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Aggressive Combination Drug Therapy in Very Early Polyarticular Juvenile Idiopathic Arthritis (ACUTE–JIA): a multicentre randomised open-label clinical trial
  1. Pirjo Tynjälä1,
  2. Paula Vähäsalo2,
  3. Maarit Tarkiainen1,
  4. Liisa Kröger3,
  5. Kristiina Aalto1,
  6. Merja Malin4,
  7. Anne Putto-Laurila5,
  8. Visa Honkanen1,
  9. Pekka Lahdenne1
  1. 1Department of Pediatric Rheumatology, Children's Hospital, Helsinki University Central Hospital, Helsinki, Finland
  2. 2Department of Pediatrics, Oulu University Hospital, Oulu, Finland
  3. 3Department of Pediatrics, Kuopio University Hospital, Kuopio, Finland
  4. 4Department of Pediatrics, Tampere University Hospital, Tampere, Finland
  5. 5Department of Pediatrics, Turku University Hospital, Turku, Finland
  1. Correspondence to Pirjo Tynjälä, Research Unit, Hospital for Children and Adolescents, Biomedicum 2C Helsinki, PB 705, 00029 Hus, Finland; pirjo.tynjala{at}


Objectives In juvenile idiopathic arthritis (JIA), the efficacy of very early disease-modifying drug therapy, synthetic or biological, is not well known. Three alternative strategies were compared for treating recent‑onset polyarticular JIA.

Methods In a 54-week multicentre open-label clinical trial, 60 disease-modifying antirheumatic drug (DMARD)-naive patients aged 4–15 years were randomly assigned into three treatment arms. The efficacy of infliximab plus methotrexate (TNF) was compared to that of two synthetic therapies: methotrexate alone (MTX) and DMARD methotrexate, sulphasalazine and hydroxychloroquine in combination (COMBO). Primary endpoint was American College of Rheumatology paediatric 75% improvement (ACR Pedi 75). Secondary endpoints were inactive disease and safety.

Results In 59 patients, mean (±SE) age at baseline was 9.6±0.4 years, duration of JIA 1.9±0.2 months and number of active joints 18±1. ACR Pedi 75 was achieved in 100% (19/19) of patients receiving TNF, 65% (13/20) on COMBO (95% CI 44% to 86%) and 50% (10/20) on methotrexate (95% CI 28% to 72%) p<0.0001. Thirteen patients receiving TNF (68%; 95% CI 47% to 89%) achieved inactive disease, whereas eight (40%; 95% CI 22% to 63%) on COMBO and five (25%; 95% CI 6% to 44%) on methotrexate did (p=0.002). Patients on TNF spent a mean 26 weeks (95% CI 18 to 34) with inactive disease, longer than did those receiving COMBO (13 weeks; 95% CI 6 to 20), or methotrexate (6 weeks; 95% CI 2 to 10). Serious adverse events were rare.

Conclusion In early polyarticular JIA, targeting to achieve minimally active or inactive disease, infliximab plus methotrexate was superior to synthetic DMARD in combination and strikingly superior to methotrexate alone.

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  • VH and PL contributed equally to this work.

  • Funding This study was funded by research grants from Hospital Districts of Helsinki and Uusimaa, Oulu, Kuopio, Turku and Päijät-Häme; the Rheumatism Foundation Hospital; the Päivikki and Sakari Sohlberg Foundation; the Foundation for Pediatric Research, Finland; and the Scandinavian Rheumatology Research Foundation.

  • Competing interests VH is a current employee of UCB Pharma and reports ownership of stock options.

  • Patient consent Obtained.

  • Ethics approval This study was conducted with the approval of the Coordinating Ethical Committee, Helsinki University Central Hospital, Finland.

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

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