Skip to main content

Advertisement

SpringerLink
Log in

Real-life 10-year retention rate of first-line anti-TNF drugs for inflammatory arthritides in adult- and juvenile-onset populations: similarities and differences

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

Abstract

The aim of this study is to retrospectively analyze 10-year drug survival of first-line TNF inhibitor (TNFi) in rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis (PsA), and juvenile idiopathic arthritis (JIA) patients, comparing withdrawal rates and discontinuation pattern between adult- and juvenile-onset populations. RA, AS, PsA, and JIA patients treated with infliximab, etanercept, or adalimumab as first TNFi between 1999 and 2015 were extracted from a local registry. Drug survival up to 10-year follow-up was evaluated by the Kaplan-Meier method and compared according to age (adult vs juvenile onset), TNFi agent, and discontinuation reason by a stratified log-rank test. Three hundred sixty JIA (205 etanercept, 66 adalimumab, and 89 infliximab) and 951 (607 RA, 188 AS, and 156 PsA) adult patients (464 infliximab, 262 adalimumab, and 225 etanercept) were included. After exclusion of systemic-onset JIA (18.5%), overall 10-year retention rate was 31.8%, with no difference between adult- and juvenile-onset patients (32.1 and 30.2%, respectively; HR 0.938 [95% CI 0.782–1.125]). Etanercept showed the highest drug survival in adult-onset population (p < 0.0001 vs both monoclonal antibodies) and infliximab the lowest in juvenile-onset population (p = 0.005 vs adalimumab and p < 0.0001 vs etanercept). Inefficacy was the most frequent reason for TNFi withdrawal in adult population (29.75%) with a significantly higher risk of discontinuation than in juvenile-onset subgroup (HR 1.390 [95% CI 1.060–1.824]). Serious infections and malignancies caused TNFi withdrawal only in adult whereas gastrointestinal, neuropsychiatric, and ocular complications quite only in juvenile patients. Despite a similar 10-year drug survival, adult- and juvenile-onset subpopulations showed a significantly different pattern of TNFi reasons for discontinuation.

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
Fig. 3

Similar content being viewed by others

References

  1. Petty RE, Southwood TR, Manners P et al (2004) International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001. J Rheumatol 31:390–392

    PubMed  Google Scholar 

  2. Ruperto N, Lovell DJ, Cuttica R et al (2010) Long-term efficacy and safety of infliximab plus methotrexate for the treatment of polyarticular-course juvenile rheumatoid arthritis: findings from an open-label treatment extension. Ann Rheum dis 69:718–722

    Article  CAS  PubMed  Google Scholar 

  3. Gerloni V, Pontikaki I, Gattinara M et al (2005) Efficacy of repeated intravenous infusions of an anti-tumor necrosis factor alpha monoclonal antibody, infliximab, in persistently active, refractory juvenile idiopathic arthritis: results of an open-label prospective study. Arthritis Rheum 52:548–553

    Article  CAS  PubMed  Google Scholar 

  4. Marchesoni A, Zaccara E, Gorla R et al (2009) TNF-alpha antagonist survival rate in a cohort of rheumatoid arthritis patients observed under conditions of standard clinical practice. Ann N Y Acad Sci 1173:837–846

    Article  CAS  PubMed  Google Scholar 

  5. Glintborg B, Østergaard M, Dreyer L et al (2011) Treatment response, drug survival, and predictors thereof in 764 patients with psoriatic arthritis treated with anti-tumor necrosis factor α therapy: results from the nationwide Danish DANBIO registry. Arthritis Rheum 63:382–390

    Article  PubMed  Google Scholar 

  6. Glintborg B, Østergaard M, Krogh NS et al (2010) Predictors of treatment response and drug continuation in 842 patients with ankylosing spondylitis treated with anti-tumour necrosis factor: results from 8 years’ surveillance in the Danish nationwide DANBIO registry. Ann Rheum dis 69:2002–2008

    Article  CAS  PubMed  Google Scholar 

  7. Lie E, Kristensen LE, Forsblad-d’Elia H et al (2015) The effect of comedication with conventional synthetic disease modifying antirheumatic drugs on TNF inhibitor drug survival in patients with ankylosing spondylitis and undifferentiated spondyloarthritis: results from a nationwide prospective study. Ann Rheum dis 74:970–978

    Article  CAS  PubMed  Google Scholar 

  8. Fagerli KM, Lie E, van der Heijde DM et al (2014) The role of methotrexate co-medication in TNF-inhibitor treatment in patients with psoriatic arthritis: results from 440 patients included in the NOR-DMARD study. Ann Rheum dis 73:132–137

    Article  CAS  PubMed  Google Scholar 

  9. Favalli EG, Pregnolato F, Biggioggero M et al (2016) Twelve-year retention rate of first-line tumor necrosis factor inhibitors in rheumatoid arthritis: real-life data from a local registry. Arthritis Care & Research 68:432–439

    Article  CAS  Google Scholar 

  10. Tynjala P, Vahasalo P, Honkanen V et al (2009) Drug survival of the first and second course of anti-tumour necrosis factor agents in juvenile idiopathic arthritis. Ann Rheum dis 68:552–557

    Article  CAS  PubMed  Google Scholar 

  11. Mourão AF, Santos MJ, Melo Gomes JA et al (2016) Effectiveness and long-term retention of anti-tumour necrosis factor treatment in juvenile and adult patients with juvenile idiopathic arthritis: data from Reuma.pt. Rheumatology (Oxford) 55:697–703

    Article  Google Scholar 

  12. Arnett FC, Edworthy SM, Bloch DA et al (1988) The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 31:315–324

    Article  CAS  PubMed  Google Scholar 

  13. Linden SVD, Valkenburg HA, Cats A (1984) Evaluation of diagnostic criteria for ankylosing spondylitis. Arthritis Rheum 27:361–368

    Article  PubMed  Google Scholar 

  14. Moll JM, Wright V (1973) Psoriatic arthritis. Semin Arthritis Rheum 3:55–78

    Article  CAS  PubMed  Google Scholar 

  15. Lin Y-T, Wang C-T, Gershwin ME et al (2011) The pathogenesis of oligoarticular/polyarticular vs systemic juvenile idiopathic arthritis. Autoimmun rev 10:482–489

    Article  CAS  PubMed  Google Scholar 

  16. Vastert SJ, Kuis W, Grom AA (2009) Systemic JIA: new developments in the understanding of the pathophysiology and therapy. Best Pract res Clin Rheumatol 23:655–664

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Favalli EG, Selmi C, Becciolini A, et al. Eight-year retention rate of first-line tumor necrosis factor inhibitors in spondyloarthritis: a multi-center retrospective analysis. Arthritis Care Res 2016; Accepted Author Manuscript. doi:10.1002/acr.23090

  18. Soliman MM, Ashcroft DM, Watson KD et al (2011) Impact of concomitant use of DMARDs on the persistence with anti-TNF therapies in patients with rheumatoid arthritis: results from the British Society for Rheumatology Biologics Register. Ann Rheum dis 70:583–589

    Article  PubMed  PubMed Central  Google Scholar 

  19. 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:R72

    Article  PubMed  PubMed Central  Google Scholar 

  20. Pan Du SM, Dehler S, Ciurea A et al (2009) Comparison of drug retention rates and causes of drug discontinuation between anti-tumor necrosis factor agents in rheumatoid arthritis. Arthritis Rheum 61:560–568

    Article  Google Scholar 

  21. Kievit W, Fransen J, Adang EMM et al (2011) Long-term effectiveness and safety of TNF-blocking agents in daily clinical practice: results from the Dutch Rheumatoid Arthritis Monitoring register. Rheumatology (Oxford) 50:196–203

    Article  CAS  Google Scholar 

  22. Rosenblat JD, Cha DS, Mansur RB et al (2014) Inflamed moods: a review of the interactions between inflammation and mood disorders. Prog Neuro-Psychopharmacol Biol Psychiatry 53:23–34

    Article  CAS  Google Scholar 

  23. Gerloni V, Pontikaki I, Gattinara M et al (2008) Focus on adverse events of tumour necrosis factor alpha blockade in juvenile idiopathic arthritis in an open monocentric long-term prospective study of 163 patients. Ann Rheum dis 67:1145–1152

    Article  CAS  PubMed  Google Scholar 

  24. Sen ES, Dick AD, Ramanan AV (2015) Uveitis associated with juvenile idiopathic arthritis. Nat rev Rheumatol 11:338–348

    Article  CAS  PubMed  Google Scholar 

  25. Barthel D, Ganser G, Kuester R-M et al (2015) Inflammatory bowel disease in juvenile idiopathic arthritis patients treated with biologics. J Rheumatol 42:2160–2165

    Article  CAS  PubMed  Google Scholar 

  26. Stolwijk C, van Tubergen A, Castillo-Ortiz JD et al (2015) Prevalence of extra-articular manifestations in patients with ankylosing spondylitis: a systematic review and meta-analysis. Ann Rheum dis 74:65–73

    Article  PubMed  Google Scholar 

  27. Tappeiner C, Schenck S, Niewerth M et al (2016) Impact of antiinflammatory treatment on the onset of uveitis in juvenile idiopathic arthritis: longitudinal analysis from a nationwide pediatric rheumatology database. Arthritis Care & Research 68:46–54

    Article  CAS  Google Scholar 

  28. Wu D, Guo Y-Y, Xu N-N et al (2015) Efficacy of anti-tumor necrosis factor therapy for extra-articular manifestations in patients with ankylosing spondylitis: a meta-analysis. BMC Musculoskelet Disord 16:19

    Article  PubMed  PubMed Central  Google Scholar 

  29. Simonini G, Druce K, Cimaz R et al (2014) Current evidence of anti-tumor necrosis factor α treatment efficacy in childhood chronic uveitis: a systematic review and meta-analysis approach of individual drugs. Arthritis Care & Research 66:1073–1084

    Article  CAS  Google Scholar 

  30. Braun J, Baraliakos X, Listing J et al (2005) Decreased incidence of anterior uveitis in patients with ankylosing spondylitis treated with the anti-tumor necrosis factor agents infliximab and etanercept. Arthritis Rheum 52:2447–2451

    Article  CAS  PubMed  Google Scholar 

  31. Sandborn WJ (2003) Optimizing anti-tumor necrosis factor strategies in inflammatory bowel disease. Curr Gastroenterol rep 5:501–505

    Article  PubMed  Google Scholar 

  32. Braun J, Baraliakos X, Listing J et al (2007) Differences in the incidence of flares or new onset of inflammatory bowel diseases in patients with ankylosing spondylitis exposed to therapy with anti-tumor necrosis factor alpha agents. Arthritis Rheum 57:639–647

    Article  CAS  PubMed  Google Scholar 

  33. Beukelman T, Xie F, Chen L et al (2012) Rates of hospitalized bacterial infection associated with juvenile idiopathic arthritis and its treatment. Arthritis Rheum 64:2773–2780

    Article  PubMed  PubMed Central  Google Scholar 

  34. Doran MF, Crowson CS, Pond GR et al (2002) Frequency of infection in patients with rheumatoid arthritis compared with controls: a population-based study. Arthritis Rheum 46:2287–2293

    Article  PubMed  Google Scholar 

  35. Listing J, Strangfeld A, Kary S et al (2005) Infections in patients with rheumatoid arthritis treated with biologic agents. Arthritis Rheum 52:3403–3412

    Article  CAS  PubMed  Google Scholar 

  36. Greenberg JD, Reed G, Kremer JM et al (2010) Association of methotrexate and tumour necrosis factor antagonists with risk of infectious outcomes including opportunistic infections in the CORRONA registry. Ann Rheum dis 69:380–386

    Article  CAS  PubMed  Google Scholar 

  37. Galloway JB, Hyrich KL, Mercer LK et al (2011) Anti-TNF therapy is associated with an increased risk of serious infections in patients with rheumatoid arthritis especially in the first 6 months of treatment: updated results from the British Society for Rheumatology Biologics Register with special emphasis on risks in the elderly. Rheumatology (Oxford) 50:124–131

    Article  CAS  Google Scholar 

  38. Becker I, Horneff G. Risk of serious infection in juvenile idiopathic arthritis patients associated with TNF-inhibitors and disease activity in the German BIKER registry. Arthritis care & research Published Online First: 7 July 2016.

  39. Baecklund E, Iliadou A, Askling J et al (2006) Association of chronic inflammation, not its treatment, with increased lymphoma risk in rheumatoid arthritis. Arthritis Rheum 54:692–701

    Article  PubMed  Google Scholar 

  40. Nordstrom BL, Mines D, Gu Y et al (2012) Risk of malignancy in children with juvenile idiopathic arthritis not treated with biologic agents. Arthritis Care & Research 64:1357–1364

    Article  Google Scholar 

  41. Hellgren K, Smedby KE, Backlin C et al (2014) Ankylosing spondylitis, psoriatic arthritis, and risk of malignant lymphoma: a cohort study based on nationwide prospectively recorded data from Sweden. Arthritis Rheumatol 66:1282–1290

    Article  CAS  PubMed  Google Scholar 

  42. Onel KB, Onel K (2012) Tumor necrosis factor inhibitors and cancer in juvenile idiopathic arthritis: disentangling the web. Arthritis Rheum 64:966–969

    Article  PubMed  Google Scholar 

  43. Bongartz T, Sutton AJ, Sweeting MJ et al (2006) Anti-TNF antibody therapy in rheumatoid arthritis and the risk of serious infections and malignancies: systematic review and meta-analysis of rare harmful effects in randomized controlled trials. Jama 295:2275–2285

    Article  CAS  PubMed  Google Scholar 

  44. Strangfeld A, Hierse F, Rau R et al (2010) Risk of incident or recurrent malignancies among patients with rheumatoid arthritis exposed to biologic therapy in the German biologics register RABBIT. Arthritis res Ther 12:R5

    Article  PubMed  PubMed Central  Google Scholar 

  45. Mercer LK, Lunt M, Low ALS, Dixon WG, Watson KD, Symmons DPM et al (2015) Risk of solid cancer in patients exposed to anti-tumour necrosis factor therapy: results from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis. Ann Rheum dis 74(6):1087–1093

    Article  CAS  PubMed  Google Scholar 

  46. Beukelman T, Haynes K, Curtis JR et al (2012) Rates of malignancy associated with juvenile idiopathic arthritis and its treatment. Arthritis Rheum 64:1263–1271

    Article  PubMed  PubMed Central  Google Scholar 

  47. Tanaka Y, Hirata S, Saleem B, Emery P (2013) Discontinuation of biologics in patients with rheumatoid arthritis. Clin Exp Rheumatol 31(4 Suppl 78):S22–S27

    PubMed  Google Scholar 

  48. Chang CY, Meyer RML, Reiff AO (2015) Impact of medication withdrawal method on flare-free survival in patients with juvenile idiopathic arthritis on combination therapy. Arthritis Care res 67(5):658–666

    Article  CAS  Google Scholar 

  49. Hetland ML, Christensen IJ, Tarp U et al (2010) Direct comparison of treatment responses, remission rates, and drug adherence in patients with rheumatoid arthritis treated with adalimumab, etanercept, or infliximab: results from eight years of surveillance of clinical practice in the nationwide Danish DANBIO registry. Arthritis Rheum 62:22–32

    Article  CAS  PubMed  Google Scholar 

  50. Iannone F, Gremese E, Atzeni F et al (2012) Longterm retention of tumor necrosis factor-α inhibitor therapy in a large italian cohort of patients with rheumatoid arthritis from the GISEA registry: an appraisal of predictors. J Rheumatol 39:1179–1184. doi:10.3899/jrheum.111125

    Article  CAS  PubMed  Google Scholar 

  51. Schaeverbeke T, Truchetet M-E, Kostine M, Barnetche T, Bannwarth B, Richez C (2016) Immunogenicity of biologic agents in rheumatoid arthritis patients: lessons for clinical practice. Rheumatology (Oxford) 55(2):210–220

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Rheumatology, Gaetano Pini Institute, Via Gaetano Pini, 9, 20122, Milan, Italy

    Ennio Giulio Favalli, Irene Pontikaki, Andrea Becciolini, Maurizio Gattinara, Valeria Gerloni & Antonio Marchesoni

  2. Department of Clinical Sciences and Community Health, Division of Rheumatology, Gaetano Pini Institute, University of Milan, Milan, Italy

    Martina Biggioggero, Nicola Ughi, Micol Romano & Chiara Crotti

  3. Department of Clinical Sciences and Community Health, University of Milan and IRCCS Istituto Auxologico Italiano, Milan, Italy

    Pier Luigi Meroni

Authors
  1. Ennio Giulio Favalli
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Irene Pontikaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Andrea Becciolini
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Martina Biggioggero
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Nicola Ughi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Micol Romano
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Chiara Crotti
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Maurizio Gattinara
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Valeria Gerloni
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Antonio Marchesoni
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Pier Luigi Meroni
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ennio Giulio Favalli.

Ethics declarations

Disclosure statement

EGF, AM, and PLM have received lecture fees from BMS, Roche, MSD, UCB, Pfizer, and Abbvie. IP, MB, CC, AB, and MR have declared no conflicts of interest.

Funding statement

No specific funding was received from any funding bodies in the public, commercial, or not-for-profit sectors to carry out the work described in this manuscript.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Favalli, E.G., Pontikaki, I., Becciolini, A. et al. Real-life 10-year retention rate of first-line anti-TNF drugs for inflammatory arthritides in adult- and juvenile-onset populations: similarities and differences. Clin Rheumatol 36, 1747–1755 (2017). https://doi.org/10.1007/s10067-017-3712-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10067-017-3712-8

Keywords

Search

Navigation