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Direct and Indirect Costs of Immunoglobulin Replacement Therapy in Patients with Common Variable Immunodeficiency (CVID) and X-Linked Agammaglobulinemia (XLA) in Italy

Clinical Drug Investigation volume 38, pages 955–965 (2018)Cite this article

Abstract

Background

In Italy, there is scarce evidence on the epidemiological and economic burden induced by primary antibody deficiencies.

Objective

The aim of this study was to elaborate the available epidemiological and cost data in order to estimate the annual expenditure induced by the management of patients affected by the common variable immunodeficiency (CVID) and X-linked agammaglobulinemia (XLA) requiring immunoglobulin (Ig) replacement therapy.

Methods

A probabilistic cost-of-illness model was developed to estimate the number of patients with CVID and XLA, and the economic burden associated with their therapy in terms of direct or indirect costs. A systematic literature review was carried out to reveal both epidemiological and economic data. Furthermore, a probabilistic sensitivity analysis with 5000 Monte Carlo simulations was performed.

Results

The epidemiological model allowed us to estimate the number of prevalent patients affected by XLA and CVID in Italy in 2017, corresponding to 1885 (95% confidence interval [CI] 944–3145) and 133 (95% CI 115–152) patients, respectively. The estimated total expenditure for the treatment and management of patients with CVID and XLA requiring Ig replacement therapy amounts to €42.68 million (95% CI €14.38–€86.1 million).

Conclusions

This information provides a comprehensive perspective of the economic issues, and facilitates better-informed public health decision making, in the management of CVID and XLA in Italy.

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References

  1. Driessen G, van der Burg M. Educational paper: primary antibody deficiencies. Eur J Pediatr. 2011;170(6):693–702.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Stonebraker JS, et al. Modeling primary immunodeficiency disease epidemiology and its treatment to estimate latent therapeutic demand for immunoglobulin. J Clin Immunol. 2014;34(2):233–44.

    CAS  Article  PubMed  Google Scholar 

  3. Shehata N, et al. The use of immunoglobulin therapy for patients with primary immune deficiency: an evidence-based practice guideline. Transfus Med Rev. 2010;24(Suppl 1):S28–50.

    Article  PubMed  Google Scholar 

  4. Quinti IB, Barilaro G. Le immunoglobuline per uso endovenoso: efficacia, tollerabilità e consumo. Rivista di Immunologia e Allergologia Pediatrica. 2013;5:28–36.

    Google Scholar 

  5. Kerr J, et al. Is dosing of therapeutic immunoglobulins optimal? A review of a three-decade long debate in Europe. Front Immunol. 2014;5:629.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. European Primary Immunodeficiencies Consensus Conference, Consensus Report and Recommendations, in European Primary Immunodeficiencies Consensus Conference. 19–20 June 2006: Paul-Ehrlich-Institut, Langen, Germany.

  7. Berger M. Subcutaneous immunoglobulin replacement in primary immunodeficiencies. Clin Immunol. 2004;112(1):1–7.

    CAS  Article  PubMed  Google Scholar 

  8. Berger M. Subcutaneous administration of IgG. Immunol Allergy Clin North Am. 2008;28(4):779–802, viii.

    Article  PubMed  Google Scholar 

  9. Bonilla FA. Intravenous immunoglobulin: adverse reactions and management. J Allergy Clin Immunol. 2008;122(6):1238–9.

    Article  PubMed  Google Scholar 

  10. Wasserman RL. Subcutaneous immunoglobulin: facilitated infusion and advances in administration. Clin Exp Immunol. 2014;178(Suppl 1):75–7.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Matucci A, et al. Analisi di minimizzazione dei costi della terapia con Immunoglobuline (Ig) per il trattamento di pazienti con immunodeficienza primaria: confronto tra terapia con Ig sottocute vs endovena. Giornale Italiano di Health Technology Assessment. 2008;1(1):31–7.

    Article  Google Scholar 

  12. Grimbacher B. ESID Registry Working Party, The European Society for Immunodeficiencies (ESID) registry 2014. Clin Exp Immunol. 2014;178(Suppl 1):18–20.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Angelis A, Tordrup D, Kanavos P. Socio-economic burden of rare diseases: a systematic review of cost of illness evidence. Health Policy. 2015;119(7):964–79.

    Article  PubMed  Google Scholar 

  14. Mazzucato M, et al. A population-based registry as a source of health indicators for rare diseases: the ten-year experience of the Veneto Region’s rare diseases registry. Orphanet J Rare Dis. 2014;9:37.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Hodgson TA, Meiners MR. Cost of illness methodology: a guide to current practices and procedures. Milbank Memor Fund Q. 1982;60(3):429–62.

    CAS  Article  Google Scholar 

  16. Berger ML, et al. Cost of Illness Study. In: Bingefors K, Pashos CL, Dix Smith M, Berger ML, Hedblom EC, Torrance GW, editors. Health care cost, quality, and outcomes: ISPOR book of terms. Lawrenceville: ISPOR; 2003. p. 43–4.

    Google Scholar 

  17. Segel JE. Cost-of-illness studies—a primer. RTI-UNC Center of Excellence in Health Promotion Economics; 2006.

  18. Green S, Higgins J. Cochrane handbook for systematic reviews of interventions 4.2.5. The Cochrane Collaboration 2005. 19 May 2009. http://www.cochrane.org/resources/glossary.htm. Accessed 31 Jul 2018.

  19. Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA STATEMENT. PLoS Med. 2009;6(7):e1000097.

    Article  PubMed  PubMed Central  Google Scholar 

  20. CEREDIH: The French PID Study Group. The French national registry of primary immunodeficiency diseases. Clin Immunol. 2010;135(2):264–72.

  21. Edgar JD, et al. The United Kingdom Primary Immune Deficiency (UKPID) Registry: report of the first 4 years’ activity 2008-2012. Clin Exp Immunol. 2014;175(1):68–78.

    CAS  Article  PubMed  Google Scholar 

  22. Kobrynski L, Powell RW, Bowen S. Prevalence and morbidity of primary immunodeficiency diseases, United States 2001–2007. J Clin Immunol. 2014;34(8):954–61.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Gathmann B, et al. The European internet-based patient and research database for primary immunodeficiencies: results 2006-2008. Clin Exp Immunol. 2009;157(Suppl 1):3–11.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Calizzani G, et al. Analisi della domanda dei principali medicinali plasmaderivati in Italia. Anni 2007–2011. Rapporto ISTISAN 2012, Isituto Superiore di Sanità. p. 167.

  25. Quinti I, et al. Effectiveness of immunoglobulin replacement therapy on clinical outcome in patients with primary antibody deficiencies: results from a multicenter prospective cohort study. J Clin Immunol. 2011;31(3):315–22.

    CAS  Article  PubMed  Google Scholar 

  26. Istituto Nazionale di Statistica. Rivalutazione e documentazione su prezzi, costi e retribuzioni contrattuali. Indice dei prezzi al consumo per famiglie operai e impiegati. Novembre 2013. http://rivaluta.istat.it/. Accessed 31 Jul 2018.

  27. Gazzetta Ufficiale della Repubblica Italiana. Regime di rimborsabilità e prezzo di vendita di nuove confezioni dei medicinali. 2015. http://www.gazzettaufficiale.it. Accessed 31 Jul 2018.

  28. Farmadati Italia. Banca Dati Online [cited May 2016]. http://www.farmadati.it/default.aspx. Accessed 31 Jul 2018.

  29. Berger M. Adverse effects of IgG therapy. J Allergy Clin Immunol Pract. 2013;1(6):558–66.

    Article  PubMed  Google Scholar 

  30. EUROSTAT. Hourly labour costs by NACE Rev. 1.1 activity. 2004. http://appsso.eurostat.ec.europa.eu/nui/show.do?dataset=lc_an_costh&lang=en. Accessed 31 Jul 2018.

  31. Briggs A, Claxton K, Sculpher M. Decision modelling for health economic evaluation. New York; O.U.P. Inc.; 2007.

  32. Stewart WF, et al. Cost of lost productive work time among US workers with depression. JAMA. 2003;289(23):3135–44.

    Article  PubMed  Google Scholar 

  33. Hemp P. Presenteeism: at work—but out of it. Harv Bus Rev. 2004;82(10):49–58, 155.

  34. Capone A, et al. Health Data Entanglement and artificial intelligence-based analysis: a brand new methodology to improve the effectiveness of healthcare services. Clin Ter. 2016;167(5):e102–11.

    CAS  PubMed  Google Scholar 

  35. Mahlaoui N, et al. The European Society for Immunodeficiencies (ESID) Registry: recent advancements in the epidemiology of Primary Immunodeficiencies and how does that translate in clinical care. Rare Diseases and Orphan Drugs. 2014;1(4):25–7.

    Google Scholar 

  36. Wasserman RL, et al. Recombinant human hyaluronidase-facilitated subcutaneous infusion of human immunoglobulins for primary immunodeficiency. J Allergy Clin Immunol. 2012;130(4):951–7.e11.

    Article  CAS  Google Scholar 

  37. Baio G, et al. Economic burden of human papillomavirus-related diseases in Italy. PLoS One. 2012;7(11):e49699.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  38. Marcellusi A, et al. The economic burden of HCV-induced diseases in Italy. A probabilistic cost of illness model. Eur Rev Med Pharmacol Sci. 2015;19(9):1610–20.

    CAS  PubMed  Google Scholar 

  39. Stiehm ER. Adverse effects of human immunoglobulin therapy. Transfus Med Rev. 2013;27(3):171–8.

    Article  PubMed  Google Scholar 

  40. Istituto Nazionale di Statistica. ISTAT. 2017 [cited 2017; Italian employment rate]. http://www.istat.it/it/. Accessed 31 Jul 2018.

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Affiliations

  1. Economic Evaluation and HTA (EEHTA), CEIS, Faculty of Economics, University of Rome “Tor Vergata”, Rome, Italy

    Raffaella Viti, Andrea Marcellusi, Alessandro Capone & Francesco Saverio Mennini

  2. Institute for Leadership and Management in Health, Kingston University London, London, UK

    Andrea Marcellusi & Francesco Saverio Mennini

  3. Immunoallergology Unit, AOU Careggi, University of Florence, Florence, Italy

    Andrea Matucci & Alessandra Vultaggio

  4. Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy

    Claudio Pignata

  5. Department of Translational Medical Sciences, Center for Basic and Clinical Immunology Research, University of Naples Federico II, Naples, Italy

    Giuseppe Spadaro

  6. Department of Biomedical Sciences and Human Oncology, Section of Internal Medicine and Clinical Oncology, University of Bari Medical School, Bari, Italy

    Angelo Vacca & Carolina Marasco

  7. Department of Medicine (DIMED), Internal Medicine 1, Treviso Ca’ Foncello Hospital, University of Padua, Padua, Italy

    Carlo Agostini

Authors
  1. Raffaella Viti
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  2. Andrea Marcellusi
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  3. Alessandro Capone
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  4. Andrea Matucci
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  5. Alessandra Vultaggio
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  6. Claudio Pignata
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  7. Giuseppe Spadaro
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  8. Angelo Vacca
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  9. Carolina Marasco
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  10. Carlo Agostini
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  11. Francesco Saverio Mennini
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Corresponding author

Correspondence to Andrea Marcellusi.

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Funding

This analysis was funded by Baxalta SpA. The authors confirm that the paper is an accurate representation of the study results.

Conflicts of interest

Viti Raffaella, Marcellusi Andrea, Capone Alessandro, Matucci Andrea, Vultaggio Alessandra, Pignata Claudio, Spadaro Giuseppe, Vacca Angelo, Marasco Carolina, Agostini Carlo, and Mennini Francesco Saverio declare that there are no conflicts of interest regarding the publication of this paper.

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Viti, R., Marcellusi, A., Capone, A. et al. Direct and Indirect Costs of Immunoglobulin Replacement Therapy in Patients with Common Variable Immunodeficiency (CVID) and X-Linked Agammaglobulinemia (XLA) in Italy. Clin Drug Investig 38, 955–965 (2018). https://doi.org/10.1007/s40261-018-0688-3

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  • DOI: https://doi.org/10.1007/s40261-018-0688-3