Steroid-sparing properties of sargramostim in patients with corticosteroid-dependent Crohn's disease: a randomised, double-blind, placebo-controlled, phase 2 study. Issue 10 (7th June 2009)

• Record Type: Journal Article
• Authors: Valentine, J F; Fedorak, R N; Feagan, B; Fredlund, P; Schmitt, R; Ni, P; Humphries, T J
• Is Part Of: Gut. Volume 58:Issue 10(2009)
• Page Start: 1354
• Page End: 1362
• Publication Date: 2009-06-07
• Subjects: Gastroenterology -- Periodicals; 616.33
• DOI: 10.1136/gut.2008.165738
• Languages: English
• ISSNs: 0017-5749

Abstract

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 μg/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 ⩽7.5 mg. The primary endpoint was corticosteroid-free remission (Crohn's Disease Activity Index (CDAI) ⩽150) 4 weeks after corticosteroid elimination. Secondary endpoints were corticosteroid-free response (CDAI decreased by ⩾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. Trial registration number: NCT00206596.