International Journal of Hematology

, Volume 96, Issue 1, pp 26–33 | Cite as

Evaluation of bleeding-related episodes in patients with immune thrombocytopenia (ITP) receiving romiplostim or medical standard of care

  • Roberto Stasi
  • Magaral Murali
  • Marc Michel
  • Jean-François Viallard
  • Aristoteles Giagounidis
  • Ann Janssens
  • Jason Legg
  • Robert Deuson
  • Mark D. Danese
Original Article

Abstract

Romiplostim increases platelet counts and reduces the risk of bleeding in patients with immune thrombocytopenia (ITP). This post hoc analysis compared the effect of romiplostim versus medical standard of care (SOC) on clinically relevant bleeding-related episodes (BREs) in a 52-week open-label study of patients with ITP. BREs were defined as actual bleeding events and/or use of rescue medication. Nonsplenectomized adult patients with ITP were randomized to receive weekly subcutaneous injections of romiplostim (n = 157) or SOC (n = 77). The rate of all BREs (per 100 patient-weeks) was lower in patients treated with romiplostim (3.1) than in those treated with SOC (9.4); the relative rate (romiplostim/SOC) was 0.33 (95 % CI 0.27–0.40). The rate of BREs associated with immunoglobulin (Ig) rescue medication was also lower for romiplostim (0.2) than SOC (4.8); the relative rate (romiplostim/SOC) was 0.05 (95 % CI 0.03–0.08). BRE rates were lower in patients with platelet counts ≥50 × 109/L, and patients treated with romiplostim spent more time with platelet counts ≥50 × 109/L than did patients treated with SOC. Bleeding-related hospitalizations were rare in both groups. Thus, romiplostim treatment provided greater reductions in all BREs, as well as BREs involving Ig rescue medications, than did SOC.

Keywords

Thrombocytopenia Bleeding Platelets Thrombopoietin 

Notes

Acknowledgments

In collaboration with the investigators, Amgen Inc. designed the study, conducted statistical analyses, and interpreted the data, which Amgen Inc. holds. Each author participated in either the design or execution of the study, contributed to the interpretation of the study results, provided critical input during the manuscript review process, approved the final version of the manuscript, and took responsibility for the content of the manuscript. The authors had unrestricted access to the primary data and were not limited by Amgen Inc. in the writing of this article. Professional writing assistance was provided by Amy Lindsay PhD, who was funded by Amgen Inc, and Michelle Zakson, an employee of Amgen Inc. The authors thank the study coordinators, nurses, and patients who participated in the study.

Conflict of interest

This research was funded by Amgen Inc., Thousand Oaks, CA. Dr. Stasi has served as a consultant for Amgen, GlaxoSmithKline, and Suppremol and has participated on advisory boards and/or as a speaker at medical education events supported by Amgen, GlaxoSmithKline, Nycomed, Novo, Bayer, and Baxter. Dr Viallard is a consultant for Amgen and GSK, and has participated on advisory board and/or as a speaker at medical education events supported by Amgen or GSK. Dr. Marc Michel served as a consultant for Amgen, GlaxoSmithKline, and Suppremol and has participated on advisory boards and/or as a speaker at medical education events supported by Amgen, GlaxoSmithKline and Roche Drs Deuson and Legg are employees of Amgen, Inc. Dr. Danese is a paid consultant for Amgen, Inc.

References

  1. 1.
    Cines DB, Bussel JB, Liebman HA, Luning Prak ET. The ITP syndrome: pathogenic and clinical diversity. Blood. 2009;113:6511–21.PubMedCrossRefGoogle Scholar
  2. 2.
    Tarantino M, Sunkara U, George JN, Aledort LM, Guo M, Berger D, et al. Evaluation of bleeding and thrombotic events during long-term use of romiplostim in patients with chronic immune thrombocytopenic purpura. Blood. 2008;112:3422. (ASH Annual Meeting Abstracts).Google Scholar
  3. 3.
    Bussel JB, Provan D, Shamsi T, Cheng G, Psaila B, Kovaleva L, et al. Effect of eltrombopag on platelet counts and bleeding during treatment of chronic idiopathic thrombocytopenic purpura: a randomised, double-blind, placebo-controlled trial. Lancet. 2009;373:641–8.PubMedCrossRefGoogle Scholar
  4. 4.
    Kuter DJ, Bussel JB, Lyons RM, Pullarkat V, Gernsheimer TB, Senecal FM, et al. Efficacy of romiplostim in patients with chronic immune thrombocytopenic purpura: a double-blind randomised controlled trial. Lancet. 2008;371:395–403.PubMedCrossRefGoogle Scholar
  5. 5.
    Kuter DJ, Bussel J, Newland A, Wasser JS, Lyons RM, George JN, et al. Long-term efficacy and safety of romiplostim treatment of adult patients with chronic immune thrombocytopenia (ITP): final report from an open-label extension study. Blood 2010;116 (ASH Annual Meeting Abstracts).Google Scholar
  6. 6.
    Bussel JB, Kuter DJ, Pullarkat V, Lyons RM, Guo M, Nichol JL. Safety and efficacy of long-term treatment with romiplostim in thrombocytopenic patients with chronic ITP. Blood. 2009;113:2161–71.PubMedCrossRefGoogle Scholar
  7. 7.
    Kuter DJ, Rummel M, Boccia R, Macik BG, Pabinger I, Selleslag D, et al. Romiplostim or standard of care in patients with immune thrombocytopenia. N Engl J Med. 2010;363:1889–99.PubMedCrossRefGoogle Scholar
  8. 8.
    George JN, Woolf SH, Raskob GE, Wasser JS, Aledort LM, Ballem PJ, et al. Idiopathic thrombocytopenic purpura: a practice guideline developed by explicit methods for the American Society of Hematology. Blood. 1996;88:3–40.PubMedGoogle Scholar
  9. 9.
    Neunert C, Lim W, Crowther M, Cohen A, Solberg L Jr, Crowther MA. The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood. 2011;117:4190–207.PubMedCrossRefGoogle Scholar
  10. 10.
    Provan D, Stasi R, Newland AC, Blanchette VS, Bolton-Maggs P, Bussel JB, et al. International consensus report on the investigation and management of primary immune thrombocytopenia. Blood. 2010;115:168–86.PubMedCrossRefGoogle Scholar
  11. 11.
    Schiavotto C, Ruggeri M, Rodeghiero F. Adverse reactions after high-dose intravenous immunoglobulin: incidence in 83 patients treated for idiopathic thrombocytopenic purpura (ITP) and review of the literature. Haematologica. 1993;78:35–40.PubMedGoogle Scholar
  12. 12.
    George JN, Mathias SD, Go RS, Guo M, Henry DH, Lyons R, et al. Improved quality of life for romiplostim-treated patients with chronic immune thrombocytopenic purpura: results from two randomized, placebo-controlled trials. Br J Haematol. 2009;144:409–15.PubMedCrossRefGoogle Scholar
  13. 13.
    Gernsheimer TB, George JN, Aledort LM, Tarantino MD, Sunkara U, Matthew Guo D, et al. Evaluation of bleeding and thrombotic events during long-term use of romiplostim in patients with chronic immune thrombocytopenia (ITP). J Thromb Haemost. 2010;8:1372–82.PubMedCrossRefGoogle Scholar
  14. 14.
    Michel M, Rauzy OB, Thoraval FR, Languille L, Khellaf M, Bierling P, et al. Characteristics and outcome of immune thrombocytopenia in elderly: results from a single center case-controlled study. Am J Hematol. 2011;86:980–4.PubMedCrossRefGoogle Scholar

Copyright information

© The Japanese Society of Hematology 2012

Authors and Affiliations

  • Roberto Stasi
    • 1
  • Magaral Murali
    • 2
  • Marc Michel
    • 3
  • Jean-François Viallard
    • 4
    • 5
  • Aristoteles Giagounidis
    • 6
  • Ann Janssens
    • 7
  • Jason Legg
    • 8
  • Robert Deuson
    • 8
  • Mark D. Danese
    • 9
  1. 1.Department of HaematologySt. George’s HospitalLondonUK
  2. 2.Central Indiana Cancer CenterIndianapolisUSA
  3. 3.CHU Hôpital Henri Mondor, Assistance Publique Hopitaux de ParisUniversité Paris-Est CreteilCréteil CedexFrance
  4. 4.Hôpital Haut LévêquePessac CedexFrance
  5. 5.University Victor SegalenBordeaux 2France
  6. 6.St. Johannes HospitalDuisburgGermany
  7. 7.Universitair Ziekenhuis GasthuisbergLeuvenBelgium
  8. 8.Amgen Inc.Thousand OaksUSA
  9. 9.Outcomes Insights Inc.Westlake VillageUSA

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