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;
- Revised 31 March 2009
- Accepted 28 April 2009
- Published Online First 7 June 2009
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.
Funding This trial (and editorial assistance provided by Adelphi toward the preparation of this paper) was funded by Bayer HealthCare Pharmaceuticals.
Competing interests Declared (the declaration can be viewed on the Gut website at http://www.gut.bmj.com/supplemental).
Provenance and Peer review Not commissioned; externally peer reviewed.
Ethics approval The study was approved by the institutional review boards at each of the participating sites.