Skip to main content
SpringerLink
Log in

Cost-Utility Analysis of Pegaspargase for the Treatment of Acute Lymphoblastic Leukemia in Greece

  • Original Research Article
  • Published:
Clinical Drug Investigation Aims and scope Submit manuscript

A Correction to this article was published on 29 December 2022

This article has been updated

Abstract

Background and Objective

Acute lymphoblastic leukemia (ALL) is an acute, rapidly progressing and life-threatening form of cancer involving immature lymphocytes called lymphoblasts. ALL is the most common subtype of leukemia in children and adolescents. The aim of the present study was to assess the cost-utility of pegaspargase versus l-asparaginase, both followed by Erwinase in the therapy sequence, as a treatment option for pediatric, adolescent, and adult patients with ALL in Greece.

Methods

A published cost-utility model comprising a decision tree and a state-transition Markov model was adapted from a public payer perspective to compare a pegaspargase treatment sequence with an l-asparaginase sequence. Efficacy and safety data, as well as utility values, were extracted from the published literature. Direct costs pertaining to drug acquisition, administration, and management of hypersensitivity were considered in the analysis (€2020). Model-extrapolated outcomes included quality-adjusted life-years (QALYs), costs, and incremental cost-effectiveness ratios (ICER). All future outcomes were discounted at 3.5% per annum. Sensitivity analyses were used to explore the impact of changing input data.

Results

The analysis showed that the pegaspargase sequence was estimated to produce 0.05 additional QALYs (18.12 vs. 18.07) and lower cost of − €1698 compared with l-asparaginase, indicating that the pegaspargase sequence was a dominant treatment strategy (improved outcomes with reduced costs) compared with l-asparaginase. Deterministic sensitivity analysis confirmed the cost-effective profile of pegaspargase. At the defined willingness-to-pay threshold of €54,000/QALY gained, probabilistic sensitivity analysis showed that pegaspargase had a 100% probability of being cost effective relative to the l-asparaginase sequence.

Conclusion

The pegaspargase sequence was found to be less costly and more effective (in terms of QALYs) in relation to the l-asparaginase sequence, representing a dominant strategic option for Greek public payers in ALL.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Change history

References

  1. Medawar CV, Mosegui GBG, Vianna CMM, et al. PEG-asparaginase and native Escherichia coli l-asparaginase in acute lymphoblastic leukemia in children and adolescents: a systematic review. Hematol Transfus Cell Ther. 2020;42(1):54–61. https://doi.org/10.1016/j.htct.2019.01.013.

    Article  Google Scholar 

  2. Hoelzer D, Bassan R, Dombret H, et al. Acute lymphoblastic leukaemia in adult patients: ESMO Clinical Practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2016;27(Suppl 5):v69–82. https://doi.org/10.1093/annonc/mdw025.

    Article  CAS  Google Scholar 

  3. Asselin BL. The three asparaginases. Comparative pharmacology and optimal use in childhood leukemia. Adv Exp Med Biol. 1999;457:621–9.

    Article  CAS  Google Scholar 

  4. Avramis VI, Panosyan EH. Pharmacokinetic/pharmacodynamic relationships of asparaginase formulations: the past, the present and recommendations for the future. Clin Pharmacokinet. 2005;44(4):367–93. https://doi.org/10.2165/00003088-200544040-00003.

    Article  CAS  Google Scholar 

  5. Moghrabi A, Levy DE, Asselin B, et al. Results of the Dana-Farber Cancer Institute ALL Consortium Protocol 95–01 for children with acute lymphoblastic leukemia. Blood. 2007;109(3):896–904. https://doi.org/10.1182/blood-2006-06-027714.

    Article  CAS  Google Scholar 

  6. Silverman LB, Gelber RD, Dalton VK, et al. Improved outcome for children with acute lymphoblastic leukemia: results of Dana-Farber Consortium Protocol 91–01. Blood. 2001;97(5):1211–8. https://doi.org/10.1182/blood.v97.5.1211.

    Article  CAS  Google Scholar 

  7. Pui CH, Evans WE. Treatment of acute lymphoblastic leukemia. N Engl J Med. 2006;354(2):166–78. https://doi.org/10.1056/NEJMra052603.

    Article  CAS  Google Scholar 

  8. Avramis VI, Sencer S, Periclou AP, et al. A randomized comparison of native Escherichia coli asparaginase and polyethylene glycol conjugated asparaginase for treatment of children with newly diagnosed standard-risk acute lymphoblastic leukemia: a Children’s Cancer Group study. Blood. 2002;99(6):1986–94.

    Article  CAS  Google Scholar 

  9. Zeidan A, Wang ES, Wetzler M. Pegasparaginase: where do we stand? Expert Opin Biol Ther. 2009;9(1):111–9. https://doi.org/10.1517/14712590802586058.

    Article  CAS  Google Scholar 

  10. Angiolillo AL, Schore RJ, Devidas M, et al. Pharmacokinetic and pharmacodynamic properties of calaspargase pegol Escherichia coli l-asparaginase in the treatment of patients with acute lymphoblastic leukemia: results from Children’s Oncology Group Study AALL07P4. J Clin Oncol. 2014;32(34):3874–82.

    Article  CAS  Google Scholar 

  11. European Medicines Agency (EMA). Available at: www.ema.europa.eu/en/medicines/human/EPAR/oncaspar. Accessed 30 June 2020.

  12. Kurtzberg J, Asselin B, Bernstein M, et al. Polyethylene glycol-conjugated l-asparaginase versus native l-asparaginase in combination with standard agents for children with acute lymphoblastic leukemia in second bone marrow relapse: a Children’s Oncology Group Study (POG 8866). J Pediatr Hematol Oncol. 2011;33(8):610–6. https://doi.org/10.1097/MPH.0b013e31822d4d4e.

    Article  CAS  Google Scholar 

  13. Vora A, Goulden N, Mitchell C, et al. Augmented post-remission therapy for a minimal residual disease-defined high-risk subgroup of children and young people with clinical standard-risk and intermediate-risk acute lymphoblastic leukaemia (UKALL 2003): a randomised controlled trial. Lancet Oncol. 2014;15(8):809–18. https://doi.org/10.1016/S1470-2045(14)70243-8.P.

    Article  Google Scholar 

  14. Vora A, Goulden N, Wade R, et al. Treatment reduction for children and young adults with low-risk acute lymphoblastic leukaemia defined by minimal residual disease (UKALL 2003): a randomised controlled trial. Lancet Oncol. 2013;14(3):199–209. https://doi.org/10.1016/S1470-2045(12)70600-9.

    Article  CAS  Google Scholar 

  15. Haithcox S, Ramnes CR, Lee H, et al. The impact of frequent injections for hematopoietic growth factor support on patients receiving chemotherapy: an observational study. BMC Nurs. 2003;2:2.

    Article  Google Scholar 

  16. Place AE, Stevenson KE, Vrooman LM, et al. Intravenous pegylated asparaginase versus intramuscular native Escherichia coli l-asparaginase in newly diagnosed childhood acute lymphoblastic leukaemia (DFCI 05–001): a randomised, open-label phase 3 trial. Lancet Oncol. 2015;16(16):1677–90. https://doi.org/10.1016/s1470-2045(15)00363-0.

    Article  CAS  Google Scholar 

  17. Hu X, Wildman K, Basu S, et al. The cost-effectiveness of pegaspargase versus native asparaginase for first-line treatment of acute lymphoblastic leukaemia: a UK-based cost-utility analysis. Health Econ Rev. 2019;9(1):40.

    Article  Google Scholar 

  18. Gourzoulidis G, Maniadakis N, Petrakis D, et al. Economic evaluation of trifluridine and tipiracil hydrochloride in the treatment of metastatic colorectal cancer in Greece. J Comp Effect Res. 2019;8:133–42. https://doi.org/10.2217/cer-2018-0076.

    Article  Google Scholar 

  19. Vellopoulou K, Stefanou G, Tzanetakos C, et al. Cost-effectiveness of tofacitinib for the treatment of moderate to severe active ulcerative colitis in Greece. Eur J Gastroenterol Hepatol. 2021;33:325–33. https://doi.org/10.1097/meg.0000000000001916.

    Article  CAS  Google Scholar 

  20. National Institute for Health and Care Excellence (NICE). Guide to the methods of technology appraisal. 2013. Available at: https://www.nice.org.uk/process/pmg9/chapter/involvement-and-participation. Accessed 1 Feb 2020.

  21. European Network for Health Technology Assessment (EUnetHTA). Pharmacoeconomic guidelines around the world. May 2015. Available at: https://www.eunethta.eu/wp-content/uploads/2018/03/Methods_for_health_economic_evaluations.pdf. Accessed 10 Jan 2021.

  22. Burke MJ, Devidas M, Maloney K, et al. Severe pegaspargase hypersensitivity reaction rates (grade ≥3) with intravenous infusion vs. intramuscular injection: analysis of 54,280 doses administered to 16,534 patients on children’s oncology group (COG) clinical trials. Leukemia Lymphoma. 2018;59:1624–33.

    Article  CAS  Google Scholar 

  23. Pieters R, Hunger SP, Boos J, et al. l-Asparaginase treatment in acute lymphoblastic leukemia. Cancer. 2011;117:238–49. https://doi.org/10.1002/cncr.25489.

    Article  CAS  Google Scholar 

  24. Vrooman LM, Kirov II, Dreyer ZE, et al. Activity and toxicity of intravenous erwinia asparaginase following allergy to E coli-derived asparaginase in children and adolescents with acute lymphoblastic leukemia. Pediatr Blood Cancer. 2016;63(2):228–33. https://doi.org/10.1002/pbc.25757.

    Article  CAS  Google Scholar 

  25. World Health Organization (WHO). Greece life tables. Available at: http://apps.who.int/gho/data/?theme=main&vid=60640. Accessed 30 June 2020.

  26. Graham ML. Pegaspargase: a review of clinical studies. Adv Drug Deliv Rev. 2003;55:1293–302. https://doi.org/10.1016/S0169-409X(03)00110-8.

    Article  CAS  Google Scholar 

  27. Müller HJ, Boos J. Use of l-asparaginase in childhood ALL. Crit Rev Oncol Hematol. 1998;28:97–113. https://doi.org/10.1016/S1040-8428(98)00015-8.

    Article  Google Scholar 

  28. Burke MJ, Devidas M, Maloney K, et al. Severe pegaspargase hypersensitivity reaction rates (grade ≥3) with intravenous infusion vs. intramuscular injection: analysis of 54,280 doses administered to 16,534 patients on children’s oncology group (COG) clinical trials. Leukemia lymphoma. 2018;59(7):1624–33. https://doi.org/10.1080/10428194.2017.1397658.

    Article  CAS  Google Scholar 

  29. Pieters R, Hunger SP, Boos J, et al. l-Asparaginase treatment in acute lymphoblastic leukemia. Cancer. 2011;117(2):238–49. https://doi.org/10.1002/cncr.25489.

    Article  CAS  Google Scholar 

  30. Szende A, Janssen B, Cabases J. Self-reported population health: an international perspective based on EQ-5D. Available at: https://link.springer.com/chapter/10.1007/978-94-007-7596-1_3. 2014. Accessed 30 June 2020.

  31. Furlong W, Rae C, Feeny D, et al. Health-related quality of life among children with acute lymphoblastic leukemia. Pediatr Blood Cancer. 2012;59:717–24.

    Article  Google Scholar 

  32. National Institute for Health and Clinical Excellence (NICE). NICE clinical guideline 134. Anaphylaxis. Available at: http://www.nice.org.uk/guidance/cg134/evidence/anaphylaxis-full-guideline-184946941. Accessed 1 Feb 2020.

  33. Greek Ministry of Health. Drug price bulletin 2020. Available at: https://www.moh.gov.gr/articles/times-farmakwn/deltia-timwn. Accessed 30 June 2020.

  34. Pharmaceutical Research and Technology company (I.F.E.T.). List of medicines. Available at: https://www.ifet.gr/en/. Accessed 30 June 2020.

  35. Greek Ministry of Health. DRG code: Σ22X. Diagnostic related groups. 2020. Available at: http://kenicd.e-healthnet.gr/KEN%CE%91%CE%BD%CE%B1%CE%BB%CF%85%CF%84%CE%B9%CE%BA%CE%AC.aspx?iditem=%ce%a322%ce%9c. Accessed 30 June 2020.

  36. Greek Ministry of Health. DRG code: Φ61Α. Diagnostic related groups. Available at: http://kenicd.e-healthnet.gr/KEN%CE%91%CE%BD%CE%B1%CE%BB%CF%85%CF%84%CE%B9%CE%BA%CE%AC.aspx?iditem=%ce%a661%ce%91. Accessed 30 June 2020.

  37. Greek Ministry of Health. DRG code: Ρ22Μ. Diagnostic related groups. Available at: http://kenicd.e-healthnet.gr/KEN%CE%91%CE%BD%CE%B1%CE%BB%CF%85%CF%84%CE%B9%CE%BA%CE%AC.aspx?iditem=%ce%a122%ce%9c. Accessed 30 June 2020.

  38. Gourzoulidis G, Vassilopoulos G, Gialama F, et al. Economic evaluation of dasatinib compared to nilotinib as second line treatment of chronic myeloid leukemia in Greece. Value Health. 2017;20(9):PA443.

    Article  Google Scholar 

  39. National Organization for Healthcare Services Provision (EOPYY). Available at: https://www.eopyy.gov.gr/. Accessed 30 June 2020.

  40. Woods B, Revill P, Sculpher M, et al. Country-level cost-effectiveness thresholds: initial estimates and the need for further research. Value Health. 2016;19:929–35. https://doi.org/10.1016/j.jval.2016.02.017.

    Article  Google Scholar 

  41. Thokala P, Ochalek J, Leech AA, et al. Cost-effectiveness thresholds: the past, the present and the future. Pharmacoeconomics. 2018;36:509–22. https://doi.org/10.1007/s40273-017-0606-1.

    Article  Google Scholar 

  42. Cameron D, Ubels J, Norström F. On what basis are medical cost-effectiveness thresholds set? Clashing opinions and an absence of data: a systematic review. Glob Health Action. 2018;11(1):1447828. https://doi.org/10.1080/16549716.2018.1447828.

    Article  Google Scholar 

  43. Tzanetakos C, Stefanou G, Gourzoulidis G. PNS61 does a standard willingness-to-pay threshold exist in Greece? Value Health. 2019;22(Suppl 3):S772–3. https://doi.org/10.1016/j.jval.2019.09.1963.

    Article  Google Scholar 

  44. International Monetary Fund. World Economic Outlook Database 2020. Available at: https://www.imf.org/external/pubs/ft/weo/2019/02/weodata/index.aspx. Accessed 30 June 2020

  45. Tong WH, van der Sluis IM, Alleman CJ, et al. Cost-analysis of treatment of childhood acute lymphoblastic leukemia with asparaginase preparations: the impact of expensive chemotherapy. Haematologica. 2013;98(5):753–9. https://doi.org/10.3324/haematol.2012.073510.

    Article  Google Scholar 

  46. Kurre HA, Ettinger AG, Veenstra DL, et al. A pharmacoeconomic analysis of pegaspargase versus native Escherichia coli l-asparaginase for the treatment of children with standard-risk, acute lymphoblastic leukemia: the Children’s Cancer Group study (CCG-1962). J Pediatr Hematol Oncol. 2002;24(3):175–81. https://doi.org/10.1097/00043426-200203000-00004.

    Article  Google Scholar 

  47. Peters BG, Goeckner BJ, Ponzillo JJ, et al. Pegaspargase versus asparaginase in adult ALL: a pharmacoeconomic assessment. Formulary. 1995;30(7):388–93.

    CAS  Google Scholar 

Download references

Acknowledgements

The authors would like to thank Servier Hellas for funding this research.

Author information

Authors and Affiliations

  1. ECONCARE LP, Athens, Greece

    George Gourzoulidis, Maria Koulentaki & Georgia Kourlaba

  2. First Department of Pediatrics, National and Kapodistrian University of Athens, “Aghia Sophia” Children’s Hospital, Athens, Greece

    Antonis Kattamis

  3. Hematology and Lymphoma Department, “Evangelismos” Athens General Hospital, Athens, Greece

    Maria Bouzani & Chara Giatra

  4. Servier Hellas Pharmaceuticals Ltd, Athens, Greece

    Vassiliki Chotzagiannoglou & Alexandra Beletsi

Authors
  1. George Gourzoulidis
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Maria Koulentaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Antonis Kattamis
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Maria Bouzani
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Chara Giatra
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Vassiliki Chotzagiannoglou
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Alexandra Beletsi
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Georgia Kourlaba
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to George Gourzoulidis.

Ethics declarations

Conflict of interest

Econcare LP received research grant funding from Servier Hellas. AB and VC were Servier Hellas employees at the time of this study. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript, apart from those disclosed.

Funding

This study was sponsored by Servier Hellas. The study sponsor had no interference in the study design, data collection, or writing of the manuscript.

Ethical approval

This study was an economic evaluation analysis and does not involve human subjects. Input data including human material or human data derived from other published studies was performed with the approval of an appropriate Ethics Committee; therefore, ethics approval was not required for the performance of this cost-effectiveness analysis.

Consent to publish

Not applicable.

Consent to participate

Not applicable.

Code availability

Not applicable.

Availability of data and materials

All data used to conduct this study are included in this published article.

Author contributions

GG and MK conducted the analyses, collected the data, and interpreted the results. GG wrote the manuscript. AK, MB, and CG were the local clinical experts who provided local resource utilization data and contributed to data validation and interpretation of the results. VC, AB, and GK contributed to interpretation of the results and manuscript writing. All authors reviewed and approved the final version of the manuscript.

Additional information

The original online version of this article was revised: All authors’ first and last names have been swapped.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 44 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gourzoulidis, G., Koulentaki, M., Kattamis, A. et al. Cost-Utility Analysis of Pegaspargase for the Treatment of Acute Lymphoblastic Leukemia in Greece. Clin Drug Investig 42, 999–1008 (2022). https://doi.org/10.1007/s40261-022-01207-w

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40261-022-01207-w

Search

Navigation