COPENHAGEN — Daily treatment with sargramostim led to significantly improved quality of life in patients with moderate to severe Crohn's disease in a study with 124 patients.
“In addition to reducing disease severity scores, sargramostim appears to significantly improve quality of life,” as measured with both the Inflammatory Bowel Disease Questionnaire (IBDQ) and the Short Form-36, Joshua R. Korzenik, M.D., said at the 13th United European Gastroenterology Week.
Treatment with sargramostim, a yeast-derived, recombinant human granulocyte-macrophage colony-stimulating factor, is a striking departure from therapy with the immunosuppressive agents usually used to treat Crohn's disease.
The rationale is that sargramostim may help maintain the innate intestinal immune barrier and may also augment host defenses and reduce the inflammation associated with Crohn's.
The main efficacy end point of the study was a change in disease severity as measured with the Crohn's Disease Activity Index (CDAI) score.
A report published last May by Dr. Korzenik and his associates said that daily treatment with 6 mcg/kg sargramostim administered by subcutaneous injection failed to achieve the study's primary end point, a 70-point or greater drop in the score after 57 days of treatment. The 54% rate of this response with sargramostim wasn't significantly better than the 44% rate in the placebo group.
But sargramostim treatment did achieve two secondary end points: It produced a significant increase in clinical response, defined as a 100-point or greater decline in the CDAI score by day 57. By this measure, responses occurred in 48% of the sargramostim-treated patients, compared with 26% in the control arm. The drug also produced more remissions at day 57, defined as a CDAI score of 150 points or less, the researchers reported (N. Engl. J. Med. 2005;352:2193–201).
Remissions occurred in 40% of the sargramostim patients and 19% of the placebo group.
The study was sponsored by Berlex, which markets sargramostim (Leukine). The drug has several approved indications in the United States: following induction chemotherapy in patients with acute myelogenous leukemia; before and after transplantation of autologous peripheral blood progenitor cells; for myeloid reconstitution after autologous or allogenic bone marrow transplantation; and for bone marrow transplant failure or engraftment delay.
Dr. Korzenik has been a consultant to and lecturer for Berlex and for several other companies. He is codirector of the Massachusetts General Hospital Crohn's and Colitis Center, Boston.
In the new quality of life analysis, IBDQ scores were significantly better in the sargramostim group than in the placebo group by 29 days after the start of treatment, and this advantage was maintained throughout the 57-day treatment period and out to 30 days following the end of treatment. After 57 days, the IBDQ scores, which measure quality of life, had risen by a mean of 15% in the placebo group and 24% in patients taking sargramostim.
Sargramostim treatment also produced notable improvements in vitality and social subscores, suggesting that the treatment increased energy for everyday activities. The vitality subscore of the SF-36 increased by 68% over baseline by day 57. The social subscore of the IBDQ improved by an average of 14% when measured 30 days after stopping treatment, compared with a 4% increase in the placebo group. The social score of the SF-36 improved by 25% in the sargramostim group.
Drug treatment also led to improvements in systemic pain and bowel symptom scores, variables of great concern to patients with Crohn's disease, he added. Bowel symptoms decreased by 23%–33%. The degree of improvement varied depending on when measurements were made during the study. Systemic pain scores had decreased 39% after 57 days of treatment and 45% at 30 days after treatment ended.