Steroid-sparing properties of sargramostim in patients with corticosteroid-dependent Crohn's disease: a randomised, double-blind, placebo-controlled, phase 2 study.

Abstract

OBJECTIVE:

Although treatment with corticosteroids induces remission in Crohn's disease, prolonged exposure to corticosteroids is undesirable. This randomised clinical trial evaluated the efficacy of recombinant human granulocyte-macrophage colony-stimulating factor (sargramostim), an activator of innate immunity, in corticosteroid-dependent patients with Crohn's disease.

DESIGN:

Patients were randomised in a 2:1 ratio, to sargramostim 6 microg/kg subcutaneously once daily or placebo for up to 22 weeks. The study consisted of (1) an adjunctive phase (weeks 1-4) in which patients received study drug plus corticosteroid therapy; (2) a forced corticosteroid tapering phase (weeks 4-14); and (3) an observation phase (4 weeks) in which patients received study drug plus prednisone < or =7.5 mg. The primary endpoint was corticosteroid-free remission (Crohn's Disease Activity Index (CDAI) < or =150) 4 weeks after corticosteroid elimination. Secondary endpoints were corticosteroid-free response (CDAI decreased by > or =100) and induction of remission in patients who reduced the dose of corticosteroid to 2.5-7.5 mg.

RESULTS:

Eighty-seven patients were randomised to sargramostim and 42 to placebo. Significantly more sargramostim-treated patients than placebo patients achieved corticosteroid-free remission (18.6% vs 4.9%; p = 0.03). Similar differences were seen for corticosteroid-free response and in patients who tapered corticosteroids to 2.5-7.5 mg/day. Sargramostim treatment was also associated with significant improvements in health-related quality of life. Patients who received sargramostim were more likely to experience musculoskeletal pain, injection site reactions and dyspnoea.

CONCLUSIONS:

Sargramostim was more effective than placebo for inducing corticosteroid-free remission in patients with Crohn's disease with corticosteroid dependence. Sargramostim may provide significant benefit in this population if these findings are confirmed.

• Authors: J F Valentine, R N Fedorak, B Feagan, P Fredlund, R Schmitt, P Ni, T J Humphries
• Journal: Gut (Gut) Vol. 58 Issue 10 Pg. 1354-62 (Oct 2009) ISSN: 1468-3288 [Electronic] England
• PMID: 19505878 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Adrenal Cortex Hormones
• Gastrointestinal Agents
• Recombinant Proteins
• sargramostim
• Granulocyte-Macrophage Colony-Stimulating Factor

Topics

• Adrenal Cortex Hormones (administration & dosage, adverse effects)
• Adult
• Aged
• Crohn Disease (drug therapy, psychology)
• Double-Blind Method
• Drug Administration Schedule
• Female
• Gastrointestinal Agents (administration & dosage, adverse effects)
• Granulocyte-Macrophage Colony-Stimulating Factor (administration & dosage, adverse effects)
• Humans
• Male
• Middle Aged
• Quality of Life (psychology)
• Recombinant Proteins
• Remission Induction
• Treatment Outcome
• Young Adult