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Treat to target (drug-free) inactive disease in DMARD-naive juvenile idiopathic arthritis: 24-month clinical outcomes of a three-armed randomised trial
  1. Petra Hissink Muller1,2,
  2. Danielle M C Brinkman1,3,
  3. Dieneke Schonenberg-Meinema4,
  4. Wytse Bastiaan van den Bosch1,
  5. Yvonne Koopman-Keemink5,
  6. Isabel C J Brederije1,
  7. Peter W Bekkering6,
  8. Taco W Kuijpers4,
  9. Marion Van Rossum7,8,
  10. Lisette WA van Suijlekom-Smit2,
  11. J Merlijn van den Berg4,
  12. Stefan Boehringer9,
  13. Cornelia F Allaart10,
  14. R ten Cate1
  1. 1 Department of Paediatric Rheumatology, Leiden University Medical Center, Leiden, The Netherlands
  2. 2 Department of Paediatric Rheumatology, Erasmus MC Sophia Children's Hospital, Rotterdam, The Netherlands
  3. 3 Department of Paediatrics, Alrijne Hospital Leiderdorp, Leiderdorp, The Netherlands
  4. 4 Department of Paediatric Hematology, Immunology, Rheumatology and Infectious Diseases, Emma Children’s Hospital AMC, University of Amsterdam, Amsterdam, The Netherlands
  5. 5 Department of Paediatrics, Hagaziekenhuis Juliana Children’s Hospital, The Hague, The Netherlands
  6. 6 Princess Máxima Center, Center for Pediatric Oncology, Utrecht, The Netherlands
  7. 7 Department of Paediatric Rheumatology, Amsterdam Rheumatology, Immunology Center Reade Amsterdam, Amsterdam, The Netherlands
  8. 8 Department of Paediatrics, Emma Children's Hospital AMC, University of Amsterdam, Amsterdam, The Netherlands
  9. 9 Department of Biostatistics, Leiden University Medical Center, Leiden, The Netherlands
  10. 10 Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands
  1. Correspondence to Petra Hissink Muller, Department of Paediatrics, Leiden University Medical Center, Leiden 9600, The Netherlands; p.hissinkmuller{at}


Question Which is the best strategy to achieve (drug-free) inactive disease in juvenile idiopathic arthritis (JIA)?

Methods In a randomised, single-blinded, study in disease-modifying anti-rheumatic drug (DMARD)-naive patients with JIA, three treatment-strategies were compared: (1) sequential DMARD-monotherapy (sulfasalazine or methotrexate (MTX)), (2) combination therapy MTX + 6 weeks prednisolone and (3) combination therapy MTX +etanercept. Treatment-to-target entailed 3-monthly DMARD/biological adjustments in case of persistent disease activity, with drug tapering to nil in case of inactive disease.

After 24 months, primary outcomes were time-to-inactive-disease and time-to-flare after DMARD discontinuation. Secondary outcomes were adapted ACRPedi30/50/70/90 scores, functional ability and adverse events.

Results 94 children (67 % girls) aged median (IQR) 9.1 (4.6–12.9) years were enrolled: 32 in arms 1 and 2, 30 in arm 3. At baseline visual analogue scale (VAS) physician was mean 49 (SD 16) mm, VAS patient 53 (22) mm, erythrocyte sedimentation rate 12.8 (14.7), active joints median 8 (5–12), limited joints 2.5 (1–4.8) and Childhood Health Assessment Questionnaire score mean 1.0 (0.6).

After 24 months, 71% (arm 1), 70% (arm 2) and 72% (arm 3) of patients had inactive disease and 45% (arm 1), 31% (arm 2) and 41% (arm 3) had drug-free inactive disease. Time-to-inactive-disease was median 9.0 (5.3–15.0) months in arm 1, 9.0 (6.0–12.8) months in arm 2 and 9.0 (6.0–12.0) months in arm 3 (p=0.30). Time-to-flare was not significantly different (overall 3.0 (3.0–6.8) months, p=0.7). Adapted ACR pedi-scores were comparably high between arms. Adverse events were similar.

Conclusion Regardless of initial specific treatments, after 24 months of treatment-to-target aimed at drug-free inactive disease, 71% of recent-onset patients with JIA had inactive disease (median onset 9 months) and 39% were drug free. Tightly controlled treatment-to-target is feasible.

Trial registration number 1574.

  • juvenile idiopathic arthritis
  • treatment-to-target
  • treatment strategy study
  • inactive disease

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  • Handling editor Josef S Smolen

  • Contributors All authors were involved in drafting the article or revising it critically for important intellectual content. All authors approved the final version to be published. HM had full access to all data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study conception and design: DMCB, CFA, RtC, LWAvS-S, MVR. Acquisition of data: PHM, DMCB, DS-M, Y-KK, JMvdB, TWK, ICJB, PWB, MVR, LWAvS-S, CFA, RtC. Analysis and interpretation of data: PHM, JMvdB, SB, DMCB, LWAvS-S, CFA, RtC. Critically revising the manuscript; DMCB, DS-M, YK-K, IB, WBvdB, WPB, TWK, MAJvR, LWAvS-S, JMvdB, CFA, RtC.

  • Funding This is an investigator-initiated study which received financial support from Pfizer, who had no role in study design, data collection, data analysis, data interpretation, writing of an abstract, or decision to submit a manuscript for submission.

  • Competing interests None declared.

  • Ethics approval Approval of the Medical Ethical Committee of the Leiden University Medical Center and local Ethical Committees was obtained prior to start at each study site.

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

  • Data statement The datasets used and/or analysed during the current study available from the corresponding author on reasonable request.