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Steroid-sparing Properties of Sargramostim in Patients With Corticosteroid-dependent Crohn’s disease: A Randomised, Double-blind, Placebo-controlled, Phase 2 Study
  1. John F Valentine (valenjf{at}medicine.ufl.edu)
  1. University of Florida, United States
    1. Richard N Fedorak
    1. University of Alberta, Canada
      1. Brian Feagan
      1. University of Western Ontario, Canada
        1. Paul Fredlund
        1. Independent Consultant, Seattle, WA, United States
          1. Ruediger Schmitt
          1. Bayer Schering Pharma AG, Germany
            1. Pingping Ni
            1. Bayer Healthcare Pharmaceuticals, Inc, United States
              1. Thomas J Humphries
              1. Bayer Healthcare Pharmaceuticals, Inc, United States

                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 Crohn’s disease patients with corticosteroid dependence. Sargramostim may provide significant benefit in this population if these findings are confirmed.

                ClinicalTrials.gov Identifier: NCT00206596.

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