IL-6 blockade in systemic juvenile idiopathic arthritis – achievement of inactive disease and remission (data from the German AID-registry)

BIELAK, Maciej; Husmann, E; Weyandt, N.; Haas, Johannes‐Peter; Hügle, Boris; Horneff, Gerd; Neudorf, Ulrich; Lutz, Thomas; Lilienthal, Eggert; Kallinich, Tilmann; Tenbrock, Klaus; Berendes, R.; Niehues, Tim; Wittkowski, Helmut; Weißbarth‐Riedel, Elisabeth; Heubner, Georg; Oommen, Prasad T.; Klotsche, Jens; Foell, Dirk; Lainka, Elke

doi:10.1186/s12969-018-0236-y

Cited by 31 publications

(26 citation statements)

References 39 publications

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“…The relatively high usage of anti‐TNF in our cohort could be explained by their availability prior to anti‐IL agents (anti‐IL‐1 and anti‐IL‐6) and high percentage of patients with chronic arthritis in our cohort. The increased usage of anti‐IL‐1 and anti‐IL‐6 in sJIA patients recently provided significant improvement in sJIA treatment . In a routine practice, we use tocilizumab for patients resistant to standard treatment with predominantly joint involvement.…”

Section: Discussionmentioning

confidence: 99%

Prognosis, complications and treatment response in systemic juvenile idiopathic arthritis patients: A single‐center experience

et al. 2019

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Aim Systemic juvenile idiopathic arthritis (sJIA) is a distinctive subtype of JIA characterized by systemic features and poor outcome. We aimed to investigate demographic and clinical features, long‐term treatment response and disease complications in a large sJIA cohort. Methods Patients diagnosed with sJIA followed up at a pediatric rheumatology outpatient department from January 2003 to December 2017 were included. Demographic and clinical features, long‐term treatment response and disease complications were retrospectively collected. Results A total of 168 sJIA patients (51.8% female, 48.2% male) were included: 31.5% with monocyclic, 13.7% polycyclic and 54.8% with persistent clinical course. Corticosteroids were initially used in all patients. Methotrexate was used in 75% and cyclosporine A was used in 17.3% patients. Biological drugs were used in 42.8% patients; etanercept in 29.7%, anakinra in 16%, canakinumab in 16%, tocilizumab in 10% patients. Remission off medication was achieved in 82 (48.8%). Macrophage activation syndrome (MAS) was present in 11.9%, growth retardation in 11.3% patients. Eight percent (4/50) of patients had low bone mineral density. Three patients (1.78%) died due to MAS secondary multiorgan insufficiency and infection. Conclusion The disease is characterized with diverse clinical presentation and possibly severe complications. MAS complicated with multiorgan insufficiency is the major mortality factor. Corticosteroids represent the mainstay of the initial treatment. In patients resistant to classic treatment, biological drugs should be timely introduced.

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Section: Discussionmentioning

confidence: 99%

Prognosis, complications and treatment response in systemic juvenile idiopathic arthritis patients: A single‐center experience

et al. 2019

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“…Previous studies have demonstrated that pro-inflammatory cytokines IL-1β, IL-6, TNF-α and IFN-γ markedly increased in sJIA patients and were closely related to the inflammation of sJIA [ 3 , 28 ]. Clinical trials showed that antibodies of these pro-inflammatory cytokines could effectively alleviate the disease severity in patients with sJIA [ 7 , 34 – 36 ]. Therefore, blocking these cytokines expression is a promising strategy for the development of novel anti-sJIA therapies.…”

Section: Discussionmentioning

confidence: 99%

Plasma interleukin-37 is increased and inhibits the production of inflammatory cytokines in peripheral blood mononuclear cells in systemic juvenile idiopathic arthritis patients

Mao

Kang

et al. 2018

J Transl Med

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BackgroundInterleukin (IL)-37 has emerged as a novel anti-inflammatory cytokine that play an immunosuppressive role in regulating inflammatory response. This study aimed to measure IL-37 levels in the plasma and peripheral blood mononuclear cells (PBMCs) of patients with systemic juvenile idiopathic arthritis (sJIA), and to establish the correlation between IL-37 levels and disease activity, laboratory parameters and inflammatory cytokines.MethodsThe mRNA levels of IL-37 in PBMCs and plasma IL-37 concentrations in 46 sJIA patients and 30 age- and sex-matched healthy controls were measured by real-time polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. The correlations between plasma IL-37 levels and disease activity, laboratory parameters and inflammatory cytokines in sJIA were analyzed by Spearman correlation test. PBMCs from the sJIA patients were stimulated with recombinant human IL-37 (rhIL-37) protein, expressions of IL-1β, IL-6, TNF-α and IL-17 were detected by RT-PCR and ELISA.ResultsPlasma levels of IL-37 and relative IL-37 mRNA expression were significantly elevated in sJIA patients, especially in active sJIA patients, when compared with the healthy controls (P < 0.001). Furthermore, patients with active disease showed higher IL-37 mRNAs and plasma protein levels than those with inactive disease as well as healthy controls. Plasma IL-37 levels were correlated with disease activity and inflammatory cytokines (IL-6, TNF-α, IL-17 and GM-CSF) in sJIA patients. The productions of inflammatory cytokines such as IL-6, TNF-α, IL-17 in PBMCs from sJIA patients were obviously decreased after recombinant IL-37 stimulation, whereas the production of IL-1β was not changed.ConclusionsOur results demonstrate that levels of IL-37 were higher in sJIA patients, which were correlated with disease activity and sJIA related inflammatory cytokines. In addition, rhIL-37 down-regulates the expressions of inflammatory cytokines form PBMCs in sJIA patients, suggesting that IL-37 may have the potential role as a natural inhibitor for the pathogenesis and therapy of sJIA.Electronic supplementary materialThe online version of this article (10.1186/s12967-018-1655-8) contains supplementary material, which is available to authorized users.

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“…The clinical response in patients with systemic JIA was formally assessed according to the following response categories: 1) a good response, if the signs and symptoms of active disease (fever, rash, adenopathy, hepatosplenomegaly, serositis, and arthritis) had resolved and if the levels of inflammation markers (C‐reactive protein [CRP] and erythrocyte sedimentation rate [ESR]) had improved by at least 50% following treatment with anakinra and/or canakinumab, and if this response was maintained for at least 6 months; 2) a transient response, if there was an initial response characterized according to the parameters of a good response for at least 2 months but with later recurrence of disease; or 3) a poor response, if the parameters for improvement were not met. These treatment response criteria had been previously established for the purpose of a separate analysis of the AID registry cohort .…”

Section: Methodsmentioning

confidence: 99%

Impact of IL1RN Variants on Response to Interleukin‐1 Blocking Therapy in Systemic Juvenile Idiopathic Arthritis

Hinze

Fuehner

Kessel

et al. 2020

Arthritis & Rheumatology

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Objective To analyze the reported association of IL1RN polymorphisms with response to interleukin‐1 (IL‐1) blockade in a German cohort of patients with systemic juvenile idiopathic arthritis (JIA), and to assess the impact of other factors on treatment response. Methods Sixty‐one patients with systemic JIA who had received IL‐1 blockade were identified within the German Autoinflammatory Disease registry DNA biobank. Response to IL‐1 blockade was assessed according to 1) the clinical response (initially at least a transient response or good response compared to a poor response), 2) switch (or no switch) to anti–IL‐6 receptor therapy following IL‐1 blockade, 3) achievement of clinically inactive disease within 6 months of IL‐1 blockade, 4) improvement in disease activity measured using the modified Juvenile Arthritis Disease Activity Score, and 5) achievement of a glucocorticoid‐free state. In addition, basic demographic data, key features of the disease course, laboratory data, and IL1RN single‐nucleotide polymorphisms (SNPs) were assessed. Results Six of 7 IL1RN SNPs reported to be associated with response to anakinra therapy were analyzed. These 6 IL1RN SNPs were inherited as haplotypes. An association of IL1RN haplotypes and SNPs with response to IL‐1 blockade could not be confirmed in this cohort of patients with systemic JIA. Patients who received tocilizumab following IL‐1 blockade had a longer duration from disease onset to diagnosis than those who did not receive tocilizumab (median 0.27 years versus 0.08 years). Conclusion The results of this study could not confirm an impact of IL1RN SNPs on response to IL‐1 blockade therapy with either anakinra or canakinumab in a cohort of patients with systemic JIA. However, a longer time frame from disease onset to diagnosis was associated with poorer long‐term treatment response, thereby supporting the “window of opportunity” hypothesis that suggests improved long‐term treatment response with shorter time from disease onset to diagnosis (and treatment).

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IL-6 blockade in systemic juvenile idiopathic arthritis – achievement of inactive disease and remission (data from the German AID-registry)

Cited by 31 publications

References 39 publications

Prognosis, complications and treatment response in systemic juvenile idiopathic arthritis patients: A single‐center experience

Prognosis, complications and treatment response in systemic juvenile idiopathic arthritis patients: A single‐center experience

Plasma interleukin-37 is increased and inhibits the production of inflammatory cytokines in peripheral blood mononuclear cells in systemic juvenile idiopathic arthritis patients

Impact of IL1RN Variants on Response to Interleukin‐1 Blocking Therapy in Systemic Juvenile Idiopathic Arthritis

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