Open-label, dose-titration and continuation study to assess efficacy, safety, and pharmacokinetics of anagrelide in treatment-naïve Japanese patients with essential thrombocythemia

Although anagrelide is widely used for the treatment of essential thrombocythemia (ET) in the USA and Europe, it is not licensed in Japan. Existing literature has reported differences in polymorphism and activity of CYP1A2 in Japanese and non-Japanese ethnic groups, which may alter anagrelide metabolism. We intended to identify the optimum dosage of anagrelide in treatment-naïve Japanese patients with ET and assess its long-term safety and efficacy. Twelve patients with ET and a platelet count of ≥80 × 10⁴/μL were enrolled. Anagrelide was administered at an initial dose of 0.5 mg/day (weeks 1–4), then increased to 1.0 mg/day (weeks 5–8). During the following maintenance (weeks 9–52) and continuation periods (weeks 53–104), the dose was adjusted according to patient safety data and to maintain target platelet counts (<60 × 10⁴/μL). Increasing the dose led to a decrease in mean platelet count, and target platelet counts were maintained in 11 patients. Adverse events were mild or moderate, and none led to discontinuation. This cohort of Japanese patients exhibited higher pharmacokinetic exposures of anagrelide and its active metabolite than those previously documented in non-Japanese patients. These differences were modest, suggesting specific dosing regimens for Japanese patients are not required.