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Long-term outcome of juvenile idiopathic arthritis following a placebo-controlled trial: sustained benefits of early sulfasalazine treatment
  1. Marion A J van Rossum1,
  2. Renée M van Soesbergen2,
  3. Maarten Boers3,
  4. Aeilko H Zwinderman4,
  5. Theo J W Fiselier5,
  6. Marcel J A M Franssen6,
  7. Rebecca ten Cate7,
  8. Lisette W A van Suijlekom-Smit8,
  9. Nico M Wulffraat9,
  10. Wietse Kuis9,
  11. Wilma H J van Luijk10,
  12. Johanna C M Oostveen11,
  13. Ben A C Dijkmans12,
  14. on behalf of the Dutch Juvenile Idiopathic Arthritis Study group
  1. 1
    Emma Children’s Hospital AMC, Amsterdam, The Netherlands, and Department of Rheumatology, Jan van Breemen Instituut, Amsterdam, The Netherlands
  2. 2
    Department of Rheumatology, Jan van Breemen Instituut, Amsterdam, The Netherlands
  3. 3
    Department of Clinical Epidemiology and Biostatistics, VU University Medical Centre, Amsterdam, The Netherlands
  4. 4
    Department of Clinical Epidemiology and Biostatistics, Academic Medical Centre, Amsterdam, The Netherlands
  5. 5
    Department of Paediatrics, Radboud University Medical Centre, Nijmegen, The Netherlands
  6. 6
    Department of Rheumatology, St Maartenskliniek, Nijmegen, The Netherlands
  7. 7
    Department of Paediatrics, Leiden University Medical Centre, Leiden, The Netherlands and Department of Paediatrics, Erasmus MC/Sophia Children’s Hospital, Rotterdam, The Netherlands
  8. 8
    Department of Paediatrics, Erasmus MC/Sophia Children’s Hospital, Rotterdam, The Netherlands
  9. 9
    Department of Paediatrics, University Medical Centre Utrecht, Utrecht, The Netherlands
  10. 10
    Department of Paediatrics, University Medical Centre Groningen, Groningen, The Netherlands
  11. 11
    Department of Rheumatology, Twenteborg Ziekenhuis, Almelo, The Netherlands
  12. 12
    Department of Rheumatology, VU University Medical Centre, Amsterdam, The Netherlands, and Department of Rheumatology, Jan van Breemen Instituut, Amsterdam, The Netherlands
  1. Marion A J van Rossum, MD, PhD, Paediatric Rheumatologist, Emma Children’s Hospital AMC, Paediatric Rheumatology, G8-205, PO Box 22660, 1100 DD Amsterdam, The Netherlands; m.a.vanrossum{at}amc.uva.nl

Abstract

Objectives: A previous 24-week randomised trial demonstrated that sulfasalazine (SSZ) treatment was superior to placebo (PLAC) in suppressing disease activity in patients with oligo- and polyarticular onset juvenile idiopathic arthritis (JIA). The current study determines the long-term outcome of the trial participants and evaluates whether the benefits of SSZ allocation are sustained over time.

Methods: Between 2001 and 2003, 32 SSZ and 29 PLAC patients (90% of all patients) were prospectively examined clinically and by chart review, median 9 years (range 7 to 10) after trial inclusion. In the follow-up assessment, variables of the American College of Rheumatology Pediatric 30 (ACR Pedi 30) criteria were collected. The assessor was blinded to trial treatment allocation.

Results: After the trial, patients had been routinely followed in rheumatology referral centres, and treated at the discretion of the attending physician. Almost all patients continued or started disease-modifying antirheumatic drugs (DMARDs) (SSZ 91%, PLAC 93%; SSZ treatment in about 80%). DMARD treatment appeared less intensive in the SSZ group as evidenced by a significantly shorter duration of SSZ use (median 2.5 vs 5.2 years; p = 0.02) and a trend towards less use of methotrexate and other DMARDs. More than one-third of the patients reported long periods of non-compliance with DMARD treatment in both groups.

At follow-up, 74% of the patients had active joints, and 30% showed active polyarthritis. Almost all outcome scores were better for SSZ compared with PLAC patients. Differences (often exceeding 50%) were significant for the number of active joints, patients’ overall well-being, number of patients with episodes of clinical remission off medication (CROM) and duration of these episodes, patients in CROM and ACR Pedi 30 response at follow-up. Additional exploratory analyses performed to detect potential confounders related to patient characteristics or follow-up treatment showed that DMARD treatment compliance was positively correlated with an ACR Pedi 30 response (odds ratio 3.8, 95% confidence interval (CI) 1.1 to 13.4; p = 0.03). Adjusted for compliance, an SSZ patient was 4.2 times as likely as a PLAC patient to be an ACR Pedi 30 responder at follow-up (95% CI 1.3 to 14.3; p = 0.02).

Conclusions: This follow-up study shows that effective suppression of disease activity by SSZ treatment early in active disease in JIA patients has beneficial effects that persist for many years. Given these results, compliance with DMARD treatment deserves serious attention.

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Footnotes

  • Competing interests: None declared.

  • Abbreviations:
    CROM
    clinical remission off medication
    DMARD
    disease-modifying antirheumatic drug
    IQR
    interquartile range
    JIA
    juvenile idiopathic arthritis
    LOM
    limitation in range of motion
    MTX
    methotrexate
    NSAID
    nonsteroidal anti-inflammatory
    PGAS
    physician’s global assessment of disease activity score
    PLAC
    placebo
    SSZ
    sulfasalazine

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