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Open Access 12-01-2023 | Paroxysmal Nocturnal Hemoglobinuria | Original Paper

Cost-effectiveness of ravulizumab compared with eculizumab for the treatment of paroxysmal nocturnal hemoglobinuria in the Netherlands

Authors: S. W. Quist, A. J. Postma, K. J. Myrén, L. A. de Jong, M. J. Postma

Published in: The European Journal of Health Economics | Issue 9/2023

Abstract

Objectives

The aim of this study was to evaluate the cost-effectiveness of ravulizumab compared with eculizumab for the treatment of adult patients with paroxysmal nocturnal hemoglobinuria (PNH) in the Netherlands.

Methods

A cost-effectiveness analysis was conducted based on a Markov cohort model simulating the course of patients with PNH with clinical symptom(s) indicative of high disease activity, or who are clinically stable after having been treated with eculizumab for at least the past six months. Costs, quality of life, and the incremental cost-effectiveness ratio (ICER) were estimated over a lifetime horizon from a Dutch societal perspective. Several additional analyses were performed, including a one-way sensitivity analysis, a probabilistic sensitivity analysis, and scenario analysis.

Results

When compared with eculizumab, ravulizumab saves €266,833 and 1.57 quality adjusted life years (QALYs) are gained, resulting in a dominant ICER. Drug costs account for the majority of the total costs in both intervention groups. Cost savings were driven by the difference in total treatment costs of ravulizumab compared with eculizumab caused by the reduced administration frequency, accounting for 98% of the total cost savings. The QALY gain with ravulizumab is largely attributable to the improved quality of life associated with less frequent infusions and BTH events. At a willingness-to-pay threshold of €20,000/QALY, there is a 76.6% probability that ravulizumab would be cost-effective.

Conclusions

The cost reduction and QALY gain associated with the lower rates of BTH and less frequent administration make ravulizumab a cost-saving and clinically beneficial substitute for eculizumab for adults with PNH in the Netherlands.

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Schrezenmeier, H., Muus, P., Socié, G., Szer, J., Urbano-Ispizua, A., Maciejewski, J.P., Brodsky, R.A., Bessler, M., Kanakura, Y., Rosse, W., Khursigara, G., Bedrosian, C., Hillmen, P.: Baseline characteristics and disease burden in patients in the International Paroxysmal Nocturnal Hemoglobinuria Registry. Haematologica 99, 922–929 (2014). https://doi.org/10.3324/HAEMATOL.2013.093161CrossRefPubMedPubMedCentral

Weitz, I., Meyers, G., Lamy, T., Cahn, J.Y., Uranga, M.T., García Vela, J.A., Sanz, M.A., Severino, B., Kelly, R.J., Hillmen, P., Hill, A.: Cross-sectional validation study of patient-reported outcomes in patients with paroxysmal nocturnal haemoglobinuria. Intern. Med. J. 43, 298–307 (2013). https://doi.org/10.1111/J.1445-5994.2012.02924.XCrossRefPubMed

Muus, P., Langemeijer, S., Halkes, S., Zeerleder, S., Schouten, H., Boekhorst te, P., Span, B., Witte de, M., Bartels, M., Jansen, A., Stiene, A., Preijers, F., Pampus van, L., Evers, D., Nijziel, M., Laros, B., Heijden van der, O.: Guideline for Paroxysmal Nocturnal Hemoglobinuria (Dutch: Richtlijn Paroxysmale Nachtelijke Hemoglobinurie), Nijmegen (2016). https://hematologienederland.nl/wp-content/uploads/2019/07/Richtlijn-PNH-2016_def.pdf

Hill, A., Platts, P.J., Smith, A., Richards, S.J., Cullen, M.J., Hill, Q.A., Roman, E., Hillmen, P.: The incidence and prevalence of Paroxysmal Nocturnal Hemoglobinuria (PNH) and survival of patients in yorkshire. Blood 108, 985–985 (2006). https://doi.org/10.1182/BLOOD.V108.11.985.985CrossRef

Dutch Statistics: Population count (Dutch: Bevolkingsteller), Netherlands (2022). https://www.cbs.nl/nl-nl/visualisaties/dashboard-bevolking/bevolkingsteller

Röth, A., Araten, D.J., Larratt, L., Kulasekararaj, A.G., Maciejewski, J.P., Wilson, A., Gustovic, P., Kanakura, Y.: Beneficial effects of eculizumab regardless of prior transfusions or bone marrow disease: Results of the International Paroxysmal Nocturnal Hemoglobinuria Registry. Eur J Haematol. 105, 561–570 (2020). https://doi.org/10.1111/EJH.13485CrossRefPubMed

Alexion AstraZeneca Rare Disease, internal data PNH register (2021)

Hillmen, P., Lewis, S.M., Bessler, M., Luzzatto, L., Dacie, J.: Natural history of paroxysmal nocturnal hemoglobinuria. N. Engl. J. Med. 333, 1253–1258 (1995). https://doi.org/10.1056/NEJM199511093331904CrossRefPubMed

Korkama, E.S., Armstrong, A.E., Jarva, H., Meri, S.: Spontaneous remission in paroxysmal nocturnal hemoglobinuria-return to health or transition into malignancy? Front. Immunol. (2018). https://doi.org/10.3389/FIMMU.2018.01749CrossRefPubMedPubMedCentral

10.

Kelly, R.J., Hill, A., Arnold, L.M., Brooksbank, G.L., Richards, S.J., Cullen, M., Mitchell, L.D., Cohen, D.R., Gregory, W.M., Hillmen, P.: Long-term treatment with eculizumab in paroxysmal nocturnal hemoglobinuria: sustained efficacy and improved survival. Blood 117, 6786–6792 (2011). https://doi.org/10.1182/BLOOD-2011-02-333997CrossRefPubMed

11.

Brodsky, R.A.: Paroxysmal nocturnal hemoglobinuria. Blood 124, 2804–2811 (2014). https://doi.org/10.1182/BLOOD-2014-02-522128CrossRefPubMedPubMedCentral

12.

Almeida, A.M., Bedrosian, C., Cole, A., Muus, P., Schrezenmeier, H., Szer, J., Rosse, W.F.: Clinical benefit of eculizumab in patients with no transfusion history in the International Paroxysmal Nocturnal Haemoglobinuria Registry. Intern. Med. J. 47, 1026–1034 (2017). https://doi.org/10.1111/IMJ.13523CrossRefPubMed

13.

Muus, P., Langemeijer, S., Hochsmann, B., Hill, A., Arnold, L., Tjonnfjord, G., Donato, B., Gustovic, P., Wilson, A., Szer, J.: Patient-reported outcomes and healthcare resource utilization before and during treatment with eculizumab: results from the international paroxysmal nocturnal hemoglobinuria registry. Haematologica 102, 125–126 (2017)

14.

European Medicines Agency (EMA): Summary of Product Characteristics. Soliris (2019)

15.

European Medicines Agency (EMA): Summary of Product Characteristics: Ultomiris (2019)

16.

Levy, A.R., Dysart, L., Patel, Y., Briggs, A., Schneider, J., Myren, K.-J., Tomazos, I.: Comparison of lost productivity due to Eculizumab and Ravulizumab treatments for paroxysmal nocturnal hemoglobinuria in France, Germany, Italy, Russia, Spain, the United Kingdom, and the United States. Blood 134, 4803–4803 (2019). https://doi.org/10.1182/BLOOD-2019-127443CrossRef

17.

Groth, M., Singer, S., Niedeggen, C., Petermann-Meyer, A., Röth, A., Schrezenmeier, H., Höchsmann, B., Brümmendorf, T.H., Panse, J.: Development of a disease-specific quality of life questionnaire for patients with aplastic anemia and/or paroxysmal nocturnal hemoglobinuria (QLQ-AA/PNH)-report on phases I and II. Ann. Hematol. 96, 171–181 (2017). https://doi.org/10.1007/S00277-016-2867-8CrossRefPubMed

18.

Ardissino, G., Testa, S., Possenti, I., Tel, F., Paglialonga, F., Salardi, S., Tedeschi, S., Belingheri, M., Cugno, M.: Discontinuation of eculizumab maintenance treatment for atypical hemolytic uremic syndrome: a report of 10 cases. Am. J. Kidney Dis. 64, 633–637 (2014). https://doi.org/10.1053/J.AJKD.2014.01.434CrossRefPubMed

19.

European Medicines Agency (EMA): EPAR Ultomiris (2019)

20.

Lee, J.W., de Fontbrune, F.S., Lee, L.W.L., Pessoa, V., Gualandro, S., Füreder, W., Ptushkin, V., Rottinghaus, S.T., Volles, L., Shafner, L., Aguzzi, R., Pradhan, R., Schrezenmeier, H., Hill, A.: Ravulizumab (ALXN1210) vs eculizumab in adult patients with PNH naive to complement inhibitors: the 301 study. Blood 133, 530–539 (2019). https://doi.org/10.1182/BLOOD-2018-09-876136CrossRefPubMedPubMedCentral

21.

Röth, A., Rottinghaus, S.T., Hill, A., Bachman, E.S., Kim, J.S., Schrezenmeier, H., Terriou, L., Urbano-Ispizua, Á., Wells, R.A., Jang, J.H., Kulasekararaj, A.G., Szer, J., Aguzzi, R., Damokosh, A.I., Shafner, L., Lee, J.W.: Ravulizumab (ALXN1210) in patients with paroxysmal nocturnal hemoglobinuria: results of 2 phase 1b/2 studies. Blood Adv. 2, 2176–2185 (2018). https://doi.org/10.1182/BLOODADVANCES.2018020644CrossRefPubMedPubMedCentral

22.

Kulasekararaj, A.G., Hill, A., Rottinghaus, S.T., Langemeijer, S., Wells, R., Gonzalez-Fernandez, F.A., Gaya, A., Lee, J.W., Gutierrez, E.O., Piatek, C.I., Szer, J., Risitano, A., Nakao, S., Bachman, E., Shafner, L., Damokosh, A.I., Ortiz, S., Röth, A., Peffault de Latour, R.: Ravulizumab (ALXN1210) vs eculizumab in C5-inhibitor-experienced adult patients with PNH: the 302 study. Blood 133, 540–549 (2019). https://doi.org/10.1182/BLOOD-2018-09-876805CrossRefPubMedPubMedCentral

23.

National Institute for Health and Care Excellence (NICE): Ravulizumab for treating paroxysmal nocturnal haemoglobinuria [ID1457].

24.

SMC: ravulizumab 300mg/30mL concentrate for solution for infusion (Ultomiris®) (2021). https://www.scottishmedicines.org.uk/media/5756/ravulizumab-ultomiris-final-jan-2021-for-website.pdf

25.

Husereau, D., Drummond, M., Petrou, S., Carswell, C., Moher, D., Greenberg, D., Augustovski, F., Briggs, A.H., Mauskopf, J., Loder, E.: Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement. Value Health. 16, e1 (2013). https://doi.org/10.1016/J.JVAL.2013.02.010CrossRefPubMed

26.

Versteegh, M.M., Ramos, I.C., Buyukkaramikli, N.C., Ansaripour, A., Reckers-Droog, V.T., Brouwer, W.B.F.: Severity-adjusted probability of being cost effective. Pharmacoeconomics 37, 1155–1163 (2019). https://doi.org/10.1007/S40273-019-00810-8CrossRefPubMedPubMedCentral

27.

Dutch Institute National Health Care (Zorginstituut Nederland): Guideline for economic evaluations in healthcare | Guideline | National Health Care Institute. , Diemen (2016)

28.

Alexion Pharmaceuticals Internal Communication Rottinghaus ST. , (2018)

29.

Dutch Statistics: StatLine - Length and weight data from 1981 (Dutch: Lengte en gewicht van personen, ondergewicht en overgewicht; vanaf 1981) (2021) https://www.cbs.nl/nl-nl/cijfers/detail/81565NED?dl=35805

30.

Newton, D.J., McKinley, C.E., Ricardo, A., Hoarty, M.D., Arnold, L., Riley, K., Copeland, N., Munir, T., Griffin, M., Hill, A., Hillmen, P.: Assessment of Eculizumab and C5 Levels in PNH treatment: molar ratio of Eculizumab to C5 level effectively predicts ongoing dosage changes in a cohort of 50 patients treated with Eculizumab. Blood 130, 3484–3484 (2017). https://doi.org/10.1182/BLOOD.V130.SUPPL_1.3484.3484CrossRef

31.

Dutch Statistics: StatLine - Life expectancy; sex, age (per year and period of five years) (Dutch: Levensverwachting; geslacht, leeftijd (per jaar en periode van vijf jaren) (2021). https://www.cbs.nl/nl-nl/cijfers/detail/37360ned?q=levensverwachting%20geslacht%20leeftijd%20per%20jaar%20en%20periode%20van%20vijf%20jaren

32.

Jang, J.H., Kim, J.S., Yoon, S.S., Lee, J.H., Kim, Y.K., Jo, D.Y., Chung, J., Sohn, S.K., Lee, J.W.: Predictive factors of mortality in population of patients with Paroxysmal Nocturnal Hemoglobinuria (PNH): Results from a Korean PNH Registry. J Korean Med Sci. 31, 214–221 (2016). https://doi.org/10.3346/JKMS.2016.31.2.214CrossRefPubMedPubMedCentral

33.

Versteegh, M.M., Leunis, A., Luime, J.J., Boggild, M., Uyl-De Groot, C.A., Stolk, E.A.: Mapping QLQ-C30, HAQ, and MSIS-29 on EQ-5D. Med. Decis. Mak. 32, 554–568 (2012). https://doi.org/10.1177/0272989X11427761CrossRef

34.

Longworth, L., Rowen, D.: Mapping to obtain EQ-5D utility values for use in NICE health technology assessments. Value Health. 16, 202–210 (2013). https://doi.org/10.1016/J.JVAL.2012.10.010CrossRefPubMed

35.

Dychter, S.S., Gold, D.A., Carson, D., Haller, M.: Intravenous therapy: a review of complications and economic considerations of peripheral access. J. Infus. Nurs. 35, 84–91 (2012). https://doi.org/10.1097/NAN.0B013E31824237CECrossRefPubMed

36.

O’Connell, T., Buessing, M., Johnson, S., Tu, L., Thomas, S.K., Tomazos, I.: Cost-utility analysis of ravulizumab compared with eculizumab in adult patients with paroxysmal nocturnal hemoglobinuria. Pharmacoeconomics 38, 981–994 (2020). https://doi.org/10.1007/S40273-020-00929-ZCrossRefPubMed

37.

Lloyd, A.J., Gallop, K., Ali, S., Myren, K.J., Sierra, J.R., Anokhina, K., Patriquin, C., Hill, A., Tomazos, I.: PSY9 preference weights for quality-adjusted life-years estimation for treatments of paroxysmal nocturnal hemoglobinuria in the United Kingdom. Value Health 22, S902 (2019). https://doi.org/10.1016/j.jval.2019.09.2637CrossRef

38.

Lloyd, A.J., Gallop, K., Ali, S., Myren, K.J., Sierra, J.R., Anokhina, K., Patriquin, C., Hill, A., Tomazos, I.: PRO32 preference weights for quality-adjusted life-years estimation for treatments of paroxysmal nocturnal hemoglobinuria in five COUNTRIES. Value Health 23, S334 (2020). https://doi.org/10.1016/j.jval.2020.04.1260CrossRef

39.

Janssen, M.F., Szende, A., Cabases, J., Ramos-Goñi, J.M., Vilagut, G., König, H.H.: Population norms for the EQ-5D-3L: a cross-country analysis of population surveys for 20 countries. Eur. J. Health Econ. 20, 205–216 (2019). https://doi.org/10.1007/S10198-018-0955-5CrossRefPubMed

40.

Dutch Statistics: StatLine - Annual change in consumer price index; from 1963 (Jaarmutatie consumentenprijsindex; vanaf 1963) (2021). https://opendata.cbs.nl/statline/#/CBS/nl/dataset/70936ned/table?ts=15210215976

41.

Dutch Healthcare Authority (Dutch: Nederlandse Zorgautoriteit) (NZa): DIS open data - DBC codes (2021). https://www.opendisdata.nl/

42.

Tomazos, I., Sierra, J.R., Johnston, K.M., Cheung, A., Brodsky, R.A., Weitz, I.C.: Cost burden of breakthrough hemolysis in patients with paroxysmal nocturnal hemoglobinuria receiving ravulizumab versus eculizumab. Hematology 25, 327–334 (2020). https://doi.org/10.1080/16078454.2020.1807226CrossRefPubMed

43.

Hakkaart-van Roijen, L., van der Linden, N., Bouwmans, C., Kanters, T., Swan Tan, S.: Cost Manual: Methodology and Reference Prices for Healthcare Economic Evaluations. (Dutch: Kostenhandleiding: Methodologie van kostenonderzoek en referentieprijzen voor economische evaluaties in de gezondheidszorg. , Diemen (2016)

44.

Dutch Institute National Health Care (Zorginstituut Nederland): Medicijnkosten.nl, https://www.medicijnkosten.nl/

45.

Dutch Statistics: StatLine - Labour participation (Dutch: Arbeidsdeelname; kerncijfers.), https://www.cbs.nl/nl-nl/cijfers/detail/82309NED

46.

Brodsky, R.A., de Latour, R.P., Rottinghaus, S.T., Röth, A., Risitano, A.M., Weitz, I.C., Hillmen, P., MacIejewski, J.P., Szer, J., Lee, J.W., Kulasekararaj, A.G., Volles, L., Damokosh, A.I., Ortiz, S., Shafner, L., Liu, P., Hill, A., Schrezenmeier, H.: Characterization of breakthrough hemolysis events observed in the phase 3 randomized studies of ravulizumab versus eculizumab in adults with paroxysmal nocturnal hemoglobinuria. Haematologica 106, 230–237 (2021). https://doi.org/10.3324/HAEMATOL.2019.236877CrossRefPubMed

47.

Kulasekararaj, A., Hill, A., Langemeijer, S., Wells, R.A., Gonzalez-Fernandez, F.A., Gaya, A., Ojeda Gutierrez, E., Piatek, C.I., Mitchell, L.D., Usuki, K., Bosi, A., Brodsky, R.A., Ogawa, M., Yu, J., Ortiz, S., Röth, A., Lee, J.-W., Peffault de Latour, R.: One-year efficacy and safety from a phase 3 trial of Ravulizumab in adult patients with paroxysmal nocturnal hemoglobinuria receiving prior Eculizumab treatment. Blood 134, 2231–2231 (2019). https://doi.org/10.1182/BLOOD-2019-128746CrossRef

48.

Schrezenmeier, H., Kulasekararaj, A., Mitchell, L., Sicre de Fontbrune, F., Devos, T., Okamoto, S., Wells, R., Rottinghaus, S.T., Liu, P., Ortiz, S., Lee, J.W., Socié, G.: One-year efficacy and safety of ravulizumab in adults with paroxysmal nocturnal hemoglobinuria naïve to complement inhibitor therapy: open-label extension of a randomized study. Ther. Adv. Hematol. (2020). https://doi.org/10.1177/2040620720966137CrossRefPubMedPubMedCentral

49.

Kulasekarara, A., Griffin, M., Langemeijer, S., Usuki, K., Kulagin, A., Ogawa, M., Yu, J., Mujeebuddin, A., Nishimura, J., Wook Lee, J., Peffault de Latuur, R.: Safety of ravulizumab in patients with paroxysmal nocturnal hemoglobinuria: study 301/302 2-year results EHA Library. Peffault de Latour R. Jun 9 2021; 325354. EHA. 6–9 (2021)

50.

Hillmen, P., Muus, P., Röth, A., Elebute, M.O., Risitano, A.M., Schrezenmeier, H., Szer, J., Browne, P., Maciejewski, J.P., Schubert, J., Urbano-Ispizua, A., de Castro, C., Socié, G., Brodsky, R.A.: Long-term safety and efficacy of sustained eculizumab treatment in patients with paroxysmal nocturnal haemoglobinuria. Br. J. Haematol. 162, 62–73 (2013). https://doi.org/10.1111/BJH.12347CrossRefPubMedPubMedCentral

51.

Franken, M., Kanters, T., Coenen, J., de Jong, P., Jager, A., de Groot, C.U.: Hospital-based or home-based administration of oncology drugs? A micro-costing study comparing healthcare and societal costs of hospital-based and home-based subcutaneous administration of trastuzumab. Breast 52, 71–77 (2020). https://doi.org/10.1016/J.BREAST.2020.05.001CrossRefPubMedPubMedCentral

52.

Levy, A.R., Tomazos, I., Patel, Y., Donato, B.M.K., Briggs, A.: PSY15 comparison of lost productivity due to eculizumab and ravulizumab treatments for paroxysmal nocturnal hemoglobinuria in the United States. Value Health 22, S377 (2019). https://doi.org/10.1016/j.jval.2019.04.1840CrossRef

53.

Niedeggen, C., Singer, S., Groth, M., Petermann-Meyer, A., Röth, A., Schrezenmeier, H., Höchsmann, B., Brümmendorf, T.H., Panse, J.: Design and development of a disease-specific quality of life tool for patients with aplastic anaemia and/or paroxysmal nocturnal haemoglobinuria (QLQ-AA/PNH)-a report on phase III. Ann Hematol 98, 1547–1559 (2019). https://doi.org/10.1007/S00277-019-03681-3CrossRefPubMedPubMedCentral

54.

Peipert, J.D., Kulasekararaj, A.G., Gaya, A., Langemeijer, S.M.C., Yount, S., Gonzalez-Fernandez, F.A., Gutierrez, E.O., Martens, C., Sparling, A., Webster, K.A., Cella, D., Tomazos, I., Ogawa, M., Piatek, C.I., Wells, R., de Fontbrune, F.S., Röth, A., Mitchell, L., Hill, A., Kaiser, K.: Patient preferences and quality of life implications of ravulizumab (every 8 weeks) and eculizumab (every 2 weeks) for the treatment of paroxysmal nocturnal hemoglobinuria. PLoS One 15, e0237497 (2020). https://doi.org/10.1371/JOURNAL.PONE.0237497CrossRefPubMedPubMedCentral

Title: Cost-effectiveness of ravulizumab compared with eculizumab for the treatment of paroxysmal nocturnal hemoglobinuria in the Netherlands
Authors: S. W. Quist
A. J. Postma
K. J. Myrén
L. A. de Jong
M. J. Postma
Publication date: 12-01-2023
Publisher: Springer Berlin Heidelberg
Keyword: Paroxysmal Nocturnal Hemoglobinuria
Published in: The European Journal of Health Economics / Issue 9/2023
Print ISSN: 1618-7598
Electronic ISSN: 1618-7601
DOI: https://doi.org/10.1007/s10198-022-01556-5

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Cost-effectiveness of ravulizumab compared with eculizumab for the treatment of paroxysmal nocturnal hemoglobinuria in the Netherlands

Abstract

Objectives

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Objectives

Methods

Results

Conclusions

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