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

Research output: Contribution to journalArticle

1 Citation (Scopus)

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.

Original languageEnglish
JournalInternational Journal of Hematology
DOIs
Publication statusAccepted/In press - 2018 Jan 1

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Essential Thrombocythemia
Platelet Count
Safety
Headache
anagrelide
Anemia
Japan
Therapeutics
Blood Platelets

Keywords

  • Anagrelide
  • Essential thrombocythemia
  • Japan

ASJC Scopus subject areas

  • Hematology

Cite this

A phase 3b, multicenter, open-label extension study of the long-term safety of anagrelide in Japanese adults with essential thrombocythemia. / Kanakura, Yuzuru; Shirasugi, Yukari; Yamaguchi, Hiroki; Koike, Michiaki; Chou, Takaaki; Okamoto, Shinichiro; Achenbach, Heinrich; Wu, Jingyang; Nakaseko, Chiaki.

In: International Journal of Hematology, 01.01.2018.

Research output: Contribution to journalArticle

Kanakura, Yuzuru ; Shirasugi, Yukari ; Yamaguchi, Hiroki ; Koike, Michiaki ; Chou, Takaaki ; Okamoto, Shinichiro ; Achenbach, Heinrich ; Wu, Jingyang ; Nakaseko, Chiaki. / A phase 3b, multicenter, open-label extension study of the long-term safety of anagrelide in Japanese adults with essential thrombocythemia. In: International Journal of Hematology. 2018.
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AU - Koike, Michiaki

AU - Chou, Takaaki

AU - Okamoto, Shinichiro

AU - Achenbach, Heinrich

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