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Effectiveness and safety of a second and third biological agent after failing etanercept in juvenile idiopathic arthritis: results from the Dutch National ABC Register
  1. Marieke H Otten1,
  2. Femke H M Prince1,
  3. Janneke Anink1,
  4. Rebecca ten Cate2,
  5. Esther P A H Hoppenreijs3,
  6. Wineke Armbrust4,
  7. Yvonne Koopman-Keemink5,
  8. Philomine A van Pelt1,
  9. Sylvia Kamphuis1,
  10. Simone L Gorter6,
  11. Koert M Dolman7,
  12. Joost F Swart8,
  13. J Merlijn van den Berg9,
  14. Nico M Wulffraat8,
  15. Marion A J van Rossum9,
  16. Lisette W A van Suijlekom-Smit1
  1. 1Department of Paediatrics/Paediatric Rheumatology, Erasmus MC Sophia Children's Hospital, Rotterdam, The Netherlands
  2. 2Department of Paediatrics/Paediatric Rheumatology, Leiden University Medical Centre, Leiden, The Netherlands
  3. 3Department of Paediatrics/Paediatric Rheumatology, St Maartenskliniek and Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
  4. 4Department of Paediatrics/Paediatric Rheumatology, Beatrix Children's Hospital, University Medical Centre Groningen, Groningen, The Netherlands
  5. 5Department of Paediatrics, Hagaziekenhuis Juliana Children's Hospital, The Hague, The Netherlands
  6. 6Department of Internal Medicine, Subdivision Rheumatology, Maastricht University Medical Center, Maastricht, The Netherlands
  7. 7Department of Paediatrics/Paediatric Rheumatology, St Lucas Andreas Hospital and Reade Institute, Amsterdam, The Netherlands
  8. 8Department of Paediatrics/Paediatric Rheumatology, Utrecht MC Wilhelmina Children's Hospital, Utrecht, The Netherlands
  9. 9Department of Paediatrics/Paediatric Rheumatology, Emma Children's Hospital/Academic Medical Centre and Reade Institute, Amsterdam, The Netherlands
  1. Correspondence to Dr Marieke H Otten, Department of Paediatrics, Sp 1546, Erasmus MC Sophia Children's Hospital, PO Box 2060, Rotterdam 3000 CB, The Netherlands; m.otten{at}


Objective To evaluate the effectiveness and safety of switching to a second or third biological agent in juvenile idiopathic arthritis (JIA) after etanercept failure.

Methods The Arthritis and Biologicals in Children Register aims to include all Dutch JIA patients who have used biological agents. Data on the disease course were used to estimate drug survival with Kaplan–Meier and calculate adverse event (AE) rates.

Results Of 307 biologically naive JIA patients who started etanercept, 80 (26%) switched to a second and 22 (7%) to a third biological agent. During 1030 patient-years of follow-up after the introduction of etanercept, 49 switches to adalimumab, 28 infliximab, 17 anakinra, four abatacept and four trial drugs were evaluated. 84% (95% CI 80% to 88%) of patients who started etanercept as a first biological agent were, after 12 months, still on the drug, compared with 47% (95% CI 35% to 60%) who started a second and 51% (95% CI 26% to 76%) who started a third biological agent. Patients who switched because of primary ineffectiveness continued the second agent less often (32%, 95% CI 12% to 53%). After etanercept failure, drug continuation of adalimumab was similar to infliximab for patients with non-systemic JIA; anakinra was superior to a second TNF-blocker for systemic JIA. AE rates within first 12 months after initiation were comparable for each course and each biological agent.

Conclusions Switching to another biological agent is common, especially for systemic JIA patients. A second (and third) agent was less effective than the first. The choice of second biological agent by the physician mainly depends on availability and JIA category.

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  • Funding The Dutch Board of Health Insurances (from 2003 to 2006), Pfizer BV (formerly Wyeth International BV, since 2007) and Abbott BV (since 2010). Support was unconditional, and there was no role in study planning, design, management, data analyses, interpretation of the data, and preparation or approval of the manuscript.

  • Competing interests All authors have completed and submitted the ICMJE form for disclosure of potential conflicts of interest. MHO received outside the submitted work travel grants from Pfizer (formerly Wyeth), and support for consultancy from Roche. FHMP: no financial disclosures with regard to the submitted work, outside the submitted work she received consultancy fees from Roche, travel grants from Pfizer (formerly Wyeth), and grants for thesis from Abbott, Bristol-Myers Squibb, Novartis, Tevapharma and Pfizer (formerly Wyeth). LWAvSS: received grants for the submitted work from the Dutch Board of Health Insurances, Pfizer (formerly Wyeth) and Abbott, received consulting fees and support for travel to meetings from Pfizer (formerly Wyeth). Outside the submitted work she received consultancy fees from Roche and Novartis, grants from the Dutch Arthritis Association and travel expenses from Bristol-Myers Squibb. RtC: received outside the submitted work grants, support for travel, and consultancy from Pfizer (formerly Wyeth). NMW: received outside the submitted work payment for lectures from Novartis. JA, WA, KMD, SLG, EPAHH, SK, YKK, JFS, JMvB, PAvP and MAJvR: no financial disclosures reported.

  • Ethics approval The study protocol was approved by the Medical Ethics Committee at Erasmus MC Rotterdam and by all participating hospitals.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement Additional unpublished data are not available for persons not involved in the Dutch Arthritis and Biologicals in Children Working Group.

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