Sargramostim in patients with Crohn’s disease: results of a phase 1–2 study

  • Masakazu Takazoe
  • Toshiyuki Matsui
  • Satoshi Motoya
  • Takayuki Matsumoto
  • Toshifumi Hibi
  • Mamoru Watanabe
Original Article—Alimentary Tract



We aimed to assess the tolerability, pharmacokinetics, safety, and efficacy of sargramostim in Japanese patients with active Crohn’s disease (CD).


Patients with moderately to severely active CD were enrolled. Step 1 was an open-label, phase 1 study of 2 μg/kg per day sargramostim administered subcutaneously (SC) for 4 weeks, with an optional 8-week extension with 6 μg/kg per day. Step 2 was an open-label, phase 1–2 study of the tolerability and pharmacokinetics of SC sargramostim 6 μg/kg per day over 4 weeks and of 8-week efficacy and safety. Efficacy variables were the proportion of patients achieving a clinical response [≥100-point decrease from baseline in the CD activity index (CDAI)] and the proportion achieving clinical remission (CDAI ≤ 150 points).


Six patients participated in Step 1; five in Step 2. Serum concentrations of sargramostim peaked within 1 h of administration; mean terminal half-life was 2 h. Maximal serum concentrations increased with the dose. Mean accumulation ratios were 0.998 in Step 1 and 0.673 in Step 2. One of the six patients in the Step-1 extension and none of the five in Step 2 achieved a clinical response. Clinical remission was reported in one patient in each step. A notable decrease in median CDAI scores was observed in the extension and Step 2. In responders, improvement tended to be maintained through the 30-day follow-up. Drug-related adverse events included injection-site reaction, pyrexia, back pain, and bone pain.


The systemic exposure of sargramostim increased dose-dependently. No accumulation in systemic exposure was associated with the repeated once-daily administration. SC sargramostim at 6 μg/kg per day improved median CDAI scores. A minority of patients experienced clinical remission or clinical response.


Crohn’s disease activity index (CDAI) Crohn’s disease Inflammatory bowel disease Sargramostim 



We thank the members of the NOVEL 9 Study Group. Medical writing assistance and editorial support were provided by Adelphi Inc. and were funded by Bayer Yakuhin Ltd.


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Copyright information

© Springer 2009

Authors and Affiliations

  • Masakazu Takazoe
    • 1
  • Toshiyuki Matsui
    • 2
  • Satoshi Motoya
    • 3
  • Takayuki Matsumoto
    • 4
  • Toshifumi Hibi
    • 5
  • Mamoru Watanabe
    • 6
  1. 1.Department of Internal MedicineSocial Insurance Central General HospitalTokyoJapan
  2. 2.Fukuoka University Chikushi HospitalChikushinoJapan
  3. 3.Department of Digestive Organs ISapporo-kosei General HospitalSapporoJapan
  4. 4.Department of Lower GastroenterologyHyogo College of MedicineNishinomiyaJapan
  5. 5.Division of Gastroenterology, Department of Internal MedicineKeio University School of MedicineTokyoJapan
  6. 6.Department of Gastroenterology and HepatologyTokyo Medical and Dental UniversityTokyoJapan

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