Inflammatory bowel disease

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

J F Valentine¹, R N Fedorak², B Feagan³, P Fredlund⁴, R Schmitt⁵, P Ni⁶, T J Humphries⁶

¹ University of Florida, Gainesville, Florida, USA
² University of Alberta, Edmonton, Canada
³ Robarts Research Institute, University of Western Ontario, London, Canada
⁴ Independent consultant, Seattle, Washington, USA
⁵ Bayer Schering Pharma AG, Berlin, Germany
⁶ Bayer Healthcare Pharmaceuticals, Wayne, New Jersey, USA

^{Correspondence to} Dr J F Valentine, Gastroenterology, Hepatology & Nutrition, University of Florida, 1600 SW Archer Rd, Rm HD 602, Gainesville, FL 32610, USA; John.Valentine{at}medicine.ufl.edu

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.

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