title: A lower starting dose of eltrombopag is efficacious in Japanese patients with previously treated chronic immune thrombocytopenia.
abstract: BACKGROUND
  Eltrombopag is an oral, non-peptide thrombopoietin receptor agonist that has shown efficacy and safety in chronic immune thrombocytopenia (ITP). However, ethnic differences in eltrombopag exposure have been reported: area under the curve exposure to eltrombopag was 87% greater among ITP patients of East Asian descent than among ITP patients of non-East Asian ITP descent.
  
  
  OBJECTIVE
  To evaluate the efficacy and safety of eltrombopag by using, in Japanese ITP patients, lower starting (12.5 mg) and maximum (50 mg) doses of eltrombopag than the standard starting (50 mg) and maximum (75 mg) doses approved in the USA and Europe.
  
  
  METHODS
  We examined 23 Japanese patients with previously treated chronic ITP with a platelet count of < 30,000 μL(-1) in a multicenter study comprising a randomized, double-blind, placebo-controlled phase for 6-week evaluation (15 eltrombopag, and eight placebo) and an open-label phase for 6-month evaluation (23 eltrombopag).
  
  
  CONCLUSIONS
  The response rate (platelet count of ≥ 50,000 μL(-1) ) at week 6 of the 6-week double-blind phase was 60% in eltrombopag-treated patients and 0% in placebo-treated patients. Ten of 23 patients (43.5%) responded for ≥ 75% of predefined assessment visits during the 6-month open-label phase. Notably, 22% (5/23) of patients responded to 12.5 mg of eltrombopag, which was administered within the first 3 weeks of eltrombopag treatment. Bleeding decreased with eltrombopag treatment as compared with baseline. Eltrombopag was generally well tolerated; one patient experienced a transient ischemic attack on day 9. Eltrombopag (12.5-50 mg) is effective for the management of Japanese patients with chronic ITP (NCT00540423).
authors.affiliation: Osaka University Hospital, Suita, Osaka, Japan. yoshi@hp-blood.med.osaka-u.ac.jp
authors.forename: Y
authors.initials: Y
authors.lastname: Tomiyama
authors.forename: Y
authors.initials: Y
authors.lastname: Miyakawa
authors.forename: S
authors.initials: S
authors.lastname: Okamoto
authors.forename: S
authors.initials: S
authors.lastname: Katsutani
authors.forename: A
authors.initials: A
authors.lastname: Kimura
authors.forename: Y
authors.initials: Y
authors.lastname: Okoshi
authors.forename: H
authors.initials: H
authors.lastname: Ninomiya
authors.forename: H
authors.initials: H
authors.lastname: Kosugi
authors.forename: S
authors.initials: S
authors.lastname: Nomura
authors.forename: K
authors.initials: K
authors.lastname: Ozaki
authors.forename: Y
authors.initials: Y
authors.lastname: Ikeda
authors.forename: T
authors.initials: T
authors.lastname: Hattori
authors.forename: K
authors.initials: K
authors.lastname: Katsura
authors.forename: Y
authors.initials: Y
authors.lastname: Kanakura
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D044466:Asian People; D001565:Benzoates / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D001792:Blood Platelets / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D002908:Chronic Disease; D004311:Double-Blind Method; D005260:Female; D006401:Hematologic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D006470:Hemorrhage / Q000097:blood / Q000208:ethnology / Q000276:immunology / Q000517:prevention & control*; D006801:Humans; D006834:Hydrazines / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D010919:Placebos; D010976:Platelet Count; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000097:blood / Q000188:drug therapy* / Q000208:ethnology / Q000276:immunology; D011720:Pyrazoles / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D053628:Receptors, Thrombopoietin / Q000819:agonists / Q000097:blood; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D001565:Benzoates; D006401:Hematologic Agents; D006834:Hydrazines; D010919:Placebos; D011720:Pyrazoles; D053628:Receptors, Thrombopoietin; C082218:MPL protein, human; C520809:eltrombopag