臨床検査68巻2号

2024年02月発行

今月の特集1 血栓止血領域における抗体医薬

特発性血小板減少性紫斑病（一次性免疫性血小板減少症）

著者： 柏木浩和¹

所属機関： ¹大阪大学医学部附属病院輸血部

ページ範囲：P.126 - P.132

Point

●副腎皮質ステロイド不応性あるいは依存性特発性血小板減少性紫斑病（ITP）のセカンドライン治療として，ロミプロスチムおよびリツキシマブは，エルトロンボパグおよび脾臓摘出術とともに推奨されている．

●トロンボポエチン受容体作動薬であるロミプロスチムは高い有効率を示すが，毎週の受診が必要な皮下注製剤である．

●リツキシマブは短期間で治療を終了させられる点が長所であるが，長期的な有効率が低い．

●セカンドラインとして新たな治療薬が使用可能となってきており，どのように治療薬を選択するかが今後の課題である．

参考文献

1）柏木浩和：免疫性血小板減少症の病態と治療．臨血　64：397-405，2023

2）厚生労働省難治性疾患政策研究事業　血液凝固異常症等に関する研究班　「ITP治療の参照ガイド」作成委員会：成人特発性血小板減少性紫斑病治療の参照ガイド　2019改訂版．臨血　60：877-896，2019

3）Nomura S, Dan K, Hotta T, et al：Effects of pegylated recombinant human megakaryocyte growth and development factor in patients with idiopathic thrombocytopenic purpura. Blood　100：728-730，2002

4）Li J, Yang C, Xia Y, et al：Thrombocytopenia caused by the development of antibodies to thrombopoietin. Blood　98：3241-3248，2001

5）Kuter DJ：New thrombopoietic growth factors. Blood　109：4607-4616，2007

6）加藤尚志：血小板産生因子トロンボポエチンの発見と次世代受容体作動薬の開発　創薬につなげる発見研究展開にヒント．化と生　56：331-337，2018

7）González-Porras JR, Godeau B, Carpenedo M：Switching thrombopoietin receptor agonist treatments in patients with primary immune thrombocytopenia. Ther Adv Hematol　10：2040620719837906，2019

8）Bussel JB, Kuter DJ, George JN, et al：AMG 531, a thrombopoiesis-stimulating protein, for chronic ITP. N Engl J Med　355：1672-1681，2006

9）Kuter DJ, Bussel JB, Lyons RM, et al：Efficacy of romiplostim in patients with chronic immune thrombocytopenic purpura: a double-blind randomised controlled trial. Lancet　371：395-403，2008

10）Kuter DJ, Rummel M, Boccia R, et al：Romiplostim or standard of care in patients with immune thrombocytopenia. N Engl J Med　363：1889-1899，2010

11）Shirasugi Y, Ando K, Miyazaki K, et al：Romiplostim for the treatment of chronic immune thrombocytopenia in adult Japanese patients: a double-blind, randomized Phase III clinical trial. Int J Hematol　94：71-80，2011

12）Cines DB, Wasser J, Rodeghiero F, et al：Safety and efficacy of romiplostim in splenectomized and nonsplenectomized patients with primary immune thrombocytopenia. Haematologica　102：1342-1351，2017

13）Cantoni S, Carpenedo M, Mazzucconi MG, et al：Alternate use of thrombopoietin receptor agonists in adult primary immune thrombocytopenia patients: A retrospective collaborative survey from Italian hematology centers. Am J Hematol　93：58-64，2018

14）Rodeghiero F：Is ITP a thrombophilic disorder?. Am J Hematol　91：39-45，2016

15）Ghanima W, Geyer JT, Lee CS, et al：Bone marrow fibrosis in 66 patients with immune thrombocytopenia treated with thrombopoietin-receptor agonists: a single-center, long-term follow-up. Haematologica　99：937-944，2014

16）Brynes RK, Orazi A, Theodore D, et al：Evaluation of bone marrow reticulin in patients with chronic immune thrombocytopenia treated with eltrombopag: Data from the EXTEND study. Am J Hematol　90：598-601，2015

17）Janssens A, Rodeghiero F, Anderson D, et al：Changes in bone marrow morphology in adults receiving romiplostim for the treatment of thrombocytopenia associated with primary immune thrombocytopenia. Ann Hematol　95：1077-1087，2016

18）Brynes RK, Wong RS, Thein MM, et al：A 2-Year, Longitudinal, Prospective Study of the Effects of Eltrombopag on Bone Marrow in Patients with Chronic Immune Thrombocytopenia. Acta Haematol　137：66-72，2017

19）Carpenedo M, Cantoni S, Coccini V, et al：Response loss and development of neutralizing antibodies during long-term treatment with romiplostim in patients with immune thrombocytopenia: a case series. Eur J Haematol　97：101-103，2016

20）Neunert C, Terrell DR, Arnold DM, et al：American Society of Hematology 2019 guidelines for immune thrombocytopenia. Blood Adv　3：3829-3866，2019

21）Provan D, Arnold DM, Bussel JB, et al：Updated international consensus report on the investigation and management of primary immune thrombocytopenia. Blood Adv　3：3780-3817，2019

22）Zaja F, Volpetti S, Chiozzotto M, et al：Long-term follow-up analysis after rituximab salvage therapy in adult patients with immune thrombocytopenia. Am J Hematol　87：886-889，2012

23）Xiao Z, Murakhovskaya I：Rituximab resistance in ITP and beyond. Front Immunol　14：1215216，2023

24）Ghanima W, Khelif A, Waage A, et al：Rituximab as second-line treatment for adult immune thrombocytopenia (the RITP trial): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet　385：1653-1661，2015

25）Tjønnfjord E, Holme PA, Darne B, et al：Long-term outcomes of patients treated with rituximab as second-line treatment for adult immune thrombocytopenia - Follow-up of the RITP study. Br J Haematol　191：460-465，2020

26）Miyakawa Y, Katsutani S, Yano T, et al：Efficacy and safety of rituximab in Japanese patients with relapsed chronic immune thrombocytopenia refractory to conventional therapy. Int J Hematol　102：654-661，2015

27）Marangon M, Vianelli N, Palandri F, et al：Rituximab in immune thrombocytopenia: gender, age, and response as predictors of long-term response. Eur J Haematol　98：371-377，2017

28）Feng R, Liu X, Zhao Y, et al：GPIIb/IIIa autoantibody predicts better rituximab response in ITP. Br J Haematol　182：305-307，2018

29）Arnold DM, Dentali F, Crowther MA, et al：Systematic review: efficacy and safety of rituximab for adults with idiopathic thrombocytopenic purpura. Ann Intern Med　146：25-33，2007

30）Khellaf M, Charles-Nelson A, Fain O, et al：Safety and efficacy of rituximab in adult immune thrombocytopenia: results from a prospective registry including 248 patients. Blood　124：3228-3236，2014

31）Deshayes S, Khellaf M, Zarour A, et al：Long-term safety and efficacy of rituximab in 248 adults with immune thrombocytopenia: Results at 5 years from the French prospective registry ITP-ritux. Am J Hematol　94：1314-1324，2019

32）Patel VL, Mahévas M, Lee SY, et al：Outcomes 5 years after response to rituximab therapy in children and adults with immune thrombocytopenia. Blood　119：5989-5995，2012

33）Crickx E, Chappert P, Sokal A, et al：Rituximab-resistant splenic memory B cells and newly engaged naive B cells fuel relapses in patients with immune thrombocytopenia. Sci Transl Med　13：eabc3961，2021

34）Mahévas M, Patin P, Huetz F, et al：B cell depletion in immune thrombocytopenia reveals splenic long-lived plasma cells. J Clin Invest　123：432-442，2013

35）Rodeghiero F：Recent progress in ITP treatment. Int J Hematol　117：316-330，2023