Proinflammatory Cytokines in Monitoring the Course of Disease and Effectiveness of Treatment with Etanercept (ETN) of children with Oligo- and Polyarticular Juvenile Idiopathic Arthritis (JIA)

Kaminiarczyk-Pyzalka, Dominika; Adamczak, Karolina; Mikos, Hanna; Klimecka, Iwona; Moczko, Jerzy; Niedziela, Marek

doi:10.7754/clin.lab.2013.130734

Cited by 17 publications

(24 citation statements)

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“…Following the patients over 6 months allowed for the evaluation of a temporal relationship between initiation of drug therapy, changes in cytokine concentrations, and changes in disease activity. Most notably, these findings are in line with previous observations that concentrations of IL‐6 and TNF‐α are proportional to disease activity and support their role in the pathogenesis of JIA, as well as their viability as a drug target in this population . Further, these findings support the role of routine monitoring of TNF‐α and IL‐6 levels in the treatment of patients with JIA.…”

Section: Discussionsupporting

confidence: 89%

“…Studies of healthy subjects and biological DMARD‐naive patients with JIA have similarly demonstrated increased TNF‐α and IL‐6 levels in this disease population . However, after initiation of therapy, only IL‐6 level was consistently associated with disease activity . In these studies, patients were treated with anti–TNF‐α biologics that likely confounded the relationship of TNF‐α with disease activity, as demonstrated in our study.…”

Section: Discussionsupporting

confidence: 61%

“…Consistent with the role of IL‐6 and TNF‐α in the pathogenesis of JIA, plasma concentrations of these cytokines correlated with baseline disease activity. Studies of healthy subjects and biological DMARD‐naive patients with JIA have similarly demonstrated increased TNF‐α and IL‐6 levels in this disease population . However, after initiation of therapy, only IL‐6 level was consistently associated with disease activity .…”

Section: Discussionmentioning

confidence: 86%

“…Proinflammatory cytokines have been implicated in the pathogenesis of JIA and other autoimmune diseases and have been a target of pharmaceutical development, resulting in multiple new drugs for JIA . The recognition that tumor necrosis factor‐α (TNF‐α) is highly expressed in the tissues of patients with active disease resulted in the development of several agents targeting this proinflammatory mediator . The identification of interleukin (IL)‐6 and the IL‐1 family of cytokines as important mediators in the pathogenesis of JIA has similarly resulted in the development of agents targeting these pathways .…”

mentioning

confidence: 99%

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Cytokine Biomarkers of Disease Activity and Therapeutic Response after Initiating Methotrexate Therapy in Patients with Juvenile Idiopathic Arthritis

2017

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Plasma cytokine levels were responsive to MTX therapy in patients with JIA, but only TNF-α and IL-6 levels were consistently associated with disease activity and therapeutic response. Increased TNF-α levels at baseline were associated with failure to respond to standard-dose MTX and the need for more aggressive drug therapy. Initiation of ETN resulted in increased TNF-α levels that corresponded with therapeutic response, suggesting a potential clinical benefit of monitoring TNF-α levels as a pharmacodynamic marker of etanercept activity.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionsupporting

confidence: 61%

Section: Discussionmentioning

confidence: 86%

mentioning

confidence: 99%

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Cytokine Biomarkers of Disease Activity and Therapeutic Response after Initiating Methotrexate Therapy in Patients with Juvenile Idiopathic Arthritis

2017

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“…However, levels were drawn in subjects already on etanercept therapy, and baseline levels of TNF-a were not checked in this study. A single prospective study found that JIA patients who had failed treatment with DMARDS and corticosteroids also had increased TNF-a levels during treatment with etanercept, and this occurred irrespective of clinical course [23]. This study did not evaluate other TNF-a inhibitors and did not follow a JIA cohort unexposed to TNF-a inhibitor therapy in parallel.…”

Section: Discussionmentioning

confidence: 99%

The impact of disease activity and tumour necrosis factor-α inhibitor therapy on cytokine levels in juvenile idiopathic arthritis

Walters

Pan

Lehman

et al. 2016

Clinical and Experimental Immunology

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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.

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Treatment response to etanercept in methotrexate refractory juvenile idiopathic arthritis: an analysis of predictors and long-term outcomes

Yang

Chiang

2017

Clin Rheumatol

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The aim of the study is to evaluate the long-term outcomes, predictors, and the role of inflammatory cytokines in methotrexate (MTx) refractory juvenile idiopathic arthritis (JIA) patients. This is a retrospective cohort study. MTx refractory JIA patients who received etanercept as their first biological agent in National Taiwan University Hospital (NTUH) were enrolled. Patients were classified into remission group, non-remission group, relapsing group, and non-relapsing group according to the criteria of disease remission and disease flares defined by Wallace et al. We compared the differences in the baseline data, therapeutic responses, time to etanercept tapering, and inflammatory cytokine (IL-12p70, TNF-α, IL-10, IL-6, and IL-1β) levels between these groups. Among the 58 patients, 30 (52%) reached remission. Seventeen of the 30 patients had episodes of disease flares. We found that more patients in the remission group achieved ACR pediatric 70 response at the fourth month after etanercept treatment (p < 0.002). When comparing the relapsing group and non-relapsing group, we found that patients were more likely to have disease flares if it took longer to achieve remission (p = 0.0008). Besides, etanercept was tapered earlier in the non-relapsing group (p = 0.0006). There was no significant difference in levels of inflammatory cytokine between groups. No parameter before treatment could be used as a single predictor of long-term outcomes. However, ACR pediatric 70 response at the fourth month after etanercept treatment might predict disease remission. Besides, patients who achieved remission more rapidly were less likely to have disease flares.

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Proinflammatory Cytokines in Monitoring the Course of Disease and Effectiveness of Treatment with Etanercept (ETN) of children with Oligo- and Polyarticular Juvenile Idiopathic Arthritis (JIA)

Cited by 17 publications

References 0 publications

Cytokine Biomarkers of Disease Activity and Therapeutic Response after Initiating Methotrexate Therapy in Patients with Juvenile Idiopathic Arthritis

Cytokine Biomarkers of Disease Activity and Therapeutic Response after Initiating Methotrexate Therapy in Patients with Juvenile Idiopathic Arthritis

The impact of disease activity and tumour necrosis factor-α inhibitor therapy on cytokine levels in juvenile idiopathic arthritis

Treatment response to etanercept in methotrexate refractory juvenile idiopathic arthritis: an analysis of predictors and long-term outcomes

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