Skip to main content

Pharmacoeconomic evaluation of tiotropium bromide in the long-term treatment of chronic obstructive pulmonary disease (COPD) in Italy

A Commentary to this article was published on 10 May 2012

Abstract

The randomized, double-blind trial UPLIFT® demonstrated in 5,993 patients with moderate to very severe COPD that 4 years of tiotropium bromide therapy were associated with improvements in lung function, exacerbations, quality of life, and mortality compared with placebo. The pharmacoeconomic evaluation was performed through a probabilistic, patient-level simulation Markov model. Routine COPD care (RC) was compared with the inclusion of tiotropium bromide on it. The analysis was conducted over a lifetime horizon, with 1 year cycles and a 3.5% annual discount rate. Patients were characterized by gender, age, height, smoking status, and forced expiratory volume in 1 s (FEV1). FEV1 time trend was modeled according to the annual decline recorded in UPLIFT®. Mortality derived from that of the general Italian population was adjusted by smoking status and FEV1. Health utilities derived from published Italian observational studies and were varied in time according to UPLIFT® data. Exacerbation rates were derived from a published Italian observational prospective study. The cost perspective was that of the Italian National Health Service. Healthcare resource consumption for RC and exacerbations derived from Italian observational studies were valued according to current price and tariffs. Simulated patients in the tiotropium arm gained an average (95% CI) 0.50 (−1.63 to 6.27) Life Years (LYs) and 0.42 (−0.25 to 3.05) Quality-Adjusted Life Years (QALYs). The incremental lifetime cost resulted €3,357 (−€10,669 to €29,820). The incremental cost-effectiveness ratio (ICER) was €6,698/LY and €7,916/QALY. In the cost-effectiveness acceptability curve (CEAC), tiotropium had a 90% probability of being cost-effective for a willingness to pay (WTP) threshold of € 10,000/QALY.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3

References

  1. WHO—World Health Organization: World health report. WHO, Geneva (2000)

    Google Scholar 

  2. Stang, P., Lydick, E., Silberman, C., Kempel, A., Keating, E.T.: The prevalence of COPD: using smoking rates to estimate disease frequency in the general population. Chest 117, 354S–359S (2000)

    PubMed  Article  CAS  Google Scholar 

  3. Feenstra, T.L., van Genugten, M.L., Hoogenveen, R.T., Wouters, E.F., Rutten-van Mölken, M.P.: The impact of aging and smoking on the future burden of chronic obstructive pulmonary disease: a model analysis in the Netherlands. Am. J. Respir. Crit. Care Med. 164, 590–596 (2001)

    PubMed  CAS  Google Scholar 

  4. Oostenbrink, J.B., Rutten-van Mölken, M.P.M.H.: Resource use and risk factors in high-cost exacerbations of COPD. Respir. Med. 98, 883–891 (2004)

    PubMed  Article  Google Scholar 

  5. Miravitlles, M., Murio, C., Guerrero, T., Gisbert, R.: Costs of chronic bronchitis and COPD: a 1-year follow-up study. Chest 123, 784–791 (2003)

    PubMed  Article  Google Scholar 

  6. Andersson, F., Borg, S., Jansson, S.A., Jonsson, A.C., Ericsson, A., Prütz, C., Rönmark, E., Lundbäck, B.: The costs of exacerbations in chronic obstructive pulmonary disease (COPD). Respir. Med. 96, 700–708 (2002)

    PubMed  Article  CAS  Google Scholar 

  7. Dal Negro, R., Rossi, A., Cerveri, I.: The burden of COPD in Italy: results from the Confronting COPD survey. Respir. Med. 97(Suppl C), S43–S50 (2003)

    PubMed  Article  Google Scholar 

  8. Koleva, D., Motterlini, N., Banfi, P., Garattini, L.: Healthcare costs of COPD in Italian referral centres: a prospective study. Respir. Med. 101, 2312–2320 (2007)

    PubMed  Article  Google Scholar 

  9. Lucioni, C., Donner, C., De Benedetto, F., Lusuardi, M., Mazzi, S., Paggiaro, P., Sanguinetti, C.: I costi della broncopneumopatia cronica ostruttiva: la fase prospettica dello Studio ICE (Italian Costs for Exacerbations in COPD). PharmacoEconomics—Italian Research Articles 7, 119–134 (2005)

    Google Scholar 

  10. Casaburi, R., Mahler, D.A., Jones, P.W., Wanner, A., San, P.G., ZuWallack, R.L., Menjoge, S.S., Serby, C.W., Witek, T.J.: A long-term evaluation of once-daily inhaled tiotropium bromide in chronic obstructive pulmonary disease. Eur. Respir. J. 19, 217–224 (2002)

    PubMed  Article  CAS  Google Scholar 

  11. Vincken, W., van Noord, J.A., Greefhorst, A.P.M., Bantje, T.A., Kesten, S., Korducki, L., Cornelissen, P.J.G.: Improved health outcomes in patients with COPD during 1 yr’s treatment with tiotropium bromide. Eur. Respir. J. 19, 209–216 (2002)

    PubMed  Article  CAS  Google Scholar 

  12. Brusasco, V., Hodder, R., Miravitlles, M., Korducki, L., Towse, L., Kesten, S.: Health outcomes following treatment for six months with once daily tiotropium bromide compared with twice daily salmeterol in patients with COPD. Thorax 58, 399–404 (2003)

    PubMed  Article  CAS  Google Scholar 

  13. Tashkin, D.P., Celli, B., Senn, S., Burkhart, D., Kesten, S., Menjoge, S., Decramer, M.: A 4-year trial of tiotropium bromide in chronic obstructive pulmonary disease. N. Engl. J. Med. 359, 1543–1554 (2008)

    PubMed  Article  CAS  Google Scholar 

  14. Dal Negro, R.W., Tognella, S., Tosatto, R., Dionisi, M., Turco, P., Donner, C.F.: Costs of chronic obstructive pulmonary disease (COPD) in Italy: the SIRIO study (social impact of respiratory integrated outcomes). Respir. Med. 102, 92–101 (2008)

    PubMed  Article  CAS  Google Scholar 

  15. Antonelli-Incalzi, R., Imperiale, C., Bellia, V., Catalano, F., Scichilone, N., Pistelli, R., Rengo, F.: Do GOLD stages of COPD severity really correspond to differences in health status? Eur. Respir. J. 22, 444–449 (2003)

    PubMed  Article  CAS  Google Scholar 

  16. Aaron, S.D., Vandemheen, K.L., Fergusson, D., Maltais, F., Bourbeau, J., Goldstein, R., Balter, M., O’Donnell, D., McIvor, A., Sharma, S., Bishop, G., Anthony, J., Cowie, R., Field, S., Hirsch, A., Hernandez, P., Rivington, R., Road, J., Hoffstein, V., Hodder, R., Marciniuk, D., McCormack, D., Fox, G., Cox, G., Prins, H.B., Ford, G., Bleskie, D., Doucette, S., Mayers, I., Chapman, K., Zamel, N., FitzGerald, M.: Tiotropium bromide in combination with placebo, salmeterol, or fluticasone-salmeterol for treatment of chronic obstructive pulmonary disease: a randomized trial. Ann. Intern. Med. 146, 545–555 (2007)

    PubMed  Google Scholar 

  17. Borrill, Z.L., Houghton, C.M., Tal-Singer, R., Vessey, S.R., Faiferman, I., Langley, S.J., Singh, D.: The use of plethysmography and oscillometry to compare long-acting bronchodilators in patients with COPD. Br. J. Clin. Pharmacol. 65, 244–252 (2008)

    PubMed  Article  CAS  Google Scholar 

  18. Freeman, D., Lee, A., Price, D.: Efficacy and safety of tiotropium bromide in COPD patients in primary care—the SPiRiva Usual CarE (SPRUCE) study. Respir Res 8, 45 (2007)

    PubMed  Article  Google Scholar 

  19. Verkindre, C., Bart, F., Aguilaniu, B., Fortin, F., Guérin, J., Le Merre, C., Iacono, P., Huchon, G.: The effect of tiotropium bromide on hyperinflation and exercise capacity in chronic obstructive pulmonary disease. Respiration 73, 420–427 (2006)

    PubMed  Article  CAS  Google Scholar 

  20. Maltais, F., Hamilton, A., Marciniuk, D., Hernandez, P., Sciurba, F.C., Richter, K., Kesten, S., O’Donnell, D.: Improvements in symptom-limited exercise performance over 8 h with once-daily tiotropium bromide in patients with COPD. Chest 128, 1168–1178 (2005)

    PubMed  Article  CAS  Google Scholar 

  21. Niewoehner, D.E., Rice, K., Cote, C., Paulson, D., Cooper, J.A.D.J., Korducki, L., Cassino, C., Kesten, S.: Prevention of exacerbations of chronic obstructive pulmonary disease with tiotropium bromide, a once-daily inhaled anticholinergic bronchodilator: a randomized trial. Ann. Intern. Med. 143, 317–326 (2005)

    PubMed  CAS  Google Scholar 

  22. O’Donnell, D.E., Flüge, T., Gerken, F., Hamilton, A., Webb, K., Aguilaniu, B., Make, B., Magnussen, H.: Effects of tiotropium bromide on lung hyperinflation, dyspnoea and exercise tolerance in COPD. Eur. Respir. J. 23, 832–840 (2004)

    PubMed  Article  Google Scholar 

  23. van Noord, J.A., Aumann, J.L., Janssens, E., Verhaert, J., Smeets, J.J., Mueller, A., Cornelissen, P.J.G.: Effects of tiotropium bromide with and without formoterol on airflow obstruction and resting hyperinflation in patients with COPD. Chest 129, 509–517 (2006)

    PubMed  Article  Google Scholar 

  24. ISTAT—National Institute of Statistics. Mortality tables of the general population 2006. Available online at http://demo.istat.it/unitav/index.html?lingua=ita. Last accessed Apr 2009

  25. WHO/Europe: European health for all database (HFA-DB). Available on line at http://data.euro.who.int/hfadb/tables/tableC.php?w=1280&h=1024. Last accessed Apr 2008

  26. Lange, P., Nyboe, J., Appleyard, M., Jensen, G., Schnohr, P.: Relation of ventilatory impairment and of chronic mucus hypersecretion to mortality from obstructive lung disease and from all causes. Thorax 45, 579–585 (1990)

    PubMed  Article  CAS  Google Scholar 

  27. Ståhl, E., Lindberg, A., Jansson, S., Rönmark, E., Svensson, K., Andersson, F., Löfdahl, C., Lundbäck, B.: Health-related quality of life is related to COPD disease severity. Health Qual Life Outcomes 3, 56 (2005)

    PubMed  Article  Google Scholar 

  28. Ferrario, M.M., Fornari, C., Bolognesi, L., Gussoni, M.T., Benedetti, M., Sega, R., Borchini, R., Cesana, G.: Recent time trends of myocardial infarction rates in northern Italy. Results from the MONICA and CAMUNI registries in Brianza: 1993–1994 versus 1997–1998. Ital. Heart J. Suppl. 4, 651–657 (2003)

    Google Scholar 

  29. ANMCO Consensus Conference.: Il percorso assistenziale del paziente con scompenso cardiaco. G. Ital. Cardiol. Giugno 7 (2006)

  30. Sidney, S., Sorel, M., Quesenberry, C.P.J., DeLuise, C., Lanes, S., Eisner, M.D.: COPD and incident cardiovascular disease hospitalizations and mortality: Kaiser permanente medical care program. Chest 128, 2068–2075 (2005)

    PubMed  Article  Google Scholar 

  31. Italian Specialist Tariffs. Nomenclatore Tariffario Nazionale D.M. 22 luglio 1996

  32. Nomenclatore Tariffario Nazionale: DRG Tariffs. DMS 12/09/2006. Supplemento Ordinario alla Gazzetta Ufficiale n. 289 del 13/12/2006

  33. HDR—Hospital Discharge Records database. Available online at http://www.ministerosalute.it/programmazione/sdo/ric_informazioni/default.jsp. Last accessed Apr 2009

  34. Italian Drug Formulary: Informatore Farmaceutico, 69a edizione. Elsevier Masson (2009)

  35. World Health Organization: WHO/CHOosing interventions that are cost/effective (WHO-CHOICE), 2000. Available online at http://www.who.int/choice. Last accessed Dec 2008

  36. Laupacis, A., Feeny, D., Detsky, A.S., Tugwell, P.X.: How attractive does a new technology have to be to warrant adoption and utilization? Tentative guidelines for using clinical and economic evaluations. CMAJ 146, 473–481 (1992)

    PubMed  CAS  Google Scholar 

  37. Tosteson, A.N.: Quality of life in the economic evaluation of osteoporosis prevention and treatment. Spine (Phila Pa 1976) 22:58S–62S (1997)

    Google Scholar 

  38. Kanis, J.A., Jonsson, B.: Economic evaluation of interventions for osteoporosis. Osteoporos. Int. 13, 765–767 (2002)

    PubMed  Article  CAS  Google Scholar 

  39. Raftery, J.: NICE: faster access to modern treatments? Analysis of guidance on health technologies. Br Med J 323, 1300–1303 (2001)

    Article  CAS  Google Scholar 

  40. ISTAT—National Institute of Statistics: Historical series of per capita gross domestic product (GDP) (1970–2007). Available online at http://www.istat.it/conti/. Last accessed Feb 2009

  41. Oostenbrink, J.B., Rutten-van Mölken, M.P.M.H., Monz, B.U., FitzGerald, J.M.: Probabilistic Markov model to assess the cost-effectiveness of bronchodilator therapy in COPD patients in different countries. Value Health 8, 32–46 (2005)

    PubMed  Article  Google Scholar 

  42. Rutten-van Mölken, M.P.M.H., Oostenbrink, J.B., Miravitlles, M., Monz, B.U.: Modelling the 5-year cost effectiveness of tiotropium bromide, salmeterol and ipratropium for the treatment of chronic obstructive pulmonary disease in Spain. Eur J Health Econ 8, 123–135 (2007)

    PubMed  Article  Google Scholar 

  43. Maniadakis, N., Tzanakis, N., Fragoulakis, V., Hatzikou, M., Siafakas, N.: Economic evaluation of tiotropium bromide and salmeterol in the treatment of chronic obstructive pulmonary disease (COPD) in Greece. Curr. Med. Res. Opin. 22, 1599–1607 (2006)

    PubMed  Article  Google Scholar 

  44. Nishimura S, Kobayashi M, Hasegawa T.: Cost-effectiveness analysis of tiotropium bromide for chronic obstructive pulmonary disease (COPD) patients in Japan. ISPOR 10th Annual International Meeting, 2005. Washington, DC, USA

  45. Brosa, M., Díaz, S., Miravitlles, M., Gonzalez-Rojas, N., Nieves, D.: Cost-effectiveness analysis of tiotropium bromide in the treatment of chronic obstructive pulmonary disease (COPD) patients in Spain. ISPOR 12th Annual European Congress, 2009. Paris, France

  46. De Lucas, P., Rodríguez, J., Gobartt, E., Soto, J., Martin, A.: Pharmacoeconomic evaluation of tiotropium bromide in the treatment of patients with chronic obstructive pulmonary disease in Spain. ISPOR 8th European Congress, 2005. Florence, Italy

  47. Onukwugha, E., Mullins, C.D., DeLisle, S.: Using cost-effectiveness analysis to sharpen formulary decision-making: the example of tiotropium bromide at the veterans affairs health care system. Value Health 11, 980–988 (2008)

    PubMed  Article  Google Scholar 

  48. Schramm, W., Haake, D., Brandt, A.: Economic value of tiotropium bromide in the treatment of chronic obstructive pulmonary disease. Praxis (Bern 1994) 94:1803–1810 (2005)

    Google Scholar 

  49. Lee, K., Phua, J., Lim, T.: Evaluating the pharmacoeconomic effect of adding tiotropium bromide to the management of chronic obstructive pulmonary disease patients in Singapore. Respir. Med. 100, 2190–2196 (2006)

    PubMed  Article  Google Scholar 

  50. Oba, Y.: Cost-effectiveness of salmeterol, fluticasone, and combination therapy for COPD. Am J Manag Care 15, 226–232 (2009)

    PubMed  Google Scholar 

  51. Earnshaw, S.R., Wilson, M.R., Dalal, A.A., Chambers, M.G., Jhingran, P., Stanford, R., Mapel, D.W.: Cost-effectiveness of fluticasone propionate/salmeterol (500/50 microg) in the treatment of COPD. Respir. Med. 103, 12–21 (2009)

    PubMed  Article  Google Scholar 

  52. Spencer, M., Briggs, A.H., Grossman, R.F., Rance, L.: Development of an economic model to assess the cost effectiveness of treatment interventions for chronic obstructive pulmonary disease. Pharmacoeconomics 23, 619–637 (2005)

    PubMed  Article  CAS  Google Scholar 

  53. Miravitlles, M., Murio, C., Guerrero, T., Gisbert, R.: Pharmacoeconomic evaluation of acute exacerbations of chronic bronchitis and COPD. Chest 121, 1449–1455 (2002)

    PubMed  Article  Google Scholar 

  54. Ram, F.S.F., Wedzicha, J.A., Wright, J., Greenstone, M.: Hospital at home for patients with acute exacerbations of chronic obstructive pulmonary disease: systematic review of evidence. BMJ 329, 315 (2004)

    PubMed  Article  Google Scholar 

  55. Jahnz-Rozyk, K.M., Targowski, T., From, S.: Costs of COPD exacerbations in Poland (results of the pilot study). ISPOR 9th Annual European Congress. Copenhagen, Denmark

  56. Spannheimer, A., Schlegel, C., Reitberger, U., Welsch, R., Ruckdaeschel, S.: Costs of COPD in Germany—results of a cost-of illness study. ISPOR 6th Annual European Congress. Barcelona, Spain

  57. Halpin, D.M.G., Miravitlles, M.: Chronic obstructive pulmonary disease. The Disease and Its Burden to Society. Proc Am Thorac Soc 3, 619–623 (2006)

    PubMed  Article  Google Scholar 

  58. Seemungal, T.A.R., Hurst, J.R., Wedzicha, J.A.: Exacerbation rate, health status and mortality in COPD–a review of potential interventions. Int J Chron Obstruct Pulmon Dis 4, 203–223 (2009)

    PubMed  Google Scholar 

  59. FitzGerald, J.M., Haddon, J.M., Bradly-Kennedy, C., Kuramoto, L., Ford, G.T.: Resource use study in COPD (RUSIC): a prospective study to quantify the effects of COPD exacerbations on health care resource use among COPD patients. Can Respir J 14, 145–152 (2007)

    PubMed  Google Scholar 

  60. Mantovani, L.G., Mannino, S., Donner, C.E., et al.: The cost of COPD: Results from the SIRIBO (Studio Italiano sulle Riacutizzazioni Infettive delle Bronchiti). Eur. Respir. J. 20(suppl 38) (2002)

  61. Ferrara Statistical Service. Available on line at http://servizi.comune.fe.it/attach/statistica/docs/informanumeri7_04abitudine_al_fumo_e_obesita.pdf (2003). Last accessed Apr 2009

Download references

Acknowledgments

O. Zaniolo, L. Pradelli and S. Iannazzo are employees of AdRes Srl, Torino, Italy, an independent health economics consulting and research company. Boehringer Ingelheim Italia S.p.A., Milan, Italy supported the development of the model through a service contract with AdRes. M Miravitlles has received honoraria for lecturing and participating in advisory board for Boehringer Ingelheim G.m.b.H.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to S. Iannazzo.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Zaniolo, O., Iannazzo, S., Pradelli, L. et al. Pharmacoeconomic evaluation of tiotropium bromide in the long-term treatment of chronic obstructive pulmonary disease (COPD) in Italy. Eur J Health Econ 13, 71–80 (2012). https://doi.org/10.1007/s10198-010-0285-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10198-010-0285-8

Keywords

  • COPD
  • Economic evaluation
  • Italy
  • UPLIFT
  • Tiotropium

JEL Classification

  • I19