Comparative pharmacoeconomic analysis of posaconazole therapy in tablet form and in suspension for invasive fungal infections prevention

The objective of the study was to conduct a comparative pharmacoeconomic analysis of the treatment with posaconazole in a tablet form for the prevention of invasive fungal infections in patients aged 13 years and older with prolonged neutropenia and hematopoietic stem cell transplant recipients.

Study design: pharmacoeconomic study, cost–effectiveness analysis; budget impact analysis; sensitivity analysis to changes in the initial parameters of the model.

Results and conclusion. A literature review has shown that the use of the compared drugs for the prevention of invasive fungal infections is effective, with posaconazole being the most effective. Based on pharmacokinetic studies data, we can state the equivalence of the action of various drug forms of posaconazole. A cost analysis of drugs showed that the lowest total costs were for the prevention of invasive fungal infections in patients with acute myeloid leukemia with posaconazole tablets (197,149.37 rub.) and posaconazole suspension (215,911.53 rub.). The lowest cost for the prevention of invasive fungal infections in patients with hematopoietic stem cell transplant was shown by posaconazole in tablets (505,070.37 rub.) and posaconazole in suspension (616,652.01 rub.). Budget impact analysis in acute myeloid leukemia patients showed that with a possible cohort size of 2288 people an increase in the share of posaconazole in tablets from 5 to 15 %, in suspension from 20 to 35 % and with a decrease in the share of voriconazole from 25 to 15 %, and the share of fluconazole from 50 to 35 % in public procurement will reduce budget costs by 30,441,219.72 rub., and in patients with hematopoietic stem cell transplant ‒ by 11,219,243.54 rub. (per 100 patients).

1. Vassilieva N.V., Klimko N.N., Zinserling V.A. Modern recommendations for diagnosis and treatment of invasive myсoses. Vestnik Sankt-Peterburgskoy medicinskoy akademii poslediplomnogo obrazovaniya = Bulletin of the Saint -Petersburg Medical Academy of Postgraduate Studies 2010;2(4):5–18. (In Russ.).

2. Malignant tumors in Russia in 2019 (morbidity and mortality). Eds.: А.D. Kaprin, V.V. Starinskiy, A.O. Shahzadova. Moscow: MNIOI im. P.A. Gertsena – filial FGBU “NMITS radiologii” Minzdrava Rossii, 2021. 252 p. (In Russ.).

3. Diagnosis and treatment of mycoses in intensive care units: Russian recommendations. Ed.: N.N. Klimko. 2nd edn. Moscow: Farmtek, 2015. 96 p. (In Russ.).

4. Walsh T.J., Anaissie E.J., Denning D.W. et al. Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America. Clin Infect Dis 2008;46(3):32–60. DOI: 10.1086/525258.

5. Dignani M.C. Epidemiology of invasive fungal diseases on the basis of autopsy reports. F1000Prime Rep 2014;6:81. DOI: 10.12703/P6-81.

6. Krueger K.P., Nelson A.C. Economic considerations in the treatment of invasive aspergillosis: a review of voriconazole pharmacoeconomic studies. Clinicoecon Outcomes Res 2009;1:35–43. DOI: 10.2147/ceor.s4244.

7. Nguyen S., Truong J.Q., Bruning J.B. Targeting unconventional pathways in pursuit of novel antifungals. Front Mol Biosci 2021;7:621366. DOI: 10.3389/fmolb.2020.621366.

8. Shen Y., Huang X.J., Wang J.X. et al. Posaconazole vs. fluconazole as invasive fungal infection prophylaxis in China: a multicenter, randomized, open-label study. Int J Clin Pharmacol Ther 2013;51(9):738–45. DOI: 10.5414/ CP201880.

9. Zhao Y.J., Khoo A.L., Tan G. et al. Network meta-analysis and pharmacoeconomic evaluation of fluconazole, itraconazole, posaconazole, and voriconazole in invasive fungal infection prophylaxis. Antimicrob Agents Chemother 2015;60(1):376–86. DOI: 10.1128/AAC.01985-15.

10. Lee C.H., Lin C., Ho C.L., Lin J.C. Primary fungal prophylaxis in hematological malignancy: a network meta-analysis of randomized controlled trials. Antimicrob Agents Chemother AAC.00355-18.

11. Su H.C., Hua Y.M., Feng I.J., Wu H.C. Comparative effectiveness of antifungal agents in patients with hematopoietic stem cell transplantation: a systematic review and network meta-analysis. Infect Drug Resist 2019;12:1311–24. DOI: 10.2147/IDR.S203579.

12. Wang J., Zhou M., Xu J. et al. Comparison of antifungal prophylaxis drugs in patients with hematological disease or undergoing hematopoietic stem cell transplantation: a systematic review and network metaanalysis. JAMA Netw Open 2020;3(10): e2017652. DOI: 10.1001/amanetworkopen.2020.17652.

13. Krysanov I.S., Klimko N.N., Ermakova V.Yu., Krysanova V.S. Comparative clinical and economic analysis of pozaconazol (Noxafil) for invasive mycoses (IM) prevention in patients with severe neutropenia during treatment of acute myeloid leukemia or myelodysplastic syndrome. Onkogematologiya = Oncohematology 2019;14(1):49–59. (In Russ.). DOI: 10.17650/1818-8346-2019-14-1-49-59.

14. The State register of limiting prices for vital medications 2020. Available at: http://www.grls.rosminzdrav.ru/Default.aspx. (In Russ.).

15. Vorob’ev P.A., Avksent’eva M.V., Borisenko O.V. et al. Clinical and economic analysis. Eds.: P.A. Vorob’ev. Moscow: N’yudiamed, 2004. 404 p. (In Russ.).

16. Omel’yanovskiy V.V., Avksenteva M.V., Sura M.V. et al. Guidelines for assessing the budget impact in the framework of the program of state guarantees of free medical care to citizens. Center of Expertise and Quality Control of Medical Care (CECCMC) of the Ministry of Health of Russia. Approved by the order of “CECCMC” of the Ministry of Health of Russia dated December 23, 2016 No. 145-од. Moscow, 2016. 28 p. (In Russ.).

17. Cornely O.A., Maertens J., Bresnik M. et al. Liposomal amphotericin B as initial therapy for invasive mold infection: a randomized trial comparing a highloading dose regimen with standard dosing (AmBiLoad trial). Clin Infect Dis 2007;44(10):1289–97. DOI: 10.1086/514341.

18. Benedict K., Jackson B.R., Chiller T., Beer K.D. Estimation of direct healthcare costs of fungal diseases in the United States. Clin Infect Dis 2019;68(11):1791–7. DOI: 10.1093/cid/ciy776.

19. Kim A., Nicolau D.P., Kuti J.L. Hospital costs and outcomes among intravenous antifungal therapies for patients with invasive aspergillosis in the United States. Mycoses 2011;54(5): e301–12. DOI: 10.1111/j.1439-0507.2010.01903.x.

20. Rieger C.T., Cornely O.A., Hoppe-Tichy T. et al. Treatment cost of invasive fungal disease (Ifd) in patients with acute myelogenous leukaemia (Aml) or myelodysplastic syndrome (Mds) in German hospitals. Mycoses 2012;55(6):514–20. DOI: 10.1111/j.1439-0507.2012.02193.x.

21. Rácil Z., Mayer J., Kocmanová I. et al. Invasive aspergillosis in hematooncological patients: advantages and disadvantages of various diagnostic methods, treatment options and financial costs of therapy. Vnitr Lek 2008;54(2):157–68.

22. Belousov Yu.B., Kolbin A.S., Koroleva O.A. et al. Clinical and economic expediency of posaconazole comparing with fluconazole and itraconazole in primary prophylaxis of systemic mycoses in severe neutropenic patients. Klinicheskaya mikrobiologiya i antimikrobnaya khimioterapiya = Clinical Microbiology and Antimicrobial Chemotherapy 2009;11(2):170–82. (In Russ.).

23. Cámara R., Gozalbo I., Jurado M. et al. Cost–effectiveness of posaconazole tablets for invasive fungal infections prevention in acute myelogenous leukemia or myelodysplastic syndrome patients in Spain. Adv Ther 2017;34(9):2104–19. DOI: 10.1007/s12325-017-0600-1.

24. Grau S., Cámara R., Jurado M. et al. Cost–effectiveness of posaconazole tablets versus fluconazole as prophylaxis for invasive fungal diseases in patients with graft-versushost disease after allogeneic hematopoietic stem cell transplantation. Eur J Health Econ 2018;19(4):627–36. DOI: 10.1007/s10198-017-0907-5.