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

TI Ionova1,2, OYu Vinogradova3,4,5, TV Shelekhova6, DG Sherstnev6, AV Proidakov7, EV Lyyurova7, MM Pankrashkina3, LA Mukha3, EE Markova3, NV Novitskaya3, TI Pospelova8, TN Babaeva8, NB Bulieva9, GB Kuchma10, EA Andreevskaya11, EE Zinina12, MV Frolova13, KB Trizna14, IL Shestopalova15, TV Shneider16, SA Volkova17, SG Zakharov18, II Mulina19, IE Solov’eva19, AA Myasnikov20, AA Kuchin20, LB Khvorostenko21, NM Porfirieva1, TP Nikitina1,2, VV Ptushkin3,4,5, SV Gritsaev22

1 Multinational Center for Quality of Life Research, 1 Artilleriiskaya ul., Saint Petersburg, Russian Federation, 191014

2 NI Pirogov Clinic for High Medical Technology, Saint Petersburg State University, 154 Fontanki nab., Saint Petersburg, Russian Federation, 198103

3 Moscow Municipal Center of Hematology, SP Botkin Municipal Clinical Hospital, 5 2-i Botkinskii pr-d, Moscow, Russian Federation, 125284

4 NI Pirogov Russian National Research Medical University, 1 Ostrovityanova ul., Moscow, Russian Federation, 117997

5 Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology, 1 Samory Mashela ul., Moscow, Russian Federation, 117997

6 VI Razumovskii Saratov State Medical University, 112 Bol’shaya Kazach’ya ul., Saratov, Russian Federation, 410012

7 Komi Republican Oncology Dispensary, 46 Nyuvchimskoe sh., Syktyvkar, Republic of Komi, Russian Federation, 167904

8 Novosibirsk State Medical University, 52 Krasnyi pr-t, Novosibirsk, Russian Federation, 630091

9 I Kant Baltic Federal University, 14 Aleksandra Nevskogo ul., Kaliningrad, Russian Federation, 236041

10 Orenburg State Medical University, 6 Sovetskaya ul., Orenburg, Russian Federation, 460000

11 Krai Clinical Hospital No. 1, 7 Kokhanskogo ul., Chita, Russian Federation, 672038

12 Clinical and Diagnostic Center (Hematology), Surgut District Clinical Hospital, 14 Energetikov ul., Surgut, Russian Federation, 628408

13 Vologda Regional Clinical Hospital, 17 Lechebnaya ul., Vologda, Russian Federation, 160002

14 Tomsk Regional Clinical Hospital, 96 I. Chernykh ul., Tomsk, Russian Federation, 634063

15 SI Sergeev Krai Clinical Hospital No. 1, 9 Krasnodarskaya ul., Khabarovsk, Russian Federation, 680009

16 Leningrad Regional Clinical Hospital, 45 korp. 1 lit. A Lunacharskogo pr-t, Saint Petersburg, Russian Federation, 194291

17 Privolzhsky Research Medical University, 10/1 Minina i Pozharskogo pl., Nizhny Novgorod, Russian Federation, 603005

18 MF Vladimirskii Moscow Regional Research Clinical Institute, 61/2 Shchepkina ul., Moscow, Russian Federation, 129110

19 Republican Hospital No. 1, National Medical Center, 4 Sergelyakhskoe sh., Yakutsk, Republic of Sakha (Yakutiya), Russian Federation, 677008

20 VA Baranov Republican Clinical Hospital, 3 Pirogova ul., Petrozavodsk, Republic of Karelia, Russian Federation, 185002

21 Regional Clinical Hospital No. 1, 55 Kotovskogo ul., Tyumen, Russian Federation, 625023

22 Russian Research Institute of Hematology and Transfusiology, 16 2-ya Sovetskaya ul., Saint Petersburg, Russian Federation, 191024

For correspondence: Tatyana Pavlovna Nikitina, MD, PhD, 1 Artilleriiskaya ul., Saint Petersburg, Russian Federation, 191014; Tel.: +7(962)710-17-12; e-mail: tnikitina_74@mail.ru

For citation: Ionova TI, Vinogradova OYu, Shelekhova TV, et al. 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. 2023;16(2):154–65. (In Russ).

DOI: 10.21320/2500-2139-2023-16-2-154-165


ABSTRACT

Aim. To study the quality of life in patients with chronic immune thrombocytopenia (ITP) in the process of romiplostim therapy and to assess the efficacy and safety of this drug in real-world setting.

Materials & Methods. The study enrolled adult patients with the confirmed chronic ITP diagnosis and indications for romiplostim therapy. Clinical parameters, RAND SF-36 and FACT-Th6 quality of life as well as FACIT-Fatigue scores were evaluated prior to romiplostim administration vs. 3, 6, and 12 months after the treatment onset. Patient satisfaction checklist was also administered at all study points after the start of therapy. The clinical efficacy of romiplostim was analyzed along with assessing response and time to response. To study the quality of life and fatigue changes, the Generalized Estimating Equation (GEE) method was used during the observation period. Significant fatigue changes were determined and compared in terms of the perception differences from patient’s and physician’s perspective.

Results. The study enrolled 60 chronic ITP patients treated with romiplostim in the real-world setting (mean age 51.9 years, 70 % women). The median thrombocyte count prior to romiplostim therapy was 18.5 × 109/L (interquartile range 10.8–22.3 × 109/л). On the enrollment date, 90 % of patients showed hemorrhagic syndrome. Overall response to romiplostim therapy was 98.3 % (complete response was achieved in 93.3 % of patients). After 6 months of therapy, 89.5 % of patients preserved response. After 3 months of therapy, hemorrhagic syndrome was eliminated in 81 % of patients, after 6 months the same was achieved in 93 % of patients. The median time to response was 4.4 weeks (95% confidence interval 3.6–5.3 weeks). Adverse events of grades 1/2 associated with romiplostim were reported in 6.7 % of patients. On romiplostim therapy, pronounced positive changes in quality of life were shown by all scales of the general questionnaire SF-36 and the targeted questionnaire FACT-Th6 (< 0.001). The clearest improvements were observed in role-physical and role-emotional functioning. Already after 3 months of therapy, a considerable fatigue reduction was observed and sustained for the next 6 and 12 months of romiplostim administration (< 0.001). During the therapy, the proportion of patients with fatigue impacting various aspects of functioning became considerably smaller. The vast majority of patients (85 %) were satisfied with the treatment. Discrepancies between patients’ and physicians’ evaluations of fatigue were also identified during the treatment.

Conclusion. The results of the present multi-center observational study demonstrate high efficacy and safety of romiplostim for chronic ITP patients in the real-world setting. Romiplostim therapy yields considerable quality of life improvement and fatigue reduction. To optimize the patient monitoring system and patient-centered ITP treatment in the real-world setting, it is advisable to use the standardized questionnaires assessing quality of life and fatigue.

Keywords: chronic immune thrombocytopenia, quality of life, romiplostim, efficacy, safety, data in the real-world setting.

Received: October 21, 2022

Accepted: March 1, 2023

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REFERENCES

  1. Меликян А.Л., Пустовал Е.И., Цветаева Н.В. и др. Национальные клинические рекомендации по диагностике и лечению идиопатической тромбоцитопенической пурпуры (первичной иммунной тромбоцитопении) у взрослых (редакция 2018 г.) [электронный документ]. Доступно по: https://npngo.ru/uploads/media_document/283/5eb37419-9276-4e9a-b075-0e26a788f623.pdf. Ссылка активна на 20.10.2022.
    [Melikyan AL, Pustoval EI, Tsvetaeva NV, et al. National clinical guidelines on diagnosis and treatment of idiopathic thrombocytopenic purpura (primary immune thrombocytopenia) in adults (edition 2018). (Internet) Available from: https://npngo.ru/uploads/media_document/283/5eb37419-9276-4e9a-b075-0e26a788f623.pdf. Accessed 10.2022. (In Russ)]
  2. 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. 2009;113(11):2386–93. doi: 10.1182/blood-2008-07-162503.
  3. Vianelli N, Auteri G, Buccisano F, et al. Refractory primary immune thrombocytopenia (ITP): current clinical challenges and therapeutic perspectives. Ann Hematol. 2022;101:963–78. doi: 10.1007/s00277-022-04786-y.
  4. Trotter P, Hill QA. Immune thrombocytopenia: improving quality of life and patient outcomes. Patient Relat Outcome Meas. 2018;9:369–84. doi: 10.2147/PROM.S140932.
  5. Efficace F, Mandelli F, Fazi P, et al. Health-related quality of life and burden of fatigue in patients with primary immune thrombocytopenia by phase of disease. Am J Hematol. 2016;91(10):995–1001. doi: 10.1002/ajh.24463.
  6. Tarniceriu CC, Rudeanu SA, Delianu C, et al. Quality of Life Today in Patients with Chronic Immune Thrombocytopenic Purpura. Res Pract Thromb Haemost. 2020;4(Suppl 1): Abstract PB1479.
  7. Cooper N, Kruse A, Kruse C, et al. Immune thrombocytopenia (ITP) World Impact Survey(I-WISh): Impact of ITP on health-related quality of life. Am J Hematol. 2021;96(2):199–207. doi: 10.1002/ajh.26036.
  8. Kruse C, Kruse A, DiRaimo J. Immune thrombocytopenia: the patient’s perspective. Ann Blood. 2021;6:9. doi: 10.21037/aob-20-57.
  9. Newton JL, Reese JA, Watson SI, et al. Fatigue in adult patients with primary immune thrombocytopenia. Eur J Haematol. 2011;86(5):420–9. doi: 10.1111/j.1600-0609.2011.01587.x.
  10. Hill OA, Newland AC. Fatigue in immune thrombocytop Br J Haematol. 2015;170(2):141–9. doi: 10.1111/bjh.13385.
  11. Yang R, Yao H, Lin L, et al. Health-Related Quality of Life and Burden of Fatigue in Chinese Patients with Immune Thrombocytopenia: A Cross-Sectional Study. Indian J Hematol Blood Transfus. 2020;36(1):104–11. doi: 10.1007/s12288-019-01124-7.
  12. Neunert CE, Cooper N. Evidence-based management of immune thrombocytopenia: ASH guideline update. Hematology Am Soc Hematol Educ Program. 2018;2018(1):568–75. doi: 10.1182/asheducation-2018.1.568.
  13. Neunert C, Terrell DR, Arnold DM, et al. American Society of Hematology 2019 guidelines for immune thrombocytopenia. Blood Adv. 2019;3(23):3829–66. doi: 10.1182/bloodadvances.2019000966.
  14. Matzdorff A, Meyer O, Ostermann H, et al. Immune Thrombocytopenia – Current Diagnostics and Therapy: Recommendations of a Joint Working Group of DGHO, OGHO, SGH, GPOH, and DGTI. Oncol Res Treat. 2018;41(Suppl 5):1–30. doi: 10.1159/000492187.
  15. European Medicines Agency. Reflection paper on the regulatory guidance for the use of health-related quality of life (HRQL) measures in the evaluation of medicinal products. (Internet) Available from: http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500003637.pdf. (accessed 20.10.2022).
  16. S. Department of Health and Human Services FDA Center for Drug Evaluation and Research; U.S. Department of Health and Human Services FDA Center for Biologics Evaluation and Research; U.S. Department of Health and Human Services FDA Center for Devices and Radiological Health. Guidance for industry: patient-reported outcome measures: use in medical product development to support labeling claims: draft guidance. Health Qual Life Outcomes. 2006;4:79. doi: 10.1186/1477-7525-4-79.
  17. 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. 2008;371(9610):395–403. doi: 10.1016/S0140-6736(08)60203-2.
  18. Bussel JB, Kuter DJ, Pullarkat V, et al. Safety and efficacy of long-term treatment with romiplostim in thrombocytopenic patients with chronic ITP. Blood. 2009;113(10):2161–71. doi: 10.1182/blood-2008-04-150078.
  19. Kuter DJ, Rummel M, Boccia R, et al. Romiplostim or standard of care in patients with immune thrombocytopenia. N Engl J Med. 2010;363(20):1889–99. doi: 10.1056/NEJMoa1002625.
  20. Cooper N, Terrinoni I, Newland A. The efficacy and safety of romiplostim in adult patients with chronic immune thrombocytopenia. Ther Adv Hematol. 2012;3(5):291–8. doi: 10.1177/2040620712453596.
  21. George JN, Mathias SD, Go RS, et al. Improved quality of life for romiplostim-treated patients with chronic immune thrombocytopenic purpura: results from two randomized, placebo-controlled trials. Br J Haematol. 2008;144(3):409–15. doi: 10.1111/j.1365-2141.2008.07464.x.
  22. Kuter DJ, Mathias SD, Rummel M, et al. Health-related quality of life in nonsplenectomized immune thrombocytopenia patients receiving romiplostim or medical standard of care. Am J Hematol. 2012;87(5):558–61. doi: 10.1002/ajh.23163.
  23. Sanz MA, Aledort L, Mathias SD, et al. Analysis of EQ-5D scores from two phase 3 clinical trials of romiplostim in the treatment of immune thrombocytopenia (ITP). Value Health. 2011;14(1):90–6. doi: 10.1016/j.jval.2010.10.017.
  24. Rovo A, Cantoni N, Samii K, et al. Real-world impact of primary immune thrombocytopenia and treatment with thrombopoietin receptor agonists on quality of life based on patient-reported experience: Results from a questionnaire conducted in Switzerland, Austria, and Belgium. PLoS ONE. 2022;17(4):e0267342. doi: 10.1371/journal.pone.0267342.
  25. Caocci G, Efficace F, Mulas O, et al. Health-related quality of life profile of patients with immune thrombocytopenia in the real life is impaired by splenectomy. Ann Hematol. 2022;101(4):749–54. doi: 10.1007/s00277-021-04750-2.
  26. Hays RD, Sherbourne CD, Mazel RM. User’s Manual for Medical Outcomes Study (MOS) Core measures of health-related quality of life, Santa Monica, Calif.: RAND Corporation, MR-162-RC, 1995. (Internet) Available from: https://www.rand.org/pubs/monograph_reports/MR162.html (accessed 20.10.2022).
  27. Snyder CF, Mathias SD, Cella D, et al. Health-related quality of life of immune thrombocytopenic purpura patients: results from a web-based survey. Curr Med Res Opin. 2008;24(10):2767–76. doi: 10.1185/03007990802377461.
  28. Cella D, Beaumont JL, Webster KA, et al. Measuring the concerns of cancer patients with low platelet counts: the Functional Assessment of Cancer TherapyThrombocytopenia (FACT-Th) questionnaire. Support Care Cancer. 2006;14(12):1220–31. doi: 10.1007/s00520-006-0102-1.
  29. Yellen SB, Cella DF, Webster K, et al. Measuring fatigue and other anemia-related symptoms with the Functional Assessment of Cancer Therapy (FACT) measurement system. J Pain Symptom Manage. 1997;13(2):63–74. doi: 10.1016/s0885-3924(96)00274-6.
  30. Cella D, Johansson P, Ueda Y, et al. Clinically Important Difference for the FACIT-Fatigue Scale in Paroxysmal Nocturnal Hemoglobinuria: A Derivation from International PNH Registry Patient Data. Blood. 2021;138(1):1952. doi: 10.1182/blood-2021-153127.
  31. Atkinson MJ, Sinha A, Hass SL, et al. Validation of a general measure of treatment satisfaction, the Treatment Satisfaction Questionnaire for Medication (TSQM), using a national panel study of chronic disease. Health Qual Life Outcomes. 2004;2:12. doi: 10.1186/1477-7525-2-12.
  32. Common Terminology Criteria for Adverse Evens (CTCAE 4) Version 4.0. (Internet) Available from: https://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03/CTCAE_4.03_2010-06-14_QuickReference_8.5х11.pdf (accessed 20.10.2022).
  33. Mouelhi Y, Jouve E, Castelli C, et al. How is the minimal clinically important difference established in health-related quality of life instruments? Review of anchors and methods. Health Qual Life Outcomes. 2020;18(1):136. doi: 10.1186/s12955-020-01344-w.
  34. Зотова И.И., Грицаев С.В., Шилова Е.Р. и др. Агонисты рецептора тромбопоэтина в лечении идиопатической тромбоцитопенической пурпуры (первичной иммунной тромбоцитопении): эффективность и безопасность в повседневной клинической практике. Клиническая онкогематология. 2017;10(1):93–100. doi: 10.21320/2500-2139-2017-10-1-93-100.
    [Zotova II, Gritsaev SV, Shilova ER, et al. Thrombopoietin Receptor Agonists in Treatment of Idiopathic Thrompocytopenic Purpura (Primary Immune Thrombocytopenia): Efficacy and Safety in Everyday Clinical Practice. Clinical oncohematology. 2017;10(1):93–100. doi: 10.21320/2500-2139-2017-10-1-93-100. (In Russ)]
  35. Птушкин В.В., Виноградова О.Ю., Панкрашкина М.М. и др. Агонисты рецептора тромбопоэтина в лечении хронической резистентной первичной иммунной тромбоцитопении: эффективность и безопасность в повседневной клинической практике. Терапевтический архив. 2018;90(7):70–6. doi: 10.26442/terarkh201890770-76.
    [Ptushkin VV, Vinogradova OYu, Pankrashkina MM, et al. Thrombopoietin Receptor Agonists in the Treatment of Chronic Resistant Primary Immune Thrombocytopenia: Efficacy and Safety Data in Real Clinical Practice. Terapevticheskii arkhiv. 2018;90(7):70–6. doi: 10.26442/terarkh201890770-76. (In Russ)]
  36. Контиевский И.Н., Голенков А.К. Эффективность агонистов тромбопоэтиновых рецепторов: ромиплостим, элтромбопаг у больных с рецидивирующей первичной иммунной тромбоцитопенией. Вестник гематологии. 2019;15(4):8–13.
    [Kontievskii IN, Golenkov AK. Efficacy of thrombopoetin receptor agonists romiplostim, eltrombopag in patients with relapsed primary immune thrombocytopenia. Vestnik gematologii. 2019;15(4):8–13. (In Russ)]
  37. 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. 2013;161(3):411–23. doi: 10.1111/bjh.12260.
  38. Forsythe A, Schneider J, Pham T, et al. Real-world evidence on clinical outcomes in immune thrombocytopenia treated with thrombopoietin receptor agonists. J Comp Eff Res. 2020;9(7):447–57. doi: 10.2217/cer-2019-0177.