International Journal of Hematology

DOI: 10.1007/s12185-018-2510-7 Pages: 491-498

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

1. Osaka University, Osaka University Hospital, Graduate School of Medicine

2. Tokai University School of Medicine

3. Nippon Medical School, Department of Hematology

4. Juntendo University Shizuoka Hospital

5. Niigata Cancer Center Hospital

6. Keio University Hospital

7. Research & Development, Shire GmbH

8. Global Biometrics, Shire Pharmaceuticals

9. Chiba University Hospital

10. International University of Health and Welfare School of Medicine

Correspondence to:
Yuzuru Kanakura
Tel: +81-6-6879-3870
Email: kanakura@bldon.med.osaka-u.ac.jp

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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.

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