Long-term outcome of juvenile idiopathic arthritis following a placebo-controlled trial: sustained benefits of early sulfasalazine treatment

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 onethird 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.

Factors Associated With Treatment Response to Etanercept in Juvenile Idiopathic Arthritis

“…The observation that the achievement of better outcomes was related with earlier treatment introduction has been reported previously for methotrexate and sulfasalazine. 5,6 In this study, the strongest association with a poor response to etanercept was the systemic-onset JIA. Systemic-onset JIA patients had 3-times higher odds to achieve a poor treatment outcome compared with the nonsystemic JIA categories and more systemic-onset JIA patients discontinued etanercept over time.…”

Therapeutic advancements in juvenile idiopathic arthritis

“…Approximately 30% of the SSZ-treated patients withdrew due to adverse events, which was much higher than the placebo group. A follow-up study of these same patients 7-10 years later showed sustained benefits [44]. Alternatively, in another small 26-week randomized, doubleblind, placebo-controlled study, no significant differences in active joint count, tender entheses count, pain visual analog scale, or spinal flexion were seen between SSZ and placebo [45].…”

Treatment of juvenile idiopatic arthritis and biological agents

“…Bu süre içerisinde aktif artritli eklem sayısı, hastanın genel iyilik halini değerlendirmesi, ACR Pedi 30 cevapları, klinik remisyon gösteren hasta sayısı ve remisyon süreleri gibi parametreler takip edilmiş, bu parametrelerde plasebo grubuna kıyasla daha fazla düzelme olduğu iddia edilmiştir. 23 Pek çok çalışmada, sülfasalazinin artriti iyileştirdiği, özellik-le JIA'in oligo ve poliartiküler formunda etkili olduğu gös-terilmiştir. [22][23][24][25] Sülfasalazin tedavisi sırasında en sık gözlenen yan etkilerin döküntü, gastrointestinal semptomlar ve lökopeni olduğu bildirilmiştir.…”