Skip to main content

The value of persistence in treatment with subcutaneous TNF-alpha inhibitors for ankylosing spondylitis

Abstract

Objective

To estimate the impact of persistence on cost-effectiveness of subcutaneous tumor necrosis factor-α inhibitors (SC-TNFis) from healthcare and societal perspectives in a United Kingdom ankylosing spondylitis (AS) population using a recently published Markov cohort model.

Methods

A recently published cost-effectiveness model developed for a National Institute for health and Care Excellence appraisal was extended to fit the current study; in brief, it is a Markov cohort model where treatment responders continue from the trial period with maintenance SC-TNFi treatment, while non-responders transition to conventional care. Costs and effects were modeled for a hypothetical SC-TNFi with average efficacy and price. Model outcomes included quality-adjusted life-years (QALYs), total direct and indirect lifetime costs, and incremental cost-effectiveness ratios (ICERs). The cost-effectiveness of SC-TNFi persistence was estimated by decreasing the annual discontinuation probability in five percentage point increments from 25 to 5% per annum.

Results

From a health care perspective, the ICERs for the modeled discontinuation rates compared to the baseline annual discontinuation rate (25%) ranged between GBP 17,277 and GBP 18,161. From a societal perspective, increased discontinuation rates resulted in decreased total costs and higher QALYs; hence, lower discontinuation rates dominated higher discontinuation rates from a societal perspective.

Conclusion

In conclusion, this study shows that, all else equal, higher SC-TNFi treatment persistence in AS is cost effective from a health care perspective and dominant from a societal perspective. Hence, all else equal, prescribing the SC-TNFi with the highest persistence may be considered a cost-effective strategy.

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

Fig. 1
Fig. 2

References

  1. 1.

    Wanders, A., Landewe, R., Dougados, M., Mielants, H., van der Linden, S., van der Heijde, D.: Association between radiographic damage of the spine and spinal mobility for individual patients with ankylosing spondylitis: can assessment of spinal mobility be a proxy for radiographic evaluation? Ann. Rheum. Dis. 64, 988–994 (2005)

    CAS  Article  Google Scholar 

  2. 2.

    Fries, J.F.: Effectiveness and toxicity considerations in outcome directed therapy in rheumatoid arthritis. J. Rheumatol. Suppl. 44, 102–106 (1996)

    CAS  PubMed  Google Scholar 

  3. 3.

    Cooksey, R., Husain, M.J., Brophy, S., Davies, H., Rahman, M.A., Atkinson, M.D., Phillips, C.J., Siebert, S.: The cost of ankylosing spondylitis in the UK using linked routine and patient-reported survey data. PLoS One 10, e0126105 (2015)

    Article  Google Scholar 

  4. 4.

    Dean, L.E., Jones, G.T., MacDonald, A.G., Downham, C., Sturrock, R.D., Macfarlane, G.J.: Global prevalence of ankylosing spondylitis. Rheumatology (Oxford) 53, 650–657 (2014)

    Article  Google Scholar 

  5. 5.

    Blum, M.A., Koo, D., Doshi, J.A.: Measurement and rates of persistence with and adherence to biologics for rheumatoid arthritis: a systematic review. Clin. Ther. 33, 901–913 (2011)

    Article  Google Scholar 

  6. 6.

    van der Heijde, D., Ramiro, S., Landewé, R., Baraliakos, X., Van den Bosch, F., Sepriano, A., Regel, A., Ciurea, A., Dagfinrud, H., Dougados, M.: 2016 update of the ASAS-EULAR management recommendations for axial spondyloarthritis. Ann. Rheum. Dis. 76(6), 978–991 (2017). (Annrheumdis-2016-210770)

    Article  Google Scholar 

  7. 7.

    Souto, A., Maneiro, J.R., Gómez-Reino, J.J.: Rate of discontinuation and drug survival of biologic therapies in rheumatoid arthritis: a systematic review and meta-analysis of drug registries and health care databases. Rheumatology 55, 523–534 (2015)

    PubMed  Google Scholar 

  8. 8.

    Aletaha, D., Smolen, J.S.: Effectiveness profiles and dose dependent retention of traditional disease modifying antirheumatic drugs for rheumatoid arthritis. An observational study. J Rheumatol. 29, 1631–1638 (2002)

    CAS  PubMed  Google Scholar 

  9. 9.

    Pincus, T., Marcum, S.B., Callahan, L.F.: Longterm drug therapy for rheumatoid arthritis in seven rheumatology private practices: II. Second line drugs and prednisone. J. Rheumatol. 19, 1885–1894 (1992)

    CAS  PubMed  Google Scholar 

  10. 10.

    Rothwell, P.M.: External validity of randomised controlled trials:“to whom do the results of this trial apply?”. Lancet 365, 82–93 (2005)

    Article  Google Scholar 

  11. 11.

    Henaux, S., Ruyssen-Witrand, A., Cantagrel, A., Barnetche, T., Fautrel, B., Filippi, N., Lukas, C., Raffeiner, B., Rossini, M., Degboé, Y.: Risk of losing remission, low disease activity or radiographic progression in case of bDMARD discontinuation or tapering in rheumatoid arthritis: systematic analysis of the literature and meta-analysis. Ann. Rheum. Dis. 77(4), 515–522 (2017). (Annrheumdis-2017-212423)

    Article  Google Scholar 

  12. 12.

    Lie, E., van der Heijde, D., Uhlig, T., Mikkelsen, K., Rodevand, E., Koldingsnes, W., Kaufmann, C., Kvien, T.K.: Effectiveness of switching between TNF inhibitors in ankylosing spondylitis: data from the NOR-DMARD register. Ann. Rheum. Dis. 70, 157–163 (2011)

    CAS  Article  Google Scholar 

  13. 13.

    Hughes, D., Cowell, W., Koncz, T., Cramer, J.: Methods for integrating medication compliance and persistence in pharmacoeconomic evaluations. Value health 10, 498–509 (2007)

    Article  Google Scholar 

  14. 14.

    NICE (2016) Single Technology Appraisal. Secukinumab for the treatment of active ankylosing spondylitis in adults who have responded inadequately to conventional therapy [ID719]—Committee papers. National Institute for Health and Care Excellence, UK. https://www.nice.org.uk/guidance/ta407/documents/committee-papers. Accessed 12 Sept 2019

  15. 15.

    Corbett, M., Soares, M., Jhuti, G., et al.: Tumour necrosis factor-alpha inhibitors for ankylosing spondylitis and non-radiographic axial spondyloarthritis: a systematic review and economic evaluation. Health Technol. Assess. 20, 1–334 (2016). (v-vi)

    Article  Google Scholar 

  16. 16.

    Heinonen, A.V., Aaltonen, K.J., Joensuu, J.T., Lahteenmaki, J.P., Pertovaara, M.I., Romu, M.K., Hirvonen, H.E., Simila, A.K., Blom, M.L., Nordstrom, D.C.: Effectiveness and drug survival of TNF inhibitors in the treatment of ankylosing spondylitis: a prospective cohort study. J. Rheumatol. 42, 2339–2346 (2015)

    CAS  Article  Google Scholar 

  17. 17.

    Jeong, H., Eun, Y.H., Kim, I.Y., Kim, H., Ahn, J.K., Lee, J., Koh, E.M., Cha, H.S.: Drug survival of tumor necrosis factor alpha inhibitors in patients with ankylosing spondylitis in Korea. Korean J. Intern. Med. 33, 407–416 (2018)

    Article  Google Scholar 

  18. 18.

    Ruwaard, J., l’Ami, M.J., Marsman, A.F., Kneepkens, E.L., van Denderen, J.C., van der Horst-Bruinsma, I.E., Nurmohamed, M.T., Wolbink, G.: Comparison of drug survival and clinical outcome in patients with ankylosing spondylitis treated with etanercept or adalimumab. Scand. J. Rheumatol. 47, 122–126 (2018)

    CAS  Article  Google Scholar 

  19. 19.

    Bakland, G., Gran, J.T., Nossent, J.C.: Increased mortality in ankylosing spondylitis is related to disease activity. Ann. Rheum. Dis. 70, 1921–1925 (2011)

    Article  Google Scholar 

  20. 20.

    Braun, J., Baraliakos, X., Hermann, K.G., Deodhar, A., van der Heijde, D., Inman, R., Beutler, A., Zhou, Y., Xu, S., Hsu, B.: The effect of two golimumab doses on radiographic progression in ankylosing spondylitis: results through 4 years of the GO-RAISE trial. Ann. Rheum. Dis. 73, 1107–1113 (2014)

    CAS  Article  Google Scholar 

  21. 21.

    van der Heijde, D., Baraliakos, X., Hermann, K.-G.A., Landewé, R.B., Machado, P.M., Maksymowych, W.P., Davies, O.R., de Peyrecave, N., Hoepken, B., Bauer, L.: Limited radiographic progression and sustained reductions in MRI inflammation in patients with axial spondyloarthritis: 4-year imaging outcomes from the RAPID-axSpA phase III randomised trial. Ann. Rheum. Dis. 77, 699–705 (2018)

    Article  Google Scholar 

  22. 22.

    Baraliakos, X., Braun, J., Deodhar, A., Poddubny, D., Emery, P., Delicha, E., Talloczy, Z., Porter, B.: SAT0268 Secukinumab demonstrates low radiographic progression and sustained efficacy through 4 years in patients with active ankylosing spondylitis. BMJ Publishing Group Ltd, London (2018)

    Book  Google Scholar 

  23. 23.

    NICE (2016) TNF-alpha inhibitors for ankylosing spondylitis and non-radiographic axial spondyloarthritis. Technology appraisal guidance TA383, National Institute for Health and Care Excellence, UK. ​https://www.nice.org.uk/guidance/ta383. Accessed 12 Sept 2019

  24. 24.

    Wailoo, A., Hernandez, M., Philips, C., Brophy, S., Siebert, S.: Modeling health state utility values in ankylosing spondylitis: comparisons of direct and indirect methods. Value Health 18, 425–431 (2015)

    Article  Google Scholar 

  25. 25.

    Boonen, A., van der Heijde, D., Landewe, R., et al.: Direct costs of ankylosing spondylitis and its determinants: an analysis among three European countries. Ann. Rheum. Dis. 62, 732–740 (2003)

    CAS  Article  Google Scholar 

  26. 26.

    Rafia, R., Ara, R., Packham, J., Haywood, K.L., Healey, E.: Healthcare costs and productivity losses directly attributable to ankylosing spondylitis. Clin. Exp. Rheumatol. 30, 246–253 (2012)

    PubMed  Google Scholar 

  27. 27.

    McLeod, C., Bagust, A., Boland, A., Dagenais, P., Dickson, R., Dundar, Y., Hill, R.A., Jones, A., Mujica Mota, R., Walley, T.: Adalimumab, etanercept and infliximab for the treatment of ankylosing spondylitis: a systematic review and economic evaluation. Health Technol. Assess. 11(1–158), 3–4 (2007)

    Google Scholar 

  28. 28.

    Cannon, G.W., DuVall, S.L., Haroldsen, C.L., et al.: Clinical outcomes and biologic costs of switching between tumor necrosis factor inhibitors in US veterans with rheumatoid arthritis. Adv Ther 33, 1347–1359 (2016)

    Article  Google Scholar 

  29. 29.

    Dalen, J., Svedbom, A., Black, C.M., Kachroo, S.: Second-line treatment persistence and costs among patients with immune-mediated rheumatic diseases treated with subcutaneous TNF-alpha inhibitors. Rheumatol. Int. 37, 2049–2058 (2017)

    CAS  Article  Google Scholar 

  30. 30.

    Dalen, J., Svedbom, A., Black, C.M., Lyu, R., Ding, Q., Sajjan, S., Sazonov, V., Kachroo, S.: Treatment persistence among patients with immune-mediated rheumatic disease newly treated with subcutaneous TNF-alpha inhibitors and costs associated with non-persistence. Rheumatol. Int. 36, 987–995 (2016)

    CAS  Article  Google Scholar 

  31. 31.

    Rashid, N., Lin, A.T., Aranda Jr., G., Lin, K.J., Guerrero, V.N., Nadkarni, A., Patel, C.: Rates, factors, reasons, and economic impact associated with switching in rheumatoid arthritis patients newly initiated on biologic disease modifying anti-rheumatic drugs in an integrated healthcare system. J. Med. Econ. 19, 568–575 (2016)

    Article  Google Scholar 

  32. 32.

    Svedbom, A., Dalen, J., Black, C.M., Kachroo, S.: Persistence and costs with subcutaneous TNF-alpha inhibitors in immune-mediated rheumatic disease stratified by treatment line. Patient Prefer. Adherence 11, 95–106 (2017)

    Article  Google Scholar 

  33. 33.

    Baraliakos, X., Listing, J., von der Recke, A., Braun, J.: The natural course of radiographic progression in ankylosing spondylitis—evidence for major individual variations in a large proportion of patients. J. Rheumatol. 36, 997–1002 (2009)

    Article  Google Scholar 

  34. 34.

    Gulyas, K., Bodnar, N., Nagy, Z., et al.: Real-life experience with switching TNF-alpha inhibitors in ankylosing spondylitis. Eur. J. Health Econ. 15(Suppl 1), S93–S100 (2014)

    Article  Google Scholar 

  35. 35.

    Machado, M.A., Moura, C.S., Ferre, F., Bernatsky, S., Rahme, E., Acurcio Fde, A.: Treatment persistence in patients with rheumatoid arthritis and ankylosing spondylitis. Rev. Saude Publica 50, 50 (2016)

    PubMed  PubMed Central  Google Scholar 

  36. 36.

    Walsh, J.A., Adejoro, O., Chastek, B., Park, Y.: Treatment patterns of biologics in US patients with ankylosing spondylitis: descriptive analyses from a claims database. J. Comp. Eff. Res. 7, 369–380 (2018)

    Article  Google Scholar 

  37. 37.

    Fagerli, K.M., Kearsley-Fleet, L., Watson, K.D., Packham, J., Contributors Group BR, Symmons, D.P.M., Hyrich, K.L.: Long-term persistence of TNF-inhibitor treatment in patients with psoriatic arthritis. Data from the British Society for Rheumatology Biologics Register. RMD Open 4, e000596 (2018)

    Article  Google Scholar 

  38. 38.

    Drummond, M.F., Sculpher, M.J., Claxton, K., Stoddart, G.L., Torrance, G.W.: Methods for the economic evaluation of health care programmes. Oxford University Press, Oxford (2015)

    Google Scholar 

  39. 39.

    Koopmanschap, M.A., Rutten, F.F., van Ineveld, B.M., Van Roijen, L.: The friction cost method for measuring indirect costs of disease. J. Health. Econ. 14, 171–189 (1995)

    CAS  Article  Google Scholar 

  40. 40.

    Liljas, B.: How to calculate indirect costs in economic evaluations. Pharmacoeconomics 13, 1–7 (1998)

    CAS  Article  Google Scholar 

  41. 41.

    NICE (2014) Interim methods guide for developing service guidance 2014. Process and methods guides no. 8. National Institute for Health and Care Excellence (NICE), London. https://www.ncbi.nlm.nih.gov/pubmed/28230952  

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to Sumesh Kachroo.

Ethics declarations

Conflict of interest

The authors report no other conflicts of interest in this work.

Ethical approval

This study was supported by Merck & Co., Inc. S Kachroo, C Black, and R Borse are employees of Merck & Co., Kenilworth, NJ, USA, and hold stock and options. A Svedbom, J Dalén, M Ivergård, and K Luttropp were paid consultants to Merck through their employment at ICON Clinical Research. ICON Clinical Research has received funding from several pharmaceutical companies involved in the marketing of products for treatment of rheumatic disease.

Human and animal rights

This study was supported by Merck & Co., Inc. Given that the work relies on synthesis of publically available data, the research did not involve human participants and/or animals.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 47 kb)

Supplementary material 2 (DOCX 26 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Svedbom, A., Dalén, J., Ivergård, M. et al. The value of persistence in treatment with subcutaneous TNF-alpha inhibitors for ankylosing spondylitis. Eur J Health Econ 21, 45–54 (2020). https://doi.org/10.1007/s10198-019-01110-w

Download citation

Keywords

  • Cost–benefit analysis
  • Medication persistence
  • Economic evaluation
  • Ankylosing spondylitis
  • Bechterew’s disease

JEL Classification

  • I120