harmacoeconomic feasibility of using the drug upadacitinib in patients with rheumatoid arthritis in the healthcare system of the Russian Federation

Aim. To assess the pharmacoeconomic feasibility of including the drug upadacitinib in restrictive lists and government funding programs to provide patients with rheumatoid arthritis.

Materials and methods. Study Design — Retrospective Analysisof Literary Data. Pharmacoeconomic analysis methods — indirect comparison, clinical-economic analysis (cost-effectiveness analysis) using sensitivity analysis; budget impact analysis using sensitivity analysis. Data on the effectiveness of the analyzed drugs are taken from publications on clinical studies of the compared drugs; on the cost of drugs — the state register of marginal selling prices, data of the manufacturer’s company.

Results. According to the results of indirect comparison, with respect to the frequency of achievement of the DAS28 test (CRP) <2.6, the effectiveness of the preparations tofacitinib and baricitinib does not significantly differ — OR = 1.275 (0.842; 1.931). At the same time, the preparation upadacitinib allows to achieve this indicator reliably more effective than the baricitinib — OR = 1.529 (1.021; 2.292) and tofacitinib — OR = 1.95 (1.285; 2.960). Costs for the use of upadacitinib against the background of methotrexate for 52 weeks will amount to 654 983.88 rubles, and will require 4.7 % less costs than the use of tofacitinib or baricitinib against the background of the use of methotrexate (687 217.53 rubles). In an indirect comparison of upadacitinib-baricitinib through the general comparator adalimumab, the effectiveness of upadacitinib with respect to the frequency of achievement of DAS28-CRP <2.6 turned out to be higher than baricitinib per 32.3 %. With indirect comparison of upadacitinib-tofacitinib under the same conditions, the efficiency of upadacitinib is 57.7 % higher than that of tofacitinib. Analysis of the impact on the budget showed that with the inclusion of the drug upadacitinib in the lists of VED and ONLS and a gradual increase in the proportion of patients, receiving upadacitinib instead of tofacitinib and baricitinib in the 1st year before 15 %, in the 2nd year — 30 %, in the 3rd year — 45 % for the group of 2.318 patients for 3 years, the reduction in the budget burden will be 1.4 % or 62.8 million rubles. With the provision of upadacitinib, 100 % of patients from the first year, the budget burden for 3 years will decrease by 4.7 % or 213.1 million rubles in comparison with the current regime.

Conclusion. tte drug upadacitinib at a lower course cost has greater effectiveness in achieving clinical remission according to the indicator DAS28-CRP (<2.6), and therefore its use in the conditions of the healthcare system of the Russian Federation for the treatment of patients with rheumatoid arthritis is pharmacoeconomic and expedient.

1. Nasonov EL, Karateev DE, Balabanova RM. Rheumatoid arthritis. In: Nasonov EL, Nasonova VA, editors. Revmatologiya. Natsional’noe rukovodstvo. Moscow: GEOTARMedia; 2008. 290—331 (In Russ).

2. Smolen JS, Aletaha D, McInnes IB. Rheumatoid arthritis. Lancet. 2016; 22;388(10055):2023—2038. DOI: 10.1016/S0140-6736(16)30173-8

3. Firestein GS. Kelley and Firesteins Textbook of Rheumatology. 10th ed. Philadelphia, Pennsylvania: Elsevier; Etiology and pathogenesis of rheumatoid arthritis. 2016;1115—66

4. Cutolo M, Kitas GD, van Riel PLCM. Burden of disease in treated rheumatoid arthritis patients: going beyond the joint. Semin Arthritis Rheum. 2014;43(4):479—488. DOI: 10.1016/j.semarthrit.2013.08.004

5. Klinicheskie rekomendacii. Revmatoidnyj artrit. 2018. (In Russ). Available from: http://cr.rosminzdrav.ru/#!/recomend/173/. Ссылка активна на 17.03.2020.

6. Proekt klinicheskih rekomendacij po lecheniyu revmatoidnogo artrita. 2020. (In Russ). Available from: https://rheumatolog.su/media/media/2019/12/11/proekt_kr_ra_1.pdf. Ссылка активна на 17.03.2020.

7. Smolen JS, Aletaha D, Bijlsma JWJ, et al. Treating rheumatoid arthritis to target: recommendations of an international task force. Ann Rheum Dis. 2010;69(4):631—637. DOI: 10.1136/ard.2009.123919

8. Smolen JS, Breedveld FC, Burmester GR, et al. Treating rheumatoid arthritis to target: 2014 update of the recommendations of an international task force. Ann Rheum Dis. 2016;75(1):3—15. DOI: 10.1136/annrheumdis-2015-20

9. Singh JA, Saag KG, Bridges SL Jr, et al. 2015 American College of Rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Rheum. 2016;68:1—26. DOI: 10.1002/art.22783

10. Daien CI, Hua C, Combe B, Landewe R. Non-pharmacological and pharmacological interventions in patients with early arthritis: a systematic literature review informing the 2016 update of EULAR recommendations for the management of early arthritis. RMD Open. 2017 Jan 5;3(1):e000404. DOI: 10.1136/rmdopen-2016-000404

11. Miossec P. Kinase inhibition in rheumatoid arthritis: a big advance? The Lancet. 2013;381, (9865):429—431. DOI: 10.1016/S0140-6736(12)61722-X

12. Giles J, Bathon JM. Management of rheumatoid arthritis: synovitis. Rheumatology. 2010;1:95563.

13. Fleischmann RM, Genovese MC, Enejosa JV, et al. Safety and effectiveness of upadacitinib or adalimumab plus methotrexate in patients with rheumatoid arthritis over 48 weeks with switch to alternate therapy in patients with insufficient response. Ann Rheum Dis. 2019 Nov;78(11):1454— 1462. DOI: 10.1136/annrheumdis-2019-215764

14. Instrukciya po medicinskomu primeneniyu lekarstvennogo sredstva RINVOQTM (upadacitinib). (In Russ). Available from: https://grls.rosminzdrav.ru/Grls_View_v2.aspx?routingGuid=46482d22-59ab-45de-bb33-1db07f96b110&t= Ссылка активна на 17.03.2020

15. Instrukciya po medicinskomu primeneniyu lekarstvennogo sredstva Olumiant (baricitinib). (In Russ). Available from: https://grls.rosminzdrav.ru/Grls_View_v2.aspx?routingGuid=6e78e3ed- 51b3-415a-a79c-3b06b503555f&t= Ссылка активна на 17.03.2020

16. Instrukciya po medicinskomu primeneniyu lekarstvennogo sredstva Jakvinus (tofacitinib). (In Russ). Available from: https://grls.rosminzdrav.ru/Grls_View_v2.aspx?routingGuid=de07b23b-ab5b-4899-92f4-f0636ec7c7bd&t= Ссылка активна на 17.03.2020

17. Instrukciya po medicinskomu primeneniyu lekarstvennogo sredstva Medak (methotrexate). (In Russ).] Available from: https://grls.rosminzdrav.ru/Grls_View_v2.aspx?routingGuid=26658a16-becd-4241-9146-9ac26d93aa08&t= Ссылка активна на 08.04.2020

18. Resolution of the Government of the Russian Federation of 28.08.2014 N 871 (ed. from 20.11.2018). “Ob utverzhdenii Pravil formirovaniya perechnej lekarstvennyh preparatov dlya medicinskogo primeneniya i minimal’nogo assortimenta lekarstvennyh preparatov, neobhodimyh dlya okazaniya medicinskoj pomoshchi” (In Russ).]19. Jagpal A, Navarro-Millan I. Cardiovascular co-morbidity in patients with rheumatoid arthritis: a narrative review of risk factors, cardiovascular risk assessment and treatment. BMC Rheumatol. 2018;2:10. DOI: 10.1186/s41927-018-0014-y

19. Solomon DH, Reed G, Kremer JM, et al. Disease Activity in Rheumatoid Arthritis and the Risk of Cardiovascular Events. Arthritis Rheumatol. 2015;67(6):1449—1455. DOI:10.1002/art.39098

20. Linde L, Sorensen J, Ostergaard M, et al. Does clinical remission lead to normalization of EQ-5D in patients with rheumatoid arthritis and is selection of remission criteria important? J Rheumatol. 2010;37(2):285—290. DOI:10.3899/jrheum.090898

21. Mjaavatten MD, Radner H, Yoshida K, et al. Inconsistent treatment with disease-modifying antirheumatic drugs: a longitudinal data analysis. J Rheumatol. 2014;41(12):2370—2378. DOI:10.3899/jrheum.140306

22. Codreanu C, Popescu CC, Mogo^an C. Area of Residence and Socioeconomic Factors Reduce Access to Biologics for Rheumatoid Arthritis Patients in Romania. Biomed Res Int. 2018;7458361. Published 2018 May 8. DOI:10.1155/2018/7458361

23. Nikiphorou E, Norton S, Young A, et al. Association between rheumatoid arthritis disease activity, progression of functional limitation and long-term risk of orthopaedic surgery: combined analysis of two prospective cohorts supports EULAR treat to target DAS thresholds. Ann Rheum Dis. 2016;75(12):2080—2086. DOI:10.1136/annrheumdis-2015-208669

24. Fleischmann R, Mysler E, Hall S, et al. Efficacy and safety of tofacitinib monotherapy, tofacitinib with methotrexate, and adalimumab with methotrexate in patients with rheumatoid arthritis (ORAL Strategy): a phase 3b/4, double-blind, head-to-head, randomised controlled trial. Lancet. 2017 Jul 29;390(10093):457—468. DOI: 10.1016/S0140-6736(17)31618-5

25. Taylor PC, Keystone EC, van der Heijde D., et al. Baricitinib versus Placebo or Adalimumab in Rheumatoid Arthritis. N Engl J Med. 2017 Feb 16;376(7):652—662. DOI: 10.1056/NEJMoa1608345

26. Metodicheskie rekomendacii po provedeniyu nepryamyh sravnenij lekarstvennyh preparatov. FGBU «CEKKMP» Minzdrava Rossii, 2017. (In Russ).

27. informacionnaya sistema v sfere zakupok. (In Russ). Available from: https://zakupki.gov.ru/epz/main/public/home.html Ссылка активна на 17.03.2020

28. Edinaya informacionnaya sistema v sfere zakupok. (In Russ). Available from: https://zakupki.gov.ru/epz/main/public/home.html