumor necrosis factor-? and interleukin-1. Those cytokines are thought to play an important role in regulating intestinal inflammation secondary to the defects in mucosal epithelial barrier function that are believed to figure centrally in Crohn's disease, Dr. Laplante said.