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International Journal of Hematology

, Volume 108, Issue 5, pp 491–498 | Cite as

A phase 3b, multicenter, open-label extension study of the long-term safety of anagrelide in Japanese adults with essential thrombocythemia

  • Yuzuru Kanakura
  • Yukari Shirasugi
  • Hiroki Yamaguchi
  • Michiaki Koike
  • Takaaki Chou
  • Shinichiro Okamoto
  • Heinrich Achenbach
  • Jingyang Wu
  • Chiaki Nakaseko
Original Article
  • 220 Downloads

Abstract

Cytoreductive therapy is used in high-risk essential thrombocythemia (ET) to reduce risk of thrombohemorrhagic complications. Anagrelide is an orally active, quinazolone-derived platelet-lowering agent approved for first-line treatment of high-risk ET in Japan. Long-term safety and efficacy data were collected from 53 Japanese high-risk ET patients (Study 308); 41 patients who completed Study 308 entered this phase 3b, open-label extension (Study 309; NCT01467661). Reductions in mean platelet counts occurred throughout the study, from 1021.6 × 109/L (at Study 308 baseline) to 675.4 × 109/L at final assessment. At month 48 (since Study 308 enrollment), mean platelet count was 444.5 × 109/L in the 10 patients who completed 4 years of therapy. Overall, platelet counts decreased from 1088.3 × 109/L at Study 308 baseline (n = 33) to 473.5 × 109/L at final assessment (n = 31). Long-term platelet count reductions were maintained without marked changes in mean anagrelide dose. Anagrelide was generally well tolerated, with anemia (54.7%) and headache (49.1%) as the most frequent adverse events. These findings indicate that anagrelide effectively reduces platelet counts in high-risk Japanese ET patients, with titration resulting in a well-tolerated, effective and sustainable dose. In conclusion, these results support anagrelide administration to high-risk Japanese ET patients using individualized dosing strategies defined in instructions previously approved in Europe and the USA.

Keywords

Anagrelide Essential thrombocythemia Japan 

Notes

Acknowledgements

The authors thank the patients and acknowledge the contribution of all investigators who participated in this study. The study was sponsored by Shire Pharmaceutical Development Ltd, Basingstoke, UK. Under the direction of the authors, Peter Birch and Rachel Brown of ACUMED, an Ashfield business, part of UDG Healthcare plc, provided writing and editorial assistance funded by Shire. All authors reviewed the manuscript drafts and approved the submission for publication.

Compliance with ethical standards

Conflict of interest

Yuzuru Kanakura: grants from Kyowa Hakko Kirin, Shionogi, Chugai Pharmaceutical, Pfizer, Eisai, Astellas, Nippon Shinyaku, Alexionpharma, Bristol-Myers Squibb, Toyama Chemical, and Fujimotoseiyaku. Yukari Shirasugi: honoraria from Novartis. Hiroki Yamaguchi: none. Michiaki Koike: none. Takaaki Chou: honoraria from Celgene, Novartis, Takeda, Bristol-Myers Squibb. Shinichiro Okamoto: none. Henri Achenbach: employed by Shire, stock or other interests in Shire. Jingyang Wu: employed by Shire, stock or other interests in Shire. Chiaki Nakaseko: none.

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Copyright information

© The Japanese Society of Hematology 2018

Authors and Affiliations

  • Yuzuru Kanakura
    • 1
  • Yukari Shirasugi
    • 2
  • Hiroki Yamaguchi
    • 3
  • Michiaki Koike
    • 4
  • Takaaki Chou
    • 5
  • Shinichiro Okamoto
    • 6
  • Heinrich Achenbach
    • 7
  • Jingyang Wu
    • 8
  • Chiaki Nakaseko
    • 9
    • 10
  1. 1.Graduate School of MedicineOsaka University, Osaka University HospitalSuitaJapan
  2. 2.Tokai University School of MedicineIseharaJapan
  3. 3.Department of HematologyNippon Medical SchoolTokyoJapan
  4. 4.Juntendo University Shizuoka HospitalShizuokaJapan
  5. 5.Niigata Cancer Center HospitalNiigataJapan
  6. 6.Keio University HospitalTokyoJapan
  7. 7.Research & Development, Shire GmbHZugSwitzerland
  8. 8.Global Biometrics, Shire PharmaceuticalsLexingtonUSA
  9. 9.Chiba University HospitalChibaJapan
  10. 10.International University of Health and Welfare School of MedicineNaritaJapan

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