Advertisement

Rheumatology International

, Volume 30, Issue 12, pp 1611–1620 | Cite as

Infliximab treatment in patients with rheumatoid arthritis and spondyloarthropathies in one rheumatological center: two years’ drug survival

  • Tiina Levälampi
  • Markku Korpela
  • Katriina Vuolteenaho
  • Eeva MoilanenEmail author
Original Article
  • 157 Downloads

Abstract

The aim of the present study was to determine the drug survival during 2 years’ follow-up in patients (n = 104) with active rheumatoid arthritis (RA) or spondyloarthropathy (SpA) who were treated with infliximab as their first biological anti-rheumatic drug in a single rheumatological center. According to the national guidelines, infliximab was added to the treatment with combinations of traditional disease-modifying anti-rheumatic drugs (DMARD). Patients’ records were analyzed at baseline and after 2 years of follow-up. The response to treatment was determined inadequate if the response was lower than ACR50 (American College of Rheumatology 50) in RA or the reduction of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) was lower than 50% or 2 cm in SpA. Drug survival in infliximab-treated patients after 2 years was 40%, and among those who continued with the therapy the prednisolone dose has been reduced by 52%. Discontinuation rate was 60% during 2 years of follow-up, where 7% achieved remission and 22% of the patients were regarded as poor responders. As much as 24% of the patients discontinued due to an adverse event, mainly infections and hypersensitivity reactions. Two drug-related leukopenias were diagnosed. In the present study, infliximab therapy was initiated in RA or SpA patients who had active disease despite ongoing treatment with combinations of DMARDs. The drug survival with infliximab was 40% after 2 years of follow-up. During the 2-year follow-up, 60% discontinued infliximab treatment, mainly due to unsatisfactory or waning efficacy or a severe adverse event.

Keywords

Infliximab Rheumatoid arthritis Spondyloarthropathies Adverse events 

Notes

Acknowledgments

We thank Mrs. Heli Määttä and Mrs. Heli Pikkuharju for their excellent secretarial help. The study was supported by the Clinical Drug Research Graduate School, Finland and the Competitive Research Funding of the Pirkanmaa Hospital District.

References

  1. 1.
    Maini R, St Clair EW, Breedveld F, Furst D, Kalden J, Weisman M, Smolen J, Emery P, Harriman G, Feldmann M, Lipsky P (1999) Infliximab (chimeric anti-tumour necrosis factor alpha monoclonal antibody) versus placebo in rheumatoid arthritis patients receiving concomitant methotrexate: a randomised phase III trial. ATTRACT Study Group. Lancet 354:1932–1939CrossRefPubMedGoogle Scholar
  2. 2.
    Lipsky PE, van der Heijde DM, St Clair EW, Furst DE, Breedveld FC, Kalden JR, Smolen JS, Weisman M, Emery P, Feldmann M, Harriman GR, Maini RN, Anti-Tumor Necrosis Factor Trial in Rheumatoid Arthritis with Concomitant Therapy Study Group (2000) Infliximab and methotrexate in the treatment of rheumatoid arthritis. Anti-Tumor Necrosis Factor Trial in Rheumatoid Arthritis with Concomitant Therapy Study Group. N Engl J Med 343:1594–1602CrossRefPubMedGoogle Scholar
  3. 3.
    St Clair EW, van der Heijde DM, Smolen JS, Maini RN, Bathon JM, Emery P, Keystone E, Schiff M, Kalden JR, Wang B, Dewoody K, Weiss R, Baker D, Active-Controlled Study of Patients Receiving Infliximab for the Treatment of Rheumatoid Arthritis of Early Onset Study Group (2004) Combination of infliximab and methotrexate therapy for early rheumatoid arthritis: a randomized, controlled trial. Arthritis Rheum 50:3432–3443CrossRefPubMedGoogle Scholar
  4. 4.
    Goekoop-Ruiterman YP, de Vries-Bouwstra JK, Allaart CF, van Zeben D, Kerstens PJ, Hazes JM, Zwinderman AH, Ronday HK, Han KH, Westedt ML, Gerards AH, van Groenendael JH, Lems WF, van Krugten MV, Breedveld FC, Dijkmans BA (2005) Clinical and radiographic outcomes of four different treatment strategies in patients with early rheumatoid arthritis (the BeSt study): a randomized, controlled trial. Arthritis Rheum 52:3381–3390CrossRefPubMedGoogle Scholar
  5. 5.
    van der Heijde D, Dijkmans B, Geusens P, Sieper J, DeWoody K, Williamson P, Braun J, Ankylosing Spondylitis Study for the Evaluation of Recombinant Infliximab Therapy Study Group (2005) Efficacy and safety of infliximab in patients with ankylosing spondylitis: results of a randomized, placebo-controlled trial (ASSERT). Arthritis Rheum 52:582–591CrossRefPubMedGoogle Scholar
  6. 6.
    Braun J, Deodhar A, Dijkmans B, Geusens P, Sieper J, Williamson P, Xu W, Visvanathan S, Baker D, Goldstein N, van der Heijde D, Ankylosing Spondylitis Study for the Evaluation of Recombinant Infliximab Therapy Study Group (2008) Efficacy and safety of infliximab in patients with ankylosing spondylitis over a two-year period. Arthritis Rheum 59:1270–1278CrossRefPubMedGoogle Scholar
  7. 7.
    Braun J, Baraliakos X, Brandt J, Sieper J (2005) Therapy of ankylosing spondylitis. Part II. Biological therapies in the spondyloarthritides. Scand J Rheumatol 34:178–190CrossRefPubMedGoogle Scholar
  8. 8.
    Flendrie M, Creemers MC, Welsing PM, den Broeder AA, van Riel PL (2003) Survival during treatment with tumour necrosis factor blocking agents in rheumatoid arthritis. Ann Rheum Dis 62(Suppl 2):ii30–ii33PubMedGoogle Scholar
  9. 9.
    Wendling D, Materne GE, Michel F, Lohse A, Lehuede G, Toussirot E, Massol J, Woronoff-Lemsi MC (2005) Infliximab continuation rates in patients with rheumatoid arthritis in everyday practice. Joint Bone Spine 72:309–312CrossRefPubMedGoogle Scholar
  10. 10.
    Voulgari PV, Alamanos Y, Nikas SN, Bougias DV, Temekonidis TI, Drosos AA (2005) Infliximab therapy in established rheumatoid arthritis: an observational study. Am J Med 118:515–520CrossRefPubMedGoogle Scholar
  11. 11.
    Listing J, Strangfeld A, Kary S, Rau R, von Hinueber U, Stoyanova-Scholz M, Gromnica-Ihle E, Antoni C, Herzer P, Kekow J, Schneider M, Zink A (2005) Infections in patients with rheumatoid arthritis treated with biologic agents. Arthritis Rheum 52:3403–3412CrossRefPubMedGoogle Scholar
  12. 12.
    Dixon WG, Watson K, Lunt M, Hyrich KL, Silman AJ, Symmons DP, British Society for Rheumatology Biologics Register (2006) Rates of serious infection, including site-specific and bacterial intracellular infection, in rheumatoid arthritis patients receiving anti-tumor necrosis factor therapy: results from the British Society for Rheumatology Biologics Register. Arthritis Rheum 54:2368–2376CrossRefPubMedGoogle Scholar
  13. 13.
    Salliot C, Gossec L, Ruyssen-Witrand A, Luc M, Duclos M, Guignard S, Dougados M (2007) Infections during tumour necrosis factor-{alpha} blocker therapy for rheumatic diseases in daily practice: a systematic retrospective study of 709 patients. Rheumatology (Oxford) 46:327–334CrossRefGoogle Scholar
  14. 14.
    Buch MH, Bingham SJ, Bryer D, Emery P (2007) Long-term infliximab treatment in rheumatoid arthritis: subsequent outcome of initial responders. Rheumatology (Oxford) 46:1153–1156CrossRefGoogle Scholar
  15. 15.
    Wasserman MJ, Weber DA, Guthrie JA, Bykerk VP, Lee P, Keystone EC (2004) Infusion-related reactions to infliximab in patients with rheumatoid arthritis in a clinical practice setting: relationship to dose, antihistamine pretreatment, and infusion number. J Rheumatol 31:1912–1917PubMedGoogle Scholar
  16. 16.
    Figueiredo IT, Morel J, Sany J, Combe B (2008) Maintenance and tolerability of infliximab in a cohort of 152 patients with rheumatoid arthritis. Clin Exp Rheumatol 26:18–23PubMedGoogle Scholar
  17. 17.
    Working group set up by Finnish Medical Society Duodecim and Finnish Society for Rheumatology, Helsinki, Finland. (Updated 18 Sep 2009) Rheumatoid arthritis Current Care Guideline. Finnish Medical Society Duodecim. http://www.kaypahoito.fi (in Finnish). Accessed at 06 Oct 2009
  18. 18.
    Levälampi T, Korpela M, Vuolteenaho K, Moilanen E (2008) Infliximab treatment in patients with rheumatoid arthritis and spondyloarthropathies in clinical practice: adverse events and other reasons for discontinuation of treatment. Scand J Rheumatol 37:6–12CrossRefPubMedGoogle Scholar
  19. 19.
    Felson DT, Anderson JJ, Boers M, Bombardier C, Furst D, Goldsmith C, Katz LM, Lightfoot R Jr, Paulus H, Strand V (1995) American College of Rheumatology. Preliminary definition of improvement in rheumatoid arthritis. Arthritis Rheum 38:727–735CrossRefPubMedGoogle Scholar
  20. 20.
    Möttönen T, Hannonen P, Leirisalo-Repo M, Nissilä M, Kautiainen H, Korpela M, Laasonen L, Julkunen H, Luukkainen R, Vuori K, Paimela L, Blåfield H, Hakala M, Ilva K, Yli-Kerttula U, Puolakka K, Jarvinen P, Hakola M, Piirainen H, Ahonen J, Palvimaki I, Forsberg S, Koota K, Friman C (1999) Comparison of combination therapy with single-drug therapy in early rheumatoid arthritis: a randomised trial. FIN-RACo trial group. Lancet 353:1568–1573CrossRefPubMedGoogle Scholar
  21. 21.
    Mäkinen H, Kautiainen H, Hannonen P, Möttönen T, Leirisalo-Repo M, Laasonen L, Korpela M, Blåfield H, Hakola M, Sokka T (2007) Sustained remission and reduced radiographic progression with combination disease-modifying antirheumatic drugs in early rheumatoid arthritis. J Rheumatol 34:316–321PubMedGoogle Scholar
  22. 22.
    Feltelius N, Fored CM, Blomqvist P, Bertilsson L, Geborek P, Jacobsson LT, Lindblad S, Lysholm J, Rantapaa-Dahlqvist S, Saxne T, Klareskog L, ARTIS Group (2005) Results from a nationwide postmarketing cohort study of patients in Sweden treated with etanercept. Ann Rheum Dis 64:246–252CrossRefPubMedGoogle Scholar
  23. 23.
    Brocq O, Roux CH, Albert C, Breuil V, Aknouche N, Ruitord S, Mousnier A, Euller-Ziegler L (2007) TNFalpha antagonist continuation rates in 442 patients with inflammatory joint disease. Joint Bone Spine 74:148–154CrossRefPubMedGoogle Scholar
  24. 24.
    Mancarella L, Bobbio-Pallavicini F, Ceccarelli F, Falappone PC, Ferrante A, Malesci D, Massara A, Nacci F, Secchi ME, Manganelli S, Salaffi F, Bambara ML, Bombardieri S, Cutolo M, Ferri C, Galeazzi M, Gerli R, Giacomelli R, Grassi W, Lapadula G, Cerinic MM, Montecucco C, Trotta F, Triolo G, Valentini G, Valesini G, Ferraccioli GF, GISEA group (2007) Good clinical response, remission, and predictors of remission in rheumatoid arthritis patients treated with tumor necrosis factor-alpha blockers: the GISEA study. J Rheumatol 34:1670–1673PubMedGoogle Scholar
  25. 25.
    Kristensen LE, Saxne T, Nilsson JA, Geborek P (2006) Impact of concomitant DMARD therapy on adherence to treatment with etanercept and infliximab in rheumatoid arthritis. Results from a six-year observational study in southern Sweden. Arthritis Res Ther 8:R174CrossRefPubMedGoogle Scholar
  26. 26.
    Levälampi T, Korpela M, Vuolteenaho K, Moilanen E (2008) Etanercept and adalimumab treatment in patients with rheumatoid arthritis and spondyloarthropathies in clinical practice: adverse events and other reasons leading to discontinuation of the treatment. Rheumatol Int 28:261–269CrossRefPubMedGoogle Scholar
  27. 27.
    Carmona L, Gomez-Reino JJ, BIOBADASER Group (2006) Survival of TNF antagonists in spondylarthritis is better than in rheumatoid arthritis. Data from the Spanish registry BIOBADASER. Arthritis Res Ther 8:R72CrossRefPubMedGoogle Scholar
  28. 28.
    Heiberg MS, Koldingsnes W, Mikkelsen K, Rodevand E, Kaufmann C, Mowinckel P, Kvien TK (2008) The comparative one-year performance of anti-tumor necrosis factor alpha drugs in patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis: results from a longitudinal, observational, multicenter study. Arthritis Rheum 59:234–240CrossRefPubMedGoogle Scholar
  29. 29.
    van Vollenhoven RF, Klareskog L (2007) Infliximab dosage and infusion frequency in clinical practice: experiences in the Stockholm Biologics Registry STURE. Scand J Rheumatol 36:418–423CrossRefPubMedGoogle Scholar
  30. 30.
    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 54:711–715CrossRefPubMedGoogle Scholar
  31. 31.
    Xu Z, Seitz K, Fasanmade A, Ford J, Williamson P, Xu W, Davis HM, Zhou H (2008) Population pharmacokinetics of infliximab in patients with ankylosing spondylitis. J Clin Pharmacol 48:681–695CrossRefPubMedGoogle Scholar
  32. 32.
    St Clair EW, Wagner CL, Fasanmade AA, Wang B, Schaible T, Kavanaugh A, Keystone EC (2002) The relationship of serum infliximab concentrations to clinical improvement in rheumatoid arthritis: results from ATTRACT, a multicenter, randomized, double-blind, placebo-controlled trial. Arthritis Rheum 46:1451–1459CrossRefPubMedGoogle Scholar
  33. 33.
    Mutru O, Laakso M, Isomäki H, Koota K (1985) Ten-year mortality and causes of death in patients with rheumatoid arthritis. Br Med J (Clin Res Ed) 290:1797–1799CrossRefGoogle Scholar
  34. 34.
    Doran MF, Crowson CS, Pond GR, O’Fallon WM, Gabriel SE (2002) Predictors of infection in rheumatoid arthritis. Arthritis Rheum 46:2294–2300CrossRefPubMedGoogle Scholar
  35. 35.
    Smitten AL, Choi HK, Hochberg MC, Suissa S, Simon TA, Testa MA, Chan KA (2008) The risk of hospitalized infection in patients with rheumatoid arthritis. J Rheumatol 35:387–393PubMedGoogle Scholar
  36. 36.
    Caporali R, Caprioli M, Bobbio-Pallavicini F, Montecucco C (2008) DMARDS and infections in rheumatoid arthritis. Autoimmun Rev 8:139–143CrossRefPubMedGoogle Scholar
  37. 37.
    Bernatsky S, Hudson M, Suissa S (2007) Anti-rheumatic drug use and risk of serious infections in rheumatoid arthritis. Rheumatology (Oxford) 46:1157–1160CrossRefGoogle Scholar
  38. 38.
    Lacaille D, Guh DP, Abrahamowicz M, Anis AH, Esdaile JM (2008) Use of nonbiologic disease-modifying antirheumatic drugs and risk of infection in patients with rheumatoid arthritis. Arthritis Rheum 59:1074–1081CrossRefPubMedGoogle Scholar
  39. 39.
    Curtis JR, Patkar N, Xie A, Martin C, Allison JJ, Saag M, Shatin D, Saag KG (2007) Risk of serious bacterial infections among rheumatoid arthritis patients exposed to tumor necrosis factor alpha antagonists. Arthritis Rheum 56:1125–1133CrossRefPubMedGoogle Scholar
  40. 40.
    Favalli EG, Desiati F, Atzeni F, Sarzi-Puttini P, Caporali R, Pallavicini FB, Gorla R, Filippini M, Marchesoni A (2009) Serious infections during anti-TNFalpha treatment in rheumatoid arthritis patients. Autoimmun Rev 8:266–273CrossRefPubMedGoogle Scholar
  41. 41.
    Augustsson J, Eksborg S, Ernestam S, Gullstrom E, van Vollenhoven R (2007) Low-dose glucocorticoid therapy decreases risk for treatment-limiting infusion reaction to infliximab in patients with rheumatoid arthritis. Ann Rheum Dis 66:1462–1466CrossRefPubMedGoogle Scholar
  42. 42.
    Vidal F, Fontova R, Richart C (2003) Severe neutropenia and thrombocytopenia associated with infliximab. Ann Intern Med 139:W–W63PubMedGoogle Scholar
  43. 43.
    Favalli EG, Varenna M, Sinigaglia L (2005) Drug-induced agranulocytosis during treatment with infliximab in enteropathic spondyloarthropathy. Clin Exp Rheumatol 23:247–250PubMedGoogle Scholar
  44. 44.
    Montane E, Salles M, Barriocanal A, Riera E, Costa J, Tena X (2007) Antitumor necrosis factor-induced neutropenia: a case report with double-positive rechallenges. Clin Rheumatol 26:1527–1529CrossRefPubMedGoogle Scholar
  45. 45.
    Konttinen L, Honkanen V, Uotila T, Pöllänen J, Waahtera M, Romu M, Puolakka K, Vasala M, Karjalainen A, Luukkainen R, Nordström DC, for the ROB-FIN study group (2006) Biological treatment in rheumatic diseases: results from a longitudinal surveillance: adverse events. Rheumatol Int 26:916–922CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Tiina Levälampi
    • 1
  • Markku Korpela
    • 2
  • Katriina Vuolteenaho
    • 1
  • Eeva Moilanen
    • 1
    Email author
  1. 1.The Immunopharmacology Research Group, Medical School, University of Tampere and Research UnitTampere University HospitalTampereFinland
  2. 2.Deparment of Internal Medicine, Center for Rheumatic DiseasesTampere University HospitalTampereFinland

Personalised recommendations