Long-term outcome of juvenile idiopathic arthritis following a placebo-controlled trial: sustained benefits of early sulfasalazine treatment.
OBJECTIVE
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.
van Rossum
Marion A J
MA
Emma Children's Hospital AMC, Paediatric Rheumatology, G8-205, PO Box 22660, 1100 DD Amsterdam, The Netherlands. m.a.vanrossum@amc.uva.nl
van Soesbergen
Renée M
RM
Boers
Maarten
M
Zwinderman
Aeilko H
AH
Fiselier
Theo J W
TJ
Franssen
Marcel J A M
MJ
ten Cate
Rebecca
R
van Suijlekom-Smit
Lisette W A
LW
Wulffraat
Nico M
NM
van Luijk
Wilma H J
WH
Oostveen
Johanna C M
JC
Kuis
Wietse
W
Dijkmans
Ben A C
BA
D000293:Adolescent; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001171:Arthritis, Juvenile / Q000188:drug therapy*; D002648:Child; D002675:Child, Preschool; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004812:Epidemiologic Methods; D005260:Female; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D010349:Patient Compliance; D012720:Severity of Illness Index; D012460:Sulfasalazine / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome
D018501:Antirheumatic Agents; D012460:Sulfasalazine; D008727:Methotrexate