Steroid-sparing properties of sargramostim in patients with corticosteroid-dependent Crohn’s disease: a randomised, double-blind, placebo-controlled, phase 2 study
- 1University of Florida, Gainesville, Florida, USA
- 2University of Alberta, Edmonton, Canada
- 3Robarts Research Institute, University of Western Ontario, London, Canada
- 4Independent consultant, Seattle, Washington, USA
- 5Bayer Schering Pharma AG, Berlin, Germany
- 6Bayer 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
- Revised 31 March 2009
- Accepted 28 April 2009
- Published Online First 7 June 2009
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.
Footnotes
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Funding This trial (and editorial assistance provided by Adelphi toward the preparation of this paper) was funded by Bayer HealthCare Pharmaceuticals.
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Competing interests Declared (the declaration can be viewed on the Gut website at http://www.gut.bmj.com/supplemental).
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Provenance and Peer review Not commissioned; externally peer reviewed.
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Ethics approval The study was approved by the institutional review boards at each of the participating sites.
