Real-world evidence on clinical outcomes in immune thrombocytopenia treated with thrombopoietin receptor agonists
Publication: Journal of Comparative Effectiveness Research
Abstract
Aim: Eltrombopag and romiplostim are US FDA approved for treatment of immune thrombocytopenia in patients with insufficient response to other treatments. Clinical or real-world data comparing outcomes of the two drugs are limited. Methods: This retrospective cross-sectional study sought information on bleeding-related episodes (BREs), adverse events (AEs) and other outcomes of eltrombopag or romiplostim treatment in immune thrombocytopenia. Results: Patients receiving eltrombopag experienced significantly reduced BREs, severe BREs, rescue medication use and platelet transfusions. Diarrhea and headache were significantly less frequent in patients receiving eltrombopag; other AEs occurred equally in both groups. Conclusion: There may be a potential advantage for the use of eltrombopag versus romiplostim in the practice settings studied, based on rates of BREs and AEs and rescue medication utilization.
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References
1.
Rodeghiero F, Stasi R, Gernsheimer T et al. Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children: report from an international working group. Blood 113(11), 2386–2393 (2009).
2.
Altomare I, Cetin K, Wetten S, Wasser JS. Rate of bleeding-related episodes in adult patients with primary immune thrombocytopenia: a retrospective cohort study using a large administrative medical claims database in the US. Clin. Epidemiol. 8, 231–239 (2016).
3.
Terrell DR, Beebe LA, Vesely SK, Neas BR, Segal JB, George JN. The incidence of immune thrombocytopenic purpura in children and adults: a critical review of published reports. Am. J. Hematol. 85(3), 174–180 (2010).
4.
Mathias SD, Gao SK, Miller KL et al. Impact of chronic immune thrombocytopenic purpura (ITP) on health-related quality of life: a conceptual model starting with the patient perspective. Health Qual. Life Outcomes 6, 13 (2008).
5.
McMillan R, Bussel JB, George JN, Lalla D, Nichol JL. Self-reported health-related quality of life in adults with chronic immune thrombocytopenic purpura. Am. J. Hematol. 83(2), 150–154 (2008).
6.
McMillan R. Therapy for adults with refractory chronic immune thrombocytopenic purpura. Ann. Intern. Med. 126(4), 307–314 (1997).
7.
Lin J, Zhang X, Li X et al. Cost of bleeding-related episodes in adult patients with primary immune thrombocytopenia: a population-based retrospective cohort study of administrative claims data for commercial payers in the United States. Clin. Ther. 39(3), 603.e1–609.e1 (2017).
8.
Saleh MN, Fisher M, Grotzinger KM. Analysis of the impact and burden of illness of adult chronic ITP in the US. Curr. Med. Res. Opin. 25(12), 2961–2969 (2009).
9.
Arnold DM. Bleeding complications in immune thrombocytopenia. Hematology Am. Soc. Hematol. Educ. Program 2015, 237–242 (2015).
10.
Schoonen WM, Kucera G, Coalson J et al. Epidemiology of immune thrombocytopenic purpura in the General Practice Research Database. Br. J. Haematol. 145(2), 235–244 (2009).
11.
Frederiksen H, Maegbaek ML, Norgaard M. Twenty-year mortality of adult patients with primary immune thrombocytopenia: a Danish population-based cohort study. Br. J. Haematol. 166(2), 260v267 (2014).
12.
Portielje JE, Westendorp RG, Kluin-Nelemans HC, Brand A. Morbidity and mortality in adults with idiopathic thrombocytopenic purpura. Blood 97(9), 2549–2554 (2001).
13.
Cohen YC, Djulbegovic B, Shamai-Lubovitz O, Mozes B. The bleeding risk and natural history of idiopathic thrombocytopenic purpura in patients with persistent low platelet counts. Arch. Intern. Med. 160(11), 1630–1638 (2000).
14.
Lambert MP, Gernsheimer TB. Clinical updates in adult immune thrombocytopenia. Blood 129(21), 2829–2835 (2017).
15.
Neunert C, Terrell DR, Arnold DM et al. American Society of Hematology 2019 guidelines for immune thrombocytopenia. Blood Adv. 3(23), 3829–3866 (2019).
16.
Bohn JP, Steurer M. Current and evolving treatment strategies in adult immune thrombocytopenia. Memo 11(3), 241–246 (2018).
17.
Harris E, Tiganescu A, Tubeuf S, Mackie SL. The prediction and monitoring of toxicity associated with long-term systemic glucocorticoid therapy. Curr. Rheumatol. Rep. 17(6), 513 (2015).
18.
Cuker A. Transitioning patients with immune thrombocytopenia to second-line therapy: challenges and best practices. Am. J. Hematol. 93(6), 816–823 (2018).
19.
Cheng G, Saleh MN, Marcher C et al. Eltrombopag for management of chronic immune thrombocytopenia (RAISE): a 6-month, randomised, Phase III study. Lancet 377(9763), 393–402 (2011).
20.
Chaturvedi S, Arnold DM, McCrae KR. Splenectomy for immune thrombocytopenia: down but not out. Blood 131(11), 1172–1182 (2018).
21.
Stasi R, Cooper N, Del Poeta G et al. Analysis of regulatory T-cell changes in patients with idiopathic thrombocytopenic purpura receiving B cell-depleting therapy with rituximab. Blood 112(4), 1147–1150 (2008).
22.
Rituxan (Rituximab). Prescribing information. Genentech, Inc, CA, USA (2016).
23.
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(9610), 395–403 (2008).
24.
Said Q, Lal LS, Nezami B. Evaluation of treatment outcomes after second-line treatment among patients with immune thrombocytopenia. Blood 132, P3765 (2018).
25.
Michel M. Immune thrombocytopenic purpura: epidemiology and implications for patients. Eur. J. Haematol. Suppl. 71, 3–7 (2009).
26.
Zhou Z, Yang L, Chen Z et al. Health-related quality of life measured by the Short Form 36 in immune thrombocytopenic purpura: a cross-sectional survey in China. Eur. J. Haematol. 78(6), 518–523 (2007).
27.
Provan D, Stasi R, Newland AC et al. International consensus report on the investigation and management of primary immune thrombocytopenia. Blood 115(2), 168–186 (2010).
28.
Wang L, Gao Z, Chen XP et al. Efficacy and safety of thrombopoietin receptor agonists in patients with primary immune thrombocytopenia: a systematic review and meta-analysis. Sci. Rep. 6, 39003 (2016).
29.
Stapff M. Use of electronic health data in clinical development. ECV Editio Cantor Verlag 79(2), 204–210 (2017).
30.
NPlate. Package insert. Amgen Inc, CA, USA.
31.
Promacta. Package Insert. Novartis Pharmaceuticals, NJ, USA.
32.
Tremblay G, Bhor M, Roy A et al. Cost-consequence model comparing eltrombopag and romiplostim for pediatric patients with previously-treated chronic immune thrombocytopenia. Blood 130(Suppl. 1), 2146–2146 (2017).
33.
Forsythe A, Bhor M, Roy A, Socorro O Portella M, Kwon C, Tremblay G. Economic burden of immune thrombocytopenia (ITP) in patients receiving eltrombopag (EPAG) and romiplostim (ROMI): real world evidence from 26 US institutions. Value Health 20(9), A552 (2017).
34.
Kwon C, Forsythe A, Roy A, Bhor M, Socorro O Portella M, Tremblay G. Health care resource use (HCRU) due to bleeding related episodes (BRE) in patients with immune thrombocytopenic purpura (ITP) receiving eltrombopag (EPAG), romiplostim (ROMI), or rituximab (RITUX): real world evidence (RWE) from 27 US institutions. Value Health 20(9), A558 (2017).
35.
Ghanima W, Cooper N, Rodeghiero F, Godeau B, Bussel JB. Thrombopoietin receptor agonists: ten years later. Haematologica 104(6), 1112–1123 (2019).
36.
Gonzalez-Porras JR, Bastida JM. Eltrombopag in immune thrombocytopenia: efficacy review and update on drug safety. Ther. Adv. Drug Saf. 9(6), 263–285 (2018).
37.
Bussel JB, Kuter DJ, George JN et al. AMG 531, a thrombopoiesis-stimulating protein, for chronic ITP. N. Engl. J. Med. 355(16), 1672–1681 (2006).
38.
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(1), 71–80 (2011).
39.
Bussel JB, Provan D, Shamsi T et al. Effect of eltrombopag on platelet counts and bleeding during treatment of chronic idiopathic thrombocytopenic purpura: a randomised, double-blind, placebo-controlled trial. Lancet 373, 641–648 (2009).
40.
Bussel JB, Cheng G, Saleh MN et al. Eltrombopag for the treatment of chronic idiopathic thrombocytopenic purpura. N. Engl. J. Med. 357, 2237–2247 (2007).
41.
Tomiyama Y, Miyakawa Y, Okamoto S et al. A lower starting dose of eltrombopag is efficacious in Japanese patients with previously treated chronic immune thrombocytopenia. J. Thromb. Haemost. 10, 799–806 (2012).
42.
Kuter DJ, Rummel M, Boccia R et al. Romiplostim or standard of care in patients with immune thrombocytopenia. N. Engl. J. Med. 363(20), 1889–1899 (2010).
43.
Bussel JB, Kuter DJ, Pullarkat V, Lyons RM, Guo M, Nichol JL. Safety and efficacy of long-term treatment with romiplostim in thrombocytopenic patients with chronic ITP. Blood 113(10), 2161–2171 (2009).
44.
Wong RSM, Saleh MN, Khelif A et al. Safety and efficacy of long-term treatment of chronic/persistent ITP with eltrombopag: final results of the EXTEND study. Blood 130(23), 2527–2536 (2017).
45.
Kuter DJ, Bussel JB, Newland A et al. Long-term treatment with romiplostim in patients with chronic immune thrombocytopenia: safety and efficacy. Br. J. Haematol. 161(3), 411–423 (2013).
46.
Kuter DJ, Macahilig C, Grotzinger KM et al. Treatment patterns and clinical outcomes in patients with chronic immune thrombocytopenia (ITP) switched to eltrombopag or romiplostim. Int. J. Hematol. 101(3), 255–263 (2015).
47.
Khellaf M, Viallard JF, Hamidou M et al. A retrospective pilot evaluation of switching thrombopoietic receptor-agonists in immune thrombocytopenia. Haematologica 98(6), 881–887 (2013).
48.
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(1), 58–64 (2018).
49.
González-Porras JR, Godeau B, Carpenedo M. Switching thrombopoietin receptor agonist treatments in patients with primary immune thrombocytopenia. Ther. Adv. Hematol. 10, 20406207198379062019 (2019).
50.
Moulis G, Bagheri H, Sailler L et al. Are adverse drug reaction patterns different between romiplostim and eltrombopag? 2009–2013 French PharmacoVigilance assessment. Eur. J. Intern. Med. 25(8), 777–780 (2014).
51.
Al-Samkari H, Kuter DJ. Thrombopoietin level predicts response to treatment with eltrombopag and romiplostim in immune thrombocytopenia. Am. J. Hematol. 93(12), 1501–1508 (2018).
52.
Arnold DM. Platelet count or bleeding as the outcome in ITP trials? Am. J. Hematol. 87(10), 945–946 (2012).
53.
Trotter P, Hill QA. Immune thrombocytopenia: improving quality of life and patient outcomes. Patient Relat. Outcome Meas. 9, 369–384 (2018).
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Pages: 447 - 457
PubMed: 32175766
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© 2020 Future Medicine Ltd.
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Received: 22 November 2019
Accepted: 11 February 2020
Published online: 16 March 2020
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Real-world evidence on clinical outcomes in immune thrombocytopenia treated with thrombopoietin receptor agonists. (2020) Journal of Comparative Effectiveness Research. DOI: 10.2217/cer-2019-0177
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- O. Yu. Vinogradova, M. M. Pankrashkina, Anna Leonidovna Neverova, M. V. Chernikov, L. A. Mukha, D. I. Shikhbabaeva, V. V. Ptushkin, Primary Immune Thrombocytopenia and Thrombopoietin Receptor Agonists: Feasibilities of Treatment Discontinuation upon Achieving Stable Complete Platelet Response, Clinical Oncohematology, 10.21320/2500-2139-2023-16-4-413-425, 16, 4, (413-425), (2024).
- T. I. Ionova, O. Yu. Vinogradova, T. V. Shelekhova, D. G. Sherstnev, A. V. Proidakov, E. V. Lyyurova, M. M. Pankrashkina, L. A. Mukha, E. E. Markova, N. V. Novitskaya, T. I. Pospelova, T. N. Babaeva, N. B. Bulieva, G. B. Kuchma, E. A. Andreevskaya, E. E. Zinina, M. V. Frolova, K. B. Trizna, I. L. Shestopalova, T. V. Shneider, S. A. Volkova, S. G. Zakharov, I. I. Mulina, I. E. Solov’eva, A. A. Myasnikov, A. A. Kuchin, L. B. Khvorostenko, N. M. Porfirieva, Tatyana Pavlovna Nikitina, V. V. Ptushkin, S. V. Gritsaev, Quality of Life Changes in Patients with Chronic Immune Thrombocytopenia in the Process of Romiplostim Therapy, its Efficacy and Safety in the Real-World Setting: Results of a Multi-Center Observational Study, Clinical Oncohematology, 10.21320/2500-2139-2023-16-2-154-165, 16, 2, (154-165), (2024).
- Raymond Siu Ming Wong, İrfan Yavaşoğlu, Mohamed A. Yassin, Pınar Tarkun, Sung-Soo Yoon, Xie Wei, Ashraf Elghandour, Pantep Angchaisuksiri, Mehmet Ozcan, Renchi Yang, Mervat Mattar, Masiur Rahman, Sara Ingles, Michael Goldbrunner, Jennifer A. Frueh, Jun Ho Jang, Eltrombopag in patients with chronic immune thrombocytopenia in Asia-Pacific, the Middle East, and Turkey: final analysis of CITE, Blood Advances, 10.1182/bloodadvances.2022008287, 7, 17, (4773-4781), (2023).
- Ji Yun Lee, Ju-Hyun Lee, Sang-A Kim, Koung Jin Suh, Ji-Won Kim, Se Hyun Kim, Jeong-Ok Lee, Jin Won Kim, Yu Jung Kim, Keun-Wook Lee, Jee Hyun Kim, Jong Seok Lee, Soo-Mee Bang, Treatment patterns of thrombopoietin receptor agonists among adults with primary immune thrombocytopenia: A Korean nationwide population-based study, Thrombosis Research, 10.1016/j.thromres.2022.03.015, 213, (114-118), (2022).
- Michael Fillitz, Barbara Dixer, Felix Keil, Practical considerations for the management of immune thrombocytopenic purpura, memo - Magazine of European Medical Oncology, 10.1007/s12254-021-00771-9, 14, 4, (350-354), (2021).
- Hafiz Abdul Waqas Ahmed, Ahmed Taher Masoud, Jia Han, Ahmed Adel Sofy, Ahmed Saeed Ahmed, Ahmed Taha Abdesattart, Emmanuel Kwateng Drokow, Kai Sun, Eltrombopag Effectiveness and Tolerability in Chronic Immune Thrombocytopenia: A Meta-Analysis, Clinical and Applied Thrombosis/Hemostasis, 10.1177/10760296211005555, 27, (2021).