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Extended report
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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