Skip to main content

Advertisement

SpringerLink
Log in

Outcomes of switching anti-TNF drugs in rheumatoid arthritis—a study based on observational data from the Finnish Register of Biological Treatment (ROB-FIN)

  • Original Article
  • Published:
Clinical Rheumatology Aims and scope Submit manuscript

Abstract

The aim of this study was to assess, based on observational data from the Finnish Register of Biological Treatment, the outcomes of switching an initial tumor necrosis factor (TNF) blocker to another in the treatment of rheumatoid arthritis (RA). RA patients, who started biological therapy with a TNF blocker between May 1999 and April 2009 and who switched to another TNF blocker, were studied (n = 479). The outcomes were assessed according to the reason for and type of the switch. Outcome assessments included American College of Rheumatology 50 responder index (ACR50) response at 3 months after the switch, treatment duration of the second TNF blocker, and swollen joint counts, CRP and DAS28 score at the 3 months, best and last observations of the first and second TNF blocker, respectively. In those who switched due to lack of effectiveness (LOE), the disease activity parameters fell significantly from baseline upon use of infliximab or adalimumab, but had increased prior to the switch. Switching to another TNF blocker (etanercept or adalimumab) restored the response initially achieved with the first TNF blocker. The disease activity parameters fell significantly from baseline upon use of etanercept, and were maintained but not further improved after switching to adalimumab. TNF blocker switching seemed to be most beneficial in secondary LOE (defined as loss of ACR50 response). In those who switched due to adverse events (AE) or other reasons, a similar degree of response as had been achieved with the first agent was also achieved and maintained with the second agent. The results suggest that a second TNF blocker can restore the response in cases of secondary LOE and maintain it after switching due to an AE.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Buch MH, Conaghan PG, Quinn MA, Bingham SJ, Veale D, Emery P (2004) True infliximab resistance in rheumatoid arthritis: a role for lymphotoxin alpha? Ann Rheum Dis 63:1344–1346

    Article  PubMed  CAS  Google Scholar 

  2. Klaasen R, Thurlings RM, Wijbrandts CA, van Kuijk AW, Baeten D, Gerlag DM, Tak PP (2009) The relationship between synovial lymphocyte aggregates and the clinical response to infliximab in rheumatoid arthritis: a prospective study. Arthritis Rheum 60:3217–3224

    Article  PubMed  CAS  Google Scholar 

  3. Tracey D, Klareskog L, Sasso EH, Salfeld JG, Tak PP (2008) Tumor necrosis factor antagonist mechanisms of action: a comprehensive review. Pharmacol Ther 117:244–279

    Article  PubMed  CAS  Google Scholar 

  4. Mpofu S, Fatima F, Moots RJ (2005) Anti-TNF-alpha therapies: they are all the same (aren’t they?). Rheumatology (Oxford) 44:271–273

    Article  CAS  Google Scholar 

  5. Lutt JR, Deodhar A (2008) Rheumatoid arthritis: strategies in the management of patients showing an inadequate response to TNFalpha antagonists. Drugs 68:591–606

    Article  PubMed  CAS  Google Scholar 

  6. Furst DE, Keystone EC, Fleischmann R, Mease P, Breedveld FC, Smolen JS, Kalden JR, Braun J, Bresnihan B, Burmester GR, De Benedetti F, Dörner T, Emery P, Gibofsky A, Kavanaugh A, Kirkham B, Schiff MH, Sieper J, Singer N, Van Riel PL, Weinblatt ME, Weisman MH, Winthrop K (2010) Updated consensus statement on biological agents for the treatment of rheumatic diseases, 2009. Ann Rheum Dis 69(Suppl 1):i2–i29

    Article  PubMed  CAS  Google Scholar 

  7. van Vollenhoven R, Harju A, Brannemark S, Klareskog L (2003) Treatment with infliximab (Remicade) when etanercept (Enbrel) has failed or vice versa: data from the STURE registry showing that switching tumour necrosis factor alpha blockers can make sense. Ann Rheum Dis 62:1195–1198

    Article  PubMed  Google Scholar 

  8. Brocq O, Albert C, Roux C, Gerard D, Breuil V, Ziegler LE (2004) Adalimumab in rheumatoid arthritis after failed infliximab and/or etanercept therapy: experience with 18 patients. Joint Bone Spine 71:601–603

    Article  PubMed  CAS  Google Scholar 

  9. Yazici Y, Erkan D (2004) Do etanercept-naive patients with rheumatoid arthritis respond better to infliximab than patients for whom etanercept has failed? Ann Rheum Dis 63:607–608

    PubMed  CAS  Google Scholar 

  10. Cohen G, Courvoisier N, Cohen JD, Zaltni S, Sany J, Combe B (2005) The efficiency of switching from infliximab to etanercept and vice-versa in patients with rheumatoid arthritis. Clin Exp Rheumatol 23:795–800

    PubMed  CAS  Google Scholar 

  11. Wick MC, Ernestam S, Lindblad S, Bratt J, Klareskog L, van Vollenhoven RF (2005) Adalimumab (Humira) restores clinical response in patients with secondary loss of efficacy from infliximab (Remicade) or etanercept (Enbrel): results from the STURE registry at Karolinska University Hospital. Scand J Rheumatol 34:353–358

    Article  PubMed  CAS  Google Scholar 

  12. Gomez-Reino JJ, Carmona L (2006) Switching TNF antagonists in patients with chronic arthritis: an observational study of 488 patients over a four-year period. Arthritis Res Ther 8:R29

    Article  PubMed  Google Scholar 

  13. Nikas SN, Voulgari PV, Alamanos Y, Papadopoulos CG, Venetsanopoulos AI, Georgiadis AN, Drosos AA (2006) Efficacy and safety of switching from infliximab to adalimumab: a comparative controlled study. Ann Rheum Dis 65:257–260

    Article  PubMed  CAS  Google Scholar 

  14. Solau-Gervais E, Laxenaire N, Cortet B, Dubucquoi S, Duquesnoy B, Flipo RM (2006) Lack of efficacy of a third tumour necrosis factor alpha antagonist after failure of a soluble receptor and a monoclonal antibody. Rheumatology (Oxford) 45:1121–1124

    Article  CAS  Google Scholar 

  15. Bombardieri S, Ruiz AA, Fardellone P, Geusens P, McKenna F, Unnebrink K, Oezer U, Kary S, Kupper H, Burmester GR, Research in Active Rheumatoid Arthritis (ReAct) Study Group (2007) Effectiveness of adalimumab for rheumatoid arthritis in patients with a history of TNF-antagonist therapy in clinical practice. Rheumatology (Oxford) 46:1191–1199

    Article  CAS  Google Scholar 

  16. Buch MH, Bingham SJ, Bejarano V, Bryer D, White J, Reece R, Quinn M, Emery P (2007) Therapy of patients with rheumatoid arthritis: outcome of infliximab failures switched to etanercept. Arthritis Rheum 57:448–453

    Article  PubMed  CAS  Google Scholar 

  17. Di Poi E, Perin A, Morassi MP, Del Frate M, Ferraccioli GF, De Vita S (2007) Switching to etanercept in patients with rheumatoid arthritis with no response to infliximab. Clin Exp Rheumatol 25:85–87

    PubMed  Google Scholar 

  18. Furst DE, Gaylis N, Bray V, Olech E, Yocum D, Ritter J, Weisman M, Wallace DJ, Crues J, Khanna D, Eckel G, Yeilding N, Callegari P, Visvanathan S, Rojas J, Hegedus R, George L, Mamun K, Gilmer K, Troum O (2007) Open-label, pilot protocol of patients with rheumatoid arthritis who switch to infliximab after an incomplete response to etanercept: the opposite study. Ann Rheum Dis 66:893–899

    Article  PubMed  CAS  Google Scholar 

  19. Hjardem E, Østergaard M, Pødenphant J, Tarp U, Andersen LS, Bing J, Peen E, Lindegaard HM, Ringsdal VS, Rødgaard A, Skøt J, Hansen A, Mogensen HH, Unkerskov J, Hetland ML (2007) Do rheumatoid arthritis patients in clinical practice benefit from switching from infliximab to a second tumor necrosis factor alpha inhibitor? Ann Rheum Dis 66:1184–1189

    Article  PubMed  CAS  Google Scholar 

  20. Hyrich KL, Lunt M, Watson KD, Symmons DP, Silman AJ (2007) Outcomes after switching from one anti-tumor necrosis factor alpha agent to a second anti-tumor necrosis factor alpha agent in patients with rheumatoid arthritis: results from a large UK national cohort study. Arthritis Rheum 56:13–20

    Article  PubMed  CAS  Google Scholar 

  21. Iannone F, Trotta F, Montecucco C, Giacomelli R, Galeazzi M, Matucci-Cerinic M, Ferri C, Cutolo M, Maria Bambara L, Triolo G, Ferraccioli G, Valentini G, Lapadula G (2007) Etanercept maintains the clinical benefit achieved by infliximab in patients with rheumatoid arthritis who discontinued infliximab because of side effects. Ann Rheum Dis 66:249–252

    Article  PubMed  CAS  Google Scholar 

  22. Karlsson JA, Kristensen LE, Kapetanovic MC, Gülfe A, Saxne T, Geborek P (2008) Treatment response to a second or third TNF-inhibitor in RA: results from the South Swedish Arthritis Treatment Group Register. Rheumatology (Oxford) 47:507–513

    Article  CAS  Google Scholar 

  23. Blom M, Kievit W, Fransen J, Kuper IH, den Broeder AA, De Gendt CM, Jansen TL, Brus HL, van de Laar MA, van Riel PL (2009) The reason for discontinuation of the first tumor necrosis factor (TNF) blocking agent does not influence the effect of a second TNF blocking agent in patients with rheumatoid arthritis. J Rheumatol 36:2171–2177

    Article  PubMed  CAS  Google Scholar 

  24. Conti F, Scrivo R, Spinelli FR, Truglia S, Magrini L, Di Franco M, Ceccarelli F, Valesini G (2009) Outcome in patients with rheumatoid arthritis switching TNF-alpha antagonists: a single center, observational study over an 8-year period. Clin Exp Rheumatol 27:540–541

    PubMed  CAS  Google Scholar 

  25. Smolen JS, Kay J, Doyle MK, Landewé R, Matteson EL, Wollenhaupt J, Gaylis N, Murphy FT, Neal JS, Zhou Y, Visvanathan S, Hsia EC, Rahman MU, for the GO-AFTER study investigators (2009) Golimumab in patients with active rheumatoid arthritis after treatment with tumour necrosis factor alpha inhibitors (GO-AFTER study): a multicentre, randomised, double-blind, placebo-controlled, phase III trial. Lancet 374:210–221

    Article  PubMed  CAS  Google Scholar 

  26. Konttinen L, Honkanen V, Uotila T, Pöllänen J, Waahtera M, Romu M, Puolakka K, Vasala M, Karjalainen A, Luukkainen R, Nordström DC (2006) Biological treatment in rheumatic diseases: results from a longitudinal surveillance: adverse events. Rheumatol Int 26:916–922

    Article  PubMed  CAS  Google Scholar 

  27. Konttinen L, Kankaanpää E, Luosujärvi R, Blåfield H, Vuori K, Hakala M, Rantalaiho V, Savolainen E, Uutela T, Nordström D (2006) Effectiveness of anakinra in rheumatic disease in patients naive to biological drugs or previously on TNF blocking drugs: an observational study. Clin Rheumatol 25:882–884

    Article  PubMed  Google Scholar 

  28. Nordström DC, Konttinen L, Korpela M, Tiippana-Kinnunen T, Eklund K, Forsberg S, Ilva K, Kaipiainen-Seppänen O, Malmi T, Ylä-Kerttula T, Honkanen V (2006) Classic disease modifying anti-rheumatic drugs (DMARDs) in combination with infliximab. The Finnish experience. Rheumatol Int 26:741–748

    Article  PubMed  Google Scholar 

  29. Konttinen L, Tuompo R, Uusitalo T, Luosujärvi R, Laiho K, Lähteenmäki J, Puurtinen-Vilkki M, Lanteri R, Kortelainen S, Karilainen H, Varjolahti-Lehtinen T, Nordström D (2007) Anti-TNF therapy in the treatment of ankylosing spondylitis: the Finnish experience; ROB-FIN Study Group. Clin Rheumatol 26:1693–1700

    Article  PubMed  Google Scholar 

  30. Virkki LM, Konttinen YT, Peltomaa R, Suontama K, Saario R, Immonen K, Jäntti J, Tuomiranta T, Nykänen P, Hämeenkorpi R, Heikkilä S, Isomäki P, Nordström D (2008) Cost-effectiveness of infliximab in the treatment of rheumatoid arthritis in clinical practice. Clin Exp Rheumatol 26:1059–1066

    PubMed  CAS  Google Scholar 

  31. Virkki LM, Sumathikutty BC, Aarnio M, Valleala H, Heikkilä R, Kauppi M, Karstila K, Pirilä L, Ekman P, Salomaa S, Romu M, Seppälä J, Niinisalo H, Konttinen YT, Nordström DC (2010) Biological therapy for psoriatic arthritis in clinical practice: outcomes up to 2 years. J Rheumatol 37:2362–2368

    Article  PubMed  Google Scholar 

  32. Hakala M, Hannonen P, Helve T, Korpela M, Mattila K, Möttonen T, Varis T (updated 2009) Rheumatoid arthritis. Current Care guideline 2003. www.kaypahoito.fi. Accessed 14 Apr 2011

  33. Haraoui B, Keystone EC, Thorne JC, Pope JE, Chen I, Asare CG, Leff JA (2004) Clinical outcomes of patients with rheumatoid arthritis after switching from infliximab to etanercept. J Rheumatol 31:2356–2359

    PubMed  CAS  Google Scholar 

  34. Wolbink GJ, Vis M, Lems W, Voskuyl AE, de Groot E, Nurmohamed MT, Stapel S, Tak PP, Aarden L, Dijkmans B (2006) Development of antiinfliximab antibodies and relationship to clinical response in patients with rheumatoid arthritis. Arthritis Rheum 54:711–715

    Article  PubMed  Google Scholar 

  35. Buch MH, Bingham SJ, Bryer D, Emery P (2007) Long-term infliximab treatment in rheumatoid arthritis: subsequent outcome of initial responders. Rheumatology (Oxford) 46:1153–1156

    Article  CAS  Google Scholar 

  36. Bendtzen K, Geborek P, Svenson M, Larsson L, Kapetanovic MC, Saxne T (2006) Individualized monitoring of drug bioavailability and immunogenicity in rheumatoid arthritis patients treated with the tumor necrosis factor alpha inhibitor infliximab. Arthritis Rheum 54:3782–3789

    Article  PubMed  CAS  Google Scholar 

  37. Radstake TR, Svenson M, Eijsbouts AM, van den Hoogen FH, Enevold C, van Riel PL, Bendtzen K (2009) Formation of antibodies against infliximab and adalimumab strongly correlates with functional drug levels and clinical responses in rheumatoid arthritis. Ann Rheum Dis 68:1739–1745

    Article  PubMed  CAS  Google Scholar 

  38. van der Bijl AE, Breedveld FC, Antoni CE, Kalden JR, Kary S, Burmester GR, Beckmann C, Unnebrink K, Kupper H (2008) An open-label pilot study of the effectiveness of adalimumab in patients with rheumatoid arthritis and previous infliximab treatment: relationship to reasons for failure and anti-infliximab antibody status. Clin Rheumatol 27:1021–1028

    Article  PubMed  Google Scholar 

  39. Bartelds GM, Wijbrandts CA, Nurmohamed MT, Stapel S, Lems WF, Aarden L, Dijkmans BA, Tak PP, Wolbink GJ (2007) Clinical response to adalimumab: relationship to anti-adalimumab antibodies and serum adalimumab concentrations in rheumatoid arthritis. Ann Rheum Dis 66:921–926

    Article  PubMed  CAS  Google Scholar 

  40. Rozin AP (2004) Infliximab efficiency and failure. Ann Rheum Dis 63:751–752

    Article  PubMed  CAS  Google Scholar 

  41. Anderson PJ (2005) Tumor necrosis factor inhibitors: clinical implications of their different immunogenicity profiles. Semin Arthritis Rheum 34(Suppl 1):19–22

    Article  PubMed  CAS  Google Scholar 

  42. Bartelds GM, Wijbrandts CA, Nurmohamed MT, Stapel S, Lems WF, Aarden L, Dijkmans BA, Tak PP, Wolbink GJ (2010) Anti-infliximab and anti-adalimumab antibodies in relation to response to adalimumab in infliximab switchers and anti-tumour necrosis factor naive patients: a cohort study. Ann Rheum Dis 69:817–821

    Article  PubMed  CAS  Google Scholar 

  43. Smolen JS, Weinblatt ME (2008) When patients with rheumatoid arthritis fail tumour necrosis factor inhibitors: what is the next step? Ann Rheum Dis 67:1497–1498

    Article  PubMed  Google Scholar 

  44. Villeneuve E, Haraoui B (2010) To switch or to change class—the biologic dilemma in rheumatoid arthritis. Nat Rev Rheumatol 6:301–305

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The data processing and statistical assistance by Dr. Viljami Laine and secretarial assistance by Taina Käyhkö are greatly appreciated. This study has been supported by the Victoria Foundation, the Wilhelm and Else Stockmann Foundation, the Waldemar von Frenckell Foundation, Finska Läkaresällskapet, the Perklen Foundation, the Sigrid Jusélius Foundation, the Center of Excellence of the Academy of Finland, ORTON Foundation, EVO grants, and the TBGS National Graduate School of Musculoskeletal Disorders and Biomaterials. The ROB-FIN register has been financially supported by grants from Abbott, Roche, Schering-Plough, UCB, and Wyeth.

Disclosures

Liisa M. Virkki has received an unrestricted research grant for this study from Wyeth.

Author information

Authors and Affiliations

  1. University of Helsinki, PO Box 63, Haartmaninkatu 8, 00014, Helsinki, Finland

    Liisa M. Virkki, Yuya Takakubo, Yrjö T. Konttinen & Dan C. Nordström

  2. Helsinki University Central Hospital, PO Box 700, Haartmaninkatu 8, 00029 HUS, Helsinki, Finland

    Liisa M. Virkki, Heikki Valleala, Heikki Relas, Riitta Koivuniemi, Yrjö T. Konttinen & Dan C. Nordström

  3. ORTON Orthopaedic Hospital of the Invalid Foundation, Tenholantie 10, 00280, Helsinki, Finland

    Yuya Takakubo & Yrjö T. Konttinen

  4. Kuusankoski Regional Hospital, Sairaalankuja 3C, 45750 Sairaalamäki, Kouvola, Finland

    Jorma Vuotila

  5. Riihimäki Regional Hospital, Kontiontie 77, 11120, Riihimäki, Finland

    Riitta Komulainen

  6. Seinäjoki Central Hospital, Hanneksenrinne 7, 60220, Seinäjoki, Finland

    Urpo Yli-Kerttula

  7. Tampere University Hospital, Teiskontie 35, 33520, Tampere, Finland

    Urpo Yli-Kerttula & Susanna Sihvonen

  8. Turku University Central Hospital, Kiinamyllykatu 4–8, 20520, Turku, Finland

    Markku Mali

  9. Mänttä Regional Hospital, Sairaalantie 168, 35800, Mänttä, Finland

    Susanna Sihvonen

  10. Lapland Central Hospital, Ounasrinteentie 22, 96101, Rovaniemi, Finland

    Maija-Liisa Krogerus

  11. Länsi-Pohja Central Hospital, Kauppakatu 25, 94100, Kemi, Finland

    Maija-Liisa Krogerus

  12. Rauma Regional Hospital, Steniuksenkatu 2, 26100, Rauma, Finland

    Eero Jukka

  13. Rheumatism Foundation Hospital, Pikijärventie 1, 18120, Heinola, Finland

    Satu Nyrhinen

  14. COXA Hospital for Joint Replacement, Biokatu 6 B, 33520, Tampere, Finland

    Yrjö T. Konttinen

  15. Helsinki University Central Hospital, Haartmaninkatu 4, 00290, Helsinki, Finland

    Dan C. Nordström

Authors
  1. Liisa M. Virkki
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Heikki Valleala
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yuya Takakubo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jorma Vuotila
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Heikki Relas
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Riitta Komulainen
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Riitta Koivuniemi
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Urpo Yli-Kerttula
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Markku Mali
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Susanna Sihvonen
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Maija-Liisa Krogerus
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Eero Jukka
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Satu Nyrhinen
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Yrjö T. Konttinen
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Dan C. Nordström
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Dan C. Nordström.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Virkki, L.M., Valleala, H., Takakubo, Y. et al. Outcomes of switching anti-TNF drugs in rheumatoid arthritis—a study based on observational data from the Finnish Register of Biological Treatment (ROB-FIN). Clin Rheumatol 30, 1447–1454 (2011). https://doi.org/10.1007/s10067-011-1779-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10067-011-1779-1

Keywords

Search

Navigation