The impact of disease activity and tumour necrosis factor-α inhibitor therapy on cytokine levels in juvenile idiopathic arthritis. (13th April 2016)

• Record Type: Journal Article
• Authors: Walters, H M; Pan, N; Lehman, T J A; Adams, A; Kalliolias, G D; Zhu, Y S; Santiago, F; Nguyen, J; Sitaras, L; Cunningham-Rundles, S; Walsh, T J; Toussi, S S
• Is Part Of: Clinical and experimental immunology. Volume 184:Number 3(2016:Jun.)
• Page Start: 308
• Page End: 317
• Publication Date: 2016-04-13
• Subjects: arthritis -- autoimmunity -- cytokines; Immunopathology -- Periodicals; 616.079
• DOI: 10.1111/cei.12782
• Languages: English
• ISSNs: 0009-9104

Abstract

Summary: The aim of this study was to evaluate prospectively cytokine levels and disease activity in juvenile idiopathic arthritis (JIA) patients treated with and without tumour necrosis factor (TNF)-α inhibitors. TNF-α inhibitor-naive JIA subjects were followed prospectively for 6 months. Cytokine levels of TNF-α, interleukin (IL)−1β, IL-6, IL-8, IL-10 and IL-17 were measured at baseline for JIA subjects and healthy controls (HCs). Cytokine levels were then measured at four time-points after initiation of TNF-α inhibition for anti-TNF-α-treated (anti-TNF) JIA subjects, and at two subsequent time-points for other JIA (non-TNF) subjects. JIA disease activity by Childhood Health Assessment Questionnaire (CHAQ) disability index/pain score and physician joint count/global assessment was recorded. Sixteen anti-TNF, 31 non-TNF and 16 HCs were analysed. Among JIA subjects, those with higher baseline disease activity (subsequent anti-TNFs) had higher baseline TNF-α, IL-6 and IL-8 than those with lower disease activity (non-TNFs) ( P < 0·05). TNF-α and IL-10 increased, and IL-6 and IL-8 no longer remained significantly higher after TNF-α inhibitor initiation in anti-TNF subjects. Subgroup analysis of etanercept versus adalimumab-treated subjects showed that TNF-α and IL-17 increased significantly in etanercept but not adalimumab-treated subjects, despite clinical improvement in both groups of subjects. JIA subjects with increased disease activity at baseline had higher serum proinflammatory cytokines. TNF-α inhibition resulted in suppression of IL-6 and IL-8 in parallel with clinical improvement in all anti-TNF-treated subjects, but was also associated with elevated TNF-α and IL-17 in etanercept-treated subjects.