Cost-Effectiveness of Tofacitinib for Patients with Moderate-to-Severe Rheumatoid Arthritis in China

Abstract

Background

Patients with moderate-to-severe rheumatoid arthritis have a heavy financial burden. The cost-effectiveness of introducing tofacitinib to the current treatment sequence for patients with moderate-to-severe rheumatoid arthritis who have inadequate response or intolerance to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs-IR) in China remains unknown.

Objective

The objective of this study was to assess the cost-effectiveness of introducing tofacitinib into the current treatment sequence in China for patients with moderate-to-severe rheumatoid arthritis who have csDMARDs-IR.

Methods

A Markov model was constructed from the perspective of the Chinese healthcare system to compare treatment sequences with and without first-line tofacitinib for patients with rheumatoid arthritis with csDMARDs-IR. The treatment sequence without tofacitinib included adalimumab, etanercept, recombinant human tumor necrosis factor receptor-Fc fusion protein, infliximab, and tocilizumab. Costs were derived from publicly available sources. Clinical trials, network meta-analysis, and real-world data were used to generate quality-adjusted life-years (QALYs), transition probabilities, and the incidence of adverse events. Mortality probabilities were estimated from rheumatoid arthritis-based, Chinese all-cause mortality data. One-way and probabilistic sensitivity analyses were conducted to verify the robustness of the model. In addition, the cost-effectiveness of adding tofacitinib as second- and third-line treatment options was evaluated in our analyses. Costs and effects were discounted at 5% per anum.

Results

Compared to the current treatment sequence, adding tofacitinib as first-line treatment led to a cost-saving of $US880.11 (2018 values) and incremental QALYs of 1.34. Sensitivity analyses showed the results to be robust. Adding tofacitinib at second-line therapy was also a cost-saving option with a cost saving of $US653.65 and incremental QALYs of 1.34, while the incremental cost-effectiveness ratio of adding tofacitinib at third-line therapy was $US5588.14 per QALY gained.

Conclusions

Using the WHO-recommended ICER acceptability threshold of ≤ 1-time per capita Gross Domestic Product (GDP), our analysis suggests that the introduction of tofacitinib into the current treatment sequence for moderate-to-severe RA patients with csDMARDs-IR in China was a cost saving option as first- and second-line treatment, and cost-effective as a third-line treatment option. Of note, use of tofacitinib as first- and second-line treatment post-csDMARDs-IR appeared to be cost saving.

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References

  1. 1.

    Aletaha D, Neogi T, Silman AJ, et al. Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum. 2010;62(9):2569–81.

    PubMed  PubMed Central  Google Scholar 

  2. 2.

    Firestein GS. Evolving concepts of rheumatoid arthritis. Nature. 2003;423(6937):356–61.

    CAS  PubMed  Google Scholar 

  3. 3.

    Harris ED Jr. Rheumatoid arthritis: pathophysiology and implications for therapy. N Engl J Med. 1990;322(18):1277–89.

    PubMed  Google Scholar 

  4. 4.

    Mcinnes IB, Schett G. The pathogenesis of rheumatoid arthritis. N Engl J Med. 2011;365(23):2205–19.

    CAS  PubMed  Google Scholar 

  5. 5.

    Chinese Rheumatology Association. 2018 Chinese guideline for the diagnosis and treatment of rheumatoid arthritis. Chin J Intern Med. 2018;4:242–51.

    Google Scholar 

  6. 6.

    Xu C, Wang X, Mu R, et al. Societal costs of rheumatoid arthritis in China: a hospital-based cross-sectional study. Arthritis Care Res (Hoboken). 2014;66(4):523–31.

    Google Scholar 

  7. 7.

    Smolen JS, Steiner G. Therapeutic strategies for rheumatoid arthritis. Nat Rev Drug Discov. 2003;2(6):473–88.

    CAS  PubMed  Google Scholar 

  8. 8.

    Sandborn WJ, Ghosh S, Panes J, et al. Tofacitinib, an oral Janus kinase inhibitor, in active ulcerative colitis. N Engl J Med. 2012;367(7):616–24.

    CAS  PubMed  Google Scholar 

  9. 9.

    Pfizer. Pfizer announces approval by the China Food and Drug Administration of Xeljanz®, the first oral JAK inhibitor for adult patients with moderately to severely active rheumatoid arthritis. https://www.pfizer.com/news/press-release/press-release-detail/pfizer_announces_approval_by_the_china_food_and_drug_administration_of_xeljanz_the_first_oral_jak_inhibitor_for_adult_patients_with_moderately_to_severely_active_rheumatoid_arthritis. Accessed 15 July 2019.

  10. 10.

    Fleischmann R, Kremer J, Cush J, et al. Placebo-controlled trial of tofacitinib monotherapy in rheumatoid arthritis. N Engl J Med. 2012;367(6):495–507.

    CAS  PubMed  Google Scholar 

  11. 11.

    van der Heijde D, Tanaka Y, Fleischmann R, et al. Tofacitinib (CP-690,550) in patients with rheumatoid arthritis receiving methotrexate: twelve-month data from a twenty-four-month phase III randomized radiographic study. Arthritis Rheum. 2013;65(3):559–70.

    PubMed  Google Scholar 

  12. 12.

    Strand V, Kremer J, Wallenstein G, et al. Effects of tofacitinib monotherapy on patient-reported outcomes in a randomized phase 3 study of patients with active rheumatoid arthritis and inadequate responses to DMARDs. Arthritis Res Ther. 2015;17:307.

    PubMed  PubMed Central  Google Scholar 

  13. 13.

    Kremer J, Li ZG, Hall S, et al. Tofacitinib in combination with nonbiologic disease-modifying antirheumatic drugs in patients with active rheumatoid arthritis: a randomized trial. Ann Intern Med. 2013;159(4):253–61.

    PubMed  Google Scholar 

  14. 14.

    van Vollenhoven RF, Fleischmann R, Cohen S, et al. Tofacitinib or adalimumab versus placebo in rheumatoid arthritis. N Engl J Med. 2012;367(6):508–19.

    PubMed  Google Scholar 

  15. 15.

    Burmester GR, Blanco R, Charles-Schoeman C, et al. Tofacitinib (CP-690,550) in combination with methotrexate in patients with active rheumatoid arthritis with an inadequate response to tumour necrosis factor inhibitors: a randomised phase 3 trial. Lancet. 2013;381(9865):451–60.

    CAS  PubMed  Google Scholar 

  16. 16.

    Lee MY, Park SK, Park SY, et al. Cost-effectiveness of tofacitinib in the treatment of moderate to severe rheumatoid arthritis in South Korea. Clin Ther. 2015;37(8):1662–76.e2.

    PubMed  Google Scholar 

  17. 17.

    Carlson JJ, Ogale S, Dejonckheere F, et al. Economic evaluation of tocilizumab monotherapy compared to adalimumab monotherapy in the treatment of severe active rheumatoid arthritis. Value Health. 2015;18(2):173–9.

    PubMed  Google Scholar 

  18. 18.

    Weaver AL. The impact of new biologicals in the treatment of rheumatoid arthritis. Rheumatology (Oxford). 2004;43(Suppl 3):iii17–iii23.

    Google Scholar 

  19. 19.

    Li ZG, Liu Y, Xu HJ, et al. Efficacy and safety of tofacitinib in Chinese patients with rheumatoid arthritis. Chin Med J (Engl). 2018;131(22):2683–92.

    Google Scholar 

  20. 20.

    Li Z, An Y, Su H, et al. Tofacitinib with conventional synthetic disease-modifying antirheumatic drugs in Chinese patients with rheumatoid arthritis: patient-reported outcomes from a phase 3 randomized controlled trial. Int J Rheum Dis. 2018;21(2):402–14.

    CAS  PubMed  PubMed Central  Google Scholar 

  21. 21.

    Bergrath E, Gerber RA, Gruben D, et al. Tofacitinib versus biologic treatments in moderate-to-severe rheumatoid arthritis patients who have had an inadequate response to nonbiologic DMARDs: systematic literature review and network meta-analysis. Int J Rheumatol. 2017;2017:8417249.

    PubMed  PubMed Central  Google Scholar 

  22. 22.

    Klareskog L, Gaubitz M, Rodriguez-Valverde V, et al. A long-term, open-label trial of the safety and efficacy of etanercept (Enbrel) in patients with rheumatoid arthritis not treated with other disease-modifying antirheumatic drugs. Ann Rheum Dis. 2006;65(12):1578–84.

    CAS  PubMed  PubMed Central  Google Scholar 

  23. 23.

    ClinicalTrials.gov. Abatacept and infliximab in combination with methotrexate in subjects with rheumatoid arthritis: study results. https://www.clinicaltrials.gov/ct2/show/results/NCT00095147?term=NCT00095147&rank=1&view=results#outcome45. Accessed 15 July 2019.

  24. 24.

    Schiff M, Keiserman M, Codding C, et al. Efficacy and safety of abatacept or infliximab vs placebo in ATTEST: a phase III, multi-centre, randomised, double-blind, placebo-controlled study in patients with rheumatoid arthritis and an inadequate response to methotrexate. Ann Rheum Dis. 2008;67(8):1096–103.

    CAS  PubMed  Google Scholar 

  25. 25.

    Burmester GR, Rubbert-Roth A, Cantagrel A, et al. Efficacy and safety of subcutaneous tocilizumab versus intravenous tocilizumab in combination with traditional DMARDs in patients with RA at week 97 (SUMMACTA). Ann Rheum Dis. 2016;75(1):68–74.

    CAS  PubMed  Google Scholar 

  26. 26.

    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;390(10093):457–68.

    CAS  PubMed  Google Scholar 

  27. 27.

    Koike T, Harigai M, Inokuma S, et al. Effectiveness and safety of tocilizumab: postmarketing surveillance of 7901 patients with rheumatoid arthritis in Japan. J Rheumatol. 2014;41(1):15–23.

    CAS  PubMed  Google Scholar 

  28. 28.

    Curtis JR, Xie F, Yun H, et al. Real-world comparative risks of herpes virus infections in tofacitinib and biologic-treated patients with rheumatoid arthritis. Ann Rheum Dis. 2016;75(10):1843–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  29. 29.

    Koike T, Harigai M, Inokuma S, et al. Postmarketing surveillance of the safety and effectiveness of etanercept in Japan. J Rheumatol. 2009;36(5):898–906.

    CAS  PubMed  Google Scholar 

  30. 30.

    Takeuchi T, Tatsuki Y, Nogami Y, et al. Postmarketing surveillance of the safety profile of infliximab in 5000 Japanese patients with rheumatoid arthritis. Ann Rheum Dis. 2008;67(2):189–94.

    CAS  PubMed  Google Scholar 

  31. 31.

    Tanaka Y, Mimori T, Yamanaka H, et al. Safety and effectiveness of adalimumab in Japanese rheumatoid arthritis patients: postmarketing surveillance report of 7740 patients. Mod Rheumatol. 2019;29(4):572–80.

    CAS  PubMed  Google Scholar 

  32. 32.

    Claxton L, Taylor M, Gerber RA, et al. Modelling the cost-effectiveness of tofacitinib for the treatment of rheumatoid arthritis in the United States. Curr Med Res Opin. 2018;34(11):1991–2000.

    CAS  PubMed  Google Scholar 

  33. 33.

    Hassett B, Scheinberg M, Castaneda-Hernandez G, et al. Variability of intended copies for etanercept (Enbrel®): data on multiple batches of seven products. MAbs. 2018;10(1):166–76.

    CAS  PubMed  Google Scholar 

  34. 34.

    Castañeda-Hernández G, González-Ramírez R, Kay J, Scheinberg MA. Biosimilars in rheumatology: what the clinician should know. RMD Open. 2015;1(1):e000010.

    PubMed  PubMed Central  Google Scholar 

  35. 35.

    Barton P, Jobanputra P, Wilson J, et al. The use of modelling to evaluate new drugs for patients with a chronic condition: the case of antibodies against tumour necrosis factor in rheumatoid arthritis. Health Technol Assess. 2004;8(11):iii1–iii91.

    Google Scholar 

  36. 36.

    Department of Population and Employment Statistics of the National Bureau of Statistics of China. China population and employment statistics yearbook 2017. Beijing: China Statistics Press; 2018.

    Google Scholar 

  37. 37.

    National healthcare security administration. https://www.nhsa.gov.cn/art/2019/11/28/art_37_2050.html. Accessed 26 Jan 2020.

  38. 38.

    National healthcare security administration. https://www.nhsa.gov.cn/module/download/downfile.jsp?classid=0&filename=872a26b9183a4aaaa30d01e9c1f73c8e.pdf. Accessed 26 Jan 2020.

  39. 39.

    Beijing medicine sunshine purchasing. https://yp.bjmbc.org.cn/view/index/guide.html. Accessed 26 Jan 2020.

  40. 40.

    YaoZh. Inquiry of drug bid information. https://www.db.yaozh.com/yaopinzhongbiao. Accessed 26 Jan 2020.

  41. 41.

    YaoZh. Drug instruction. https://www.db.yaozh.com/instruct. Accessed 26 Jan 2020.

  42. 42.

    Beijing Municipal Development and Reform Commission. Beijing medical service price inquiry. https://www.fgw.beijing.gov.cn/bjpc/mediprice/MedicalService1.jsp. Accessed 15 Jul 2019.

  43. 43.

    Price Bureau of Jiangsu Province. Provincial Bureau of Health and Family Planning, Provincial Department of Human Resources and Social Security, Provincial Department of Finance. Notice on the implementation plan for comprehensive reform of medical price in public hospitals in Ning Province. https://www.jswjj.gov.cn/office_new/eo_comm_zxnrxs.php. Accessed 15 July 2019.

  44. 44.

    Shanghai Municipal Development and Reform Commission. Shanghai medical institutions medical service projects and price compilation (2014). https://www.shdrc.gov.cn/fzgggz/jggl/jgjgdt/19898.htm. Accessed 15 July 2019.

  45. 45.

    Di MZ, Cao Y, Huang H, et al. Investigation on the expenses of 248 adult patients with community-acquired pneumonia in Dongcheng District, Beijing. Modern Prev Med. 2014;41(14):2560–2 (2584).

    Google Scholar 

  46. 46.

    Wang HZ, Wu M. A study on direct economic burden of herpes zoster patients in Xi Cheng District of Beijing. Int J Virol. 2017;24(4):242–7.

    Google Scholar 

  47. 47.

    Wang Q, Wang LX, Li RZ, et al. Analysis of the medical expenses and economic burden of pulmonary tuberculosis patients in three cities. Chin J Antituberc. 2013;35(4):240–5.

    Google Scholar 

  48. 48.

    Tanno M, Nakamura I, Ito K, et al. Modeling and cost-effectiveness analysis of etanercept in adults with rheumatoid arthritis in Japan: a preliminary analysis. Mod Rheumatol. 2006;16(2):77–84.

    PubMed  Google Scholar 

  49. 49.

    Boye KS, Matza LS, Walter KN, et al. Utilities and disutilities for attributes of injectable treatments for type 2 diabetes. Eur J Health Econ. 2011;12(3):219–30.

    PubMed  Google Scholar 

  50. 50.

    Robinson LA, Hammitt JK, Chang AY, et al. Understanding and improving the one and three times GDP per capita cost-effectiveness thresholds. Health Policy Plan. 2017;32(1):141–5.

    PubMed  Google Scholar 

  51. 51.

    The World Bank. GDP per capita (current US$): China. https://www.data.worldbank.org/indicator/NY.GDP.PCAP.CD?locations=CN. Accessed 16 June 2020.

  52. 52.

    Task Group of the Chinese Guidelines for Pharmacoeconomic Evaluations. China guidelines for pharmacoeconomic evaluations. Chin J Pharm Econ. 2011;6(3):7–48.

    Google Scholar 

  53. 53.

    Shi ZC, Fei HP, Wang ZL. Cost-effectiveness analysis of etanercept plus methotrexate vs triple therapy in treating Chinese rheumatoid arthritis patients. Medicine (Baltimore). 2020;99(3):e16635.

    Google Scholar 

  54. 54.

    Tian F, Li JY, Wen ZH, et al. A novel etanercept biosimilar Anbainuo plus methotrexate exhibits increased cost-effectiveness compared to conventional disease-modifying anti-rheumatic drugs in treating rheumatoid arthritis patients. Medicine (Baltimore). 2019;98(48):e17750.

    CAS  Google Scholar 

  55. 55.

    Chen DY, Hsu PN, Tang CH, et al. Tofacitinib in the treatment of moderate-to-severe rheumatoid arthritis: a cost-effectiveness analysis compared to adalimumab in Taiwan. J Med Econ. 2019;22(8):777–87.

    PubMed  Google Scholar 

  56. 56.

    Li J, Wen Z, Cai A, et al. Real-world cost-effectiveness of infliximab for moderate-to-severe rheumatoid arthritis in a medium-sized city of China. J Comp Eff Res. 2017;6(3):205–18.

    PubMed  Google Scholar 

  57. 57.

    Zhao Y, Li SP, Liu L, et al. Does the choice of tariff matter? A comparison of EQ-5D-5L utility scores using Chinese, UK, and Japanese tariffs on patients with psoriasis vulgaris in Central South China. Medicine (Baltimore). 2017;96(34):e7840.

    Google Scholar 

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Acknowledgements

The authors thank Dr. David Gold and Ms. Ming-Ann Hsu from Pfizer, Inc. for their critical review of the manuscript.

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Authors

Contributions

LT and XM constructed the model, collected and analyzed the data, and drafted the manuscript. QG provided advice on constructing the model from a clinical perspective. LW collected the data. AM was the guarantor of the study and contributed to the design of the study and the analysis and interpretation of the data. YC and PD conceptualized the study and contributed to the revision of the manuscript. All authors gave final approval for the version to be published.

Corresponding author

Correspondence to Aixia Ma.

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Funding

This study was funded by Pfizer Investment Co. Ltd (Beijing, China).

Conflict of interest

Yixi Chen and Peng Dong are employees of Pfizer Investment Co. Ltd (Beijing, China). Lei Tian, Xiaomo Xiong, Qiang Guo, Luying Wang, and Aixia Ma have no conflicts of interest that are directly relevant to the content of this article.

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Availability of data and material

The authors declare that all data other than market shares of tumor necrosis factor inhibitors in the study are publicly available from the literature, conference abstracts, and governmental public sources as listed in the references section. The data of market shares of tumor necrosis factor inhibitors were provided by Pfizer Investment Co. Ltd (Beijing, China). The Excel models used for the analysis can be provided on reasonable request.

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Tian, L., Xiong, X., Guo, Q. et al. Cost-Effectiveness of Tofacitinib for Patients with Moderate-to-Severe Rheumatoid Arthritis in China. PharmacoEconomics (2020). https://doi.org/10.1007/s40273-020-00961-z

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