Advances in Therapy

, Volume 33, Issue 5, pp 807–823 | Cite as

Economic Burden of Switching to a Non-Tumor Necrosis Factor Inhibitor Versus a Tumor Necrosis Factor Inhibitor Biologic Therapy among Patients with Rheumatoid Arthritis

  • Zheng-Yi Zhou
  • Jenny Griffith
  • Ella Xiaoyan Du
  • Daniel Chin
  • Keith A. Betts
  • Arijit Ganguli
Original Research



The objective of this study was to examine healthcare resource utilization (HRU) and costs associated with switching to another tumor necrosis factor alpha inhibitor (TNFi) therapy versus a non-TNFi therapy among patients with rheumatoid arthritis (RA) discontinuing use of an initial TNFi biologic therapy.


Patients with ≥2 RA diagnoses who used ≥1 TNFi on or after their initial RA diagnosis were identified in a US employer-based insurance claims database. Patients were selected based on ≥1 claim of another TNFi or a non-TNFi biologic therapy (occurring after 2010, and within 30 days before to 60 days after discontinuation of the initial TNFi), and continuous insurance ≥6 months before (baseline period) and ≥12 months after the switch date (study period). Patient demographic and clinical characteristics were measured during the baseline period. All-cause and RA-related HRU and costs were analyzed during the 12-month study period using multivariable regression analysis controlling for baseline characteristics and selected comorbidities.


Of the 1577 patients with RA that switched therapies, 1169 patients used another TNFi and 408 patients used a non-TNFi biologic. The most commonly used initial TNFi treatments were etanercept (50%) and adalimumab (34%) among the TNFi cohort, and infliximab (39%) and etanercept (28%) among the non-TNFi cohort. The TNFi cohort had significantly fewer outpatient visits [all-cause: 23.01 vs. 29.77 visits/patient/year; adjusted incidence rate ratio (IRR) = 0.78, P < 0.001; RA-related: 7.42 vs. 13.58; adjusted IRR = 0.58, P < 0.001] and rheumatologist visits (all-cause: 4.01 vs. 6.81; adjusted IRR = 0.66, P < 0.001; RA-related: 3.23 vs. 6.40; adjusted IRR = 0.58, P < 0.001) than the non-TNFi cohort. All-cause total costs were significantly lower for patients who switched to another TNFi instead of a non-TNFi therapy ($36,932 vs. $44,566; adjusted difference = $7045, P < 0.01), as were total RA-related costs ($26,973 vs. $31,735; adjusted difference = $4904, P < 0.01).


Adult patients with RA discontinuing TNFi therapy who switched to an alternative TNFi incurred lower healthcare costs than patients who switched to a non-TNFi biologic.


AbbVie, Inc.


Biologic therapy switching Economic burden Healthcare utilization Healthcare costs Non-tumor necrosis factor inhibitor Rheumatoid arthritis Rheumatology Tumor necrosis factor alpha inhibitor 



Funding for this research was provided by AbbVie, Inc. The article processing charges for this publication were funded by AbbVie, Inc. The study sponsor was involved in all stages of the study research and manuscript preparation, but all authors participated in the design of the study and contributed to the manuscript development. Data were collected by Analysis Group, Inc. and analyzed and interpreted in collaboration with all other authors. All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this manuscript, vouch for the accuracy and completeness of the data reported and the adherence of the study to the protocol, and collectively made the decision to submit the manuscript for publication. Manuscript drafts were prepared by the authors with editorial assistance from a professional medical writer, Shelley Batts, Ph.D., an employee of Analysis Group, Inc., and ultimately paid for by the sponsor, AbbVie, Inc. We would like to thank Cheryl Xiang and Sneha Kelkar of Analysis Group, Inc. for assisting with the data analysis. A synopsis of the current research was presented in poster format at the 2015 American College of Rheumatology Annual Meeting in San Francisco during November 6–11, 2015.


Zheng-Yi Zhou is an employee of Analysis Group, Inc. Jenny Griffith is an employee of AbbVie, Inc. and owns stock/stock options. Ella Xiaoyan Du is an employee of Analysis Group, Inc. Daniel Chin is an employee of AbbVie, Inc. and owns stock/stock options. Keith A. Betts is an employee of Analysis Group, Inc. Arijit Ganguli is an employee of AbbVie, Inc. and owns stock/stock options. Analysis Group, Inc. has received consultancy fees from AbbVie, Inc.

Compliance with Ethics Guidelines

This article does not contain any new studies with human or animal subjects performed by any of the authors. All patient claims information was de-identified to comply with HIPAA, and thus did not require review board approval.


  1. 1.
    Choy EH, Panayi GS. Cytokine pathways and joint inflammation in rheumatoid arthritis. N Engl J Med. 2001;344:907–16.CrossRefPubMedGoogle Scholar
  2. 2.
    Tobon GJ, Youinou P, Saraux A. The environment, geo-epidemiology, and autoimmune disease: rheumatoid arthritis. J Autoimmun. 2010;35:10–4.CrossRefPubMedGoogle Scholar
  3. 3.
    Kvien TK. Epidemiology and burden of illness of rheumatoid arthritis. PharmacoEconomics. 2004;22:1–12.CrossRefPubMedGoogle Scholar
  4. 4.
    Helmick CG, Felson DT, Lawrence RC, et al. Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part I. Arthritis Rheum. 2008;58:15–25.CrossRefPubMedGoogle Scholar
  5. 5.
    Myasoedova E, Crowson CS, Kremers HM, Therneau TM, Gabriel SE. Is the incidence of rheumatoid arthritis rising?: results from Olmsted County, Minnesota, 1955–2007. Arthritis Rheum. 2010;62:1576–82.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    American College of Rheumatology Subcommittee on Rheumatoid Arthritis G. Guidelines for the management of rheumatoid arthritis: 2002 update. Arthritis Rheum. 2002;46:328–46.CrossRefGoogle Scholar
  7. 7.
    Birnbaum H, Pike C, Kaufman R, et al. Societal cost of rheumatoid arthritis patients in the US. Curr Med Res Opin. 2010;26:77–90.CrossRefPubMedGoogle Scholar
  8. 8.
    Mewar D, Wilson AG. Treatment of rheumatoid arthritis with tumour necrosis factor inhibitors. Br J Pharmacol. 2011;162:785–91.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Keystone EC, Kavanaugh AF, Sharp JT, et al. Radiographic, clinical, and functional outcomes of treatment with adalimumab (a human anti-tumor necrosis factor monoclonal antibody) in patients with active rheumatoid arthritis receiving concomitant methotrexate therapy: a randomized, placebo-controlled, 52-week trial. Arthritis Rheum. 2004;50:1400–11.CrossRefPubMedGoogle Scholar
  10. 10.
    St Clair EW, van der Heijde DM, Smolen JS, et al. Combination of infliximab and methotrexate therapy for early rheumatoid arthritis: a randomized, controlled trial. Arthritis Rheum. 2004;50:3432–43.CrossRefPubMedGoogle Scholar
  11. 11.
    Klareskog L, van der Heijde D, de Jager JP, et al. Therapeutic effect of the combination of etanercept and methotrexate compared with each treatment alone in patients with rheumatoid arthritis: double-blind randomised controlled trial. Lancet. 2004;363:675–81.CrossRefPubMedGoogle Scholar
  12. 12.
    Ruiz Garcia V, Jobanputra P, Burls A, et al. Certolizumab pegol (CDP870) for rheumatoid arthritis in adults. Cochrane Database Syst Rev. 2011;18:CD007649.Google Scholar
  13. 13.
    Keystone E, Genovese MC, Klareskog L, et al. Golimumab in patients with active rheumatoid arthritis despite methotrexate therapy: 52-week results of the GO-FORWARD study. Ann Rheum Dis. 2010;69:1129–35.CrossRefPubMedGoogle Scholar
  14. 14.
    Singh JA, Christensen R, Wells GA, et al. A network meta-analysis of randomized controlled trials of biologics for rheumatoid arthritis: a Cochrane overview. CMAJ Can Med Association J Journal de l’Association Medicale Canadienne. 2009;181:787–96.CrossRefGoogle Scholar
  15. 15.
    Feldmann M, Maini RN. Anti-TNF therapy, from rationale to standard of care: what lessons has it taught us? J Immunol. 2010;185:791–4.CrossRefPubMedGoogle Scholar
  16. 16.
    Rubbert-Roth A, Finckh A. Treatment options in patients with rheumatoid arthritis failing initial TNF inhibitor therapy: a critical review. Arthritis Res Ther. 2009;11(Suppl 1):S1.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Karlsson JA, Kristensen LE, Kapetanovic MC, et al. Treatment response to a second or third TNF-inhibitor in RA: results from the South Swedish Arthritis Treatment Group Register. Rheumatology (Oxford). 2008;47:507–13.CrossRefGoogle Scholar
  18. 18.
    Tang B, Rahman M, Waters HC, Callegari P. Treatment persistence with adalimumab, etanercept, or infliximab in combination with methotrexate and the effects on health care costs in patients with rheumatoid arthritis. Clin Ther. 2008;30:1375–84.CrossRefPubMedGoogle Scholar
  19. 19.
    Keystone EC, Breedveld FC, van der Heijde D, et al. Longterm effect of delaying combination therapy with tumor necrosis factor inhibitor in patients with aggressive early rheumatoid arthritis: 10-year efficacy and safety of adalimumab from the randomized controlled PREMIER trial with open-label extension. J Rheumatol. 2014;41:5–14.CrossRefPubMedGoogle Scholar
  20. 20.
    Buch MH, Bingham SJ, Bejarano V, et al. Therapy of patients with rheumatoid arthritis: outcome of infliximab failures switched to etanercept. Arthritis Rheum. 2007;57:448–53.CrossRefPubMedGoogle Scholar
  21. 21.
    Gomez-Reino JJ, Carmona L, Group B. Switching TNF antagonists in patients with chronic arthritis: an observational study of 488 patients over a four-year period. Arthritis Res Ther. 2006;8:R29.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Rotar Z, Hocevar A, Rebolj Kodre A, et al. Retention of the second-line biologic disease-modifying antirheumatic drugs in patients with rheumatoid arthritis failing one tumor necrosis factor alpha inhibitor: data from the registry. Clin Rheumatol. 2015;34:1787–93.CrossRefPubMedGoogle Scholar
  23. 23.
    Harnett J, Wiederkehr D, Gerber R, et al. Real-world evaluation of TNF-inhibitor utilization in rheumatoid arthritis. J Med Econ. 2016;19:91–102.CrossRefPubMedGoogle Scholar
  24. 24.
    Lloyd S, Bujkiewicz S, Wailoo AJ, Sutton AJ, Scott D. The effectiveness of anti-TNF-alpha therapies when used sequentially in rheumatoid arthritis patients: a systematic review and meta-analysis. Rheumatology (Oxford). 2010;49:2313–21.CrossRefGoogle Scholar
  25. 25.
    Gartlehner G, Hansen RA, Jonas BL, Thieda P, Lohr KN. The comparative efficacy and safety of biologics for the treatment of rheumatoid arthritis: a systematic review and metaanalysis. J Rheumatol. 2006;33:2398–408.PubMedGoogle Scholar
  26. 26.
    Malottki K, Barton P, Tsourapas A, et al. Adalimumab, etanercept, infliximab, rituximab and abatacept for the treatment of rheumatoid arthritis after the failure of a tumour necrosis factor inhibitor: a systematic review and economic evaluation. Health Technol Assess. 2011;15:1–278.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Cohen SB, Emery P, Greenwald MW, et al. Rituximab for rheumatoid arthritis refractory to anti-tumor necrosis factor therapy: results of a multicenter, randomized, double-blind, placebo-controlled, phase III trial evaluating primary efficacy and safety at twenty-four weeks. Arthritis Rheum. 2006;54:2793–806.CrossRefPubMedGoogle Scholar
  28. 28.
    Emery P, Keystone E, Tony HP, et al. IL-6 receptor inhibition with tocilizumab improves treatment outcomes in patients with rheumatoid arthritis refractory to anti-tumour necrosis factor biologicals: results from a 24-week multicentre randomised placebo-controlled trial. Ann Rheum Dis. 2008;67:1516–23.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Smolen JS, Kay J, Doyle M, et al. Golimumab in patients with active rheumatoid arthritis after treatment with tumor necrosis factor alpha inhibitors: findings with up to five years of treatment in the multicenter, randomized, double-blind, placebo-controlled, phase 3 GO-AFTER study. Arthritis Res Ther. 2015;17:14.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Kim HL, Lee MY, Park SY, et al. Comparative effectiveness of cycling of tumor necrosis factor-alpha (TNF-alpha) inhibitors versus switching to non-TNF biologics in rheumatoid arthritis patients with inadequate response to TNF-alpha inhibitor using a Bayesian approach. Arch Pharm Res. 2014;37:662–70.CrossRefPubMedGoogle Scholar
  31. 31.
    Devine EB, Alfonso-Cristancho R, Sullivan SD. Effectiveness of biologic therapies for rheumatoid arthritis: an indirect comparisons approach. Pharmacotherapy. 2011;31:39–51.CrossRefPubMedGoogle Scholar
  32. 32.
    Singh JA, Saag KG, Bridges SL Jr, et al. 2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Rheumatol. 2015;68(1):1–26.Google Scholar
  33. 33.
    Hyrich KL, Lunt M, Dixon WG, et al. Effects of switching between anti-TNF therapies on HAQ response in patients who do not respond to their first anti-TNF drug. Rheumatology (Oxford). 2008;47:1000–5.CrossRefGoogle Scholar
  34. 34.
    The United States Food and Drug Administration. Prescribing information- ACTERMA (tocilizumab). 2010.Google Scholar
  35. 35.
    Thaler KJ, Gartlehner G, Kien C, et al. In: Drug class review: targeted immune modulators: final update 3 report. Portland (OR); 2012.Google Scholar
  36. 36.
    [No authors listed]. New drugs/drug news/new medical devices. PT. 2012;37:666–7.Google Scholar
  37. 37.
    Baser O, Ganguli A, Roy S, Xie L, Cifaldi M. Impact of switching from an initial tumor necrosis factor inhibitor on health care resource utilization and costs among patients with rheumatoid arthritis. Clin Ther. 2015;37:1454–65.CrossRefPubMedGoogle Scholar
  38. 38.
    Hansen L, Chang S. Health research data for the real world: the MarketScan Databases.; 2011. Accessed 29 Sept 2015.
  39. 39.
    Romano PS, Roos LL, Jollis JG. Adapting a clinical comorbidity index for use with ICD-9-CM administrative data: differing perspectives. J Clin Epidemiol. 1993;46:1075–9 (discussion 1081–1090).CrossRefPubMedGoogle Scholar
  40. 40.
    Dougados M, Soubrier M, Antunez A, et al. Prevalence of comorbidities in rheumatoid arthritis and evaluation of their monitoring: results of an international, cross-sectional study (COMORA). Ann Rheum Dis. 2014;73:62–8.CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Silman AJ, Pearson JE. Epidemiology and genetics of rheumatoid arthritis. Arthritis Res. 2002;4(Suppl 3):S265–72.CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Kimball AB, Guerin A, Tsaneva M, et al. Economic burden of comorbidities in patients with psoriasis is substantial. J Eur Acad Dermatol Venereol. 2011;25:157–63.CrossRefPubMedGoogle Scholar
  43. 43.
    Schabert VF, Watson C, Gandra SR, et al. Annual costs of tumor necrosis factor inhibitors using real-world data in a commercially insured population in the United States. J Med Econ. 2012;15:264–75.CrossRefPubMedGoogle Scholar
  44. 44.
    McBride S, Sarsour K, White LA, et al. Biologic disease-modifying drug treatment patterns and associated costs for patients with rheumatoid arthritis. J Rheumatol. 2011;38:2141–9.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Healthcare 2016

Authors and Affiliations

  1. 1.Analysis Group, Inc.New YorkUSA
  2. 2.AbbVie, Inc.North ChicagoUSA
  3. 3.Analysis Group, Inc.Los AngelesUSA

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