Urinary interleukin-6 as a predictor of radiographic progression in rheumatoid arthritis: A 3-year evaluation

Joo, Young Bin; Yoo, Sehoon; Kım, Garam; Cho, Chul-Soo; Kim, Wan‐Uk

doi:10.1038/srep35242

Cited by 8 publications

(12 citation statements)

References 50 publications

(74 reference statements)

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“…In our study, IL-6 level was significantly higher in RA patients with a high DAS28 score compared to those with lower scores. Meanwhile, high IL-6 level was shown to be an independent risk factor for high disease activity in RA, as reflected by the DAS28 score (Park et al, 2016), and alters the Treg/Th17 balance by downregulating IL-6 (Samson et al, 2012). These results suggest that regulating cytokine levels and lymphocyte subpopulations may be an effective strategy in controlling disease activity in RA.…”

Section: Discussionmentioning

confidence: 91%

Characteristics of the Gut Microbiome and Its Relationship With Peripheral CD4+ T Cell Subpopulations and Cytokines in Rheumatoid Arthritis

et al. 2022

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This study investigated the association between intestinal microbiota abundance and diversity and cluster of differentiation (CD)4+ T cell subpopulations, cytokine levels, and disease activity in rheumatoid arthritis RA. A total of 108 rheumatoid arthritis (RA) patients and 99 healthy control (HC) subjects were recruited. PICRUSt2 was used for functional metagenomic predictions. Absolute counts of peripheral CD4+ T cell subpopulations and cytokine levels were detected by flow cytometry and with a cytokine bead array, respectively. Correlations were analyzed with the Spearman rank correlation test. The results showed that the diversity of intestinal microbiota was decreased in RA patients compared to HCs. At the phylum level, the abundance of Firmicutes, Fusobacteriota, and Bacteroidota was decreased while that of Actinobacteria and Proteobacteria was increased and at the genus level, the abundance of Faecalibacterium, Blautia, and Escherichia-Shigella was increased while that of Bacteroides and Coprococcus was decreased in RA patients compared to HC subjects. The linear discriminant analysis effect size indicated that Bifidobacterium was the most significant genus in RA. The most highly enriched Kyoto Encyclopedia of Genes and Genomes pathway in RA patients was amino acid metabolism. The relative abundance of Megamonas, Monoglobus, and Prevotella was positively correlated with CD4+ T cell counts and cytokine levels; and the relative numbers of regulatory T cells (Tregs) and T helper (Th17)/Treg ratio were negatively correlated with disease activity in RA. These results suggest that dysbiosis of certain bacterial lineages and alterations in gut microbiota metabolism lead to changes in the host immune profile that contribute to RA pathogenesis.

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Section: Discussionmentioning

confidence: 91%

Characteristics of the Gut Microbiome and Its Relationship With Peripheral CD4+ T Cell Subpopulations and Cytokines in Rheumatoid Arthritis

et al. 2022

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“…Patients with RA have elevated levels of interleukin-6 (IL-6) in serum and synovial fluid (9,10). IL-6 drives inflammation and promotes articular destruction, is involved in the development of extraarticular manifestations, and correlates with disease activity (10)(11)(12).…”

Section: Introductionmentioning

confidence: 99%

Association of High Serum Interleukin‐6 Levels With Severe Progression of Rheumatoid Arthritis and Increased Treatment Response Differentiating Sarilumab From Adalimumab or Methotrexate in a Post Hoc Analysis

Boyapati

Schwartzman

Msihid

et al. 2020

Arthritis & Rheumatology

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Objective The development of biomarkers to guide treatment decisions is a major research focus in rheumatoid arthritis (RA). Patients with RA have elevated interleukin‐6 (IL‐6) levels; however, the utility of IL‐6 as a predictor of treatment response is unclear. This study was undertaken to investigate, by post hoc analysis, whether baseline IL‐6 levels are predictive of sarilumab treatment responses in 2 phase III studies. Methods Serum IL‐6 concentrations were measured in patients with RA prior to receiving sarilumab 200 mg (n = 148) or adalimumab 40 mg (n = 152) every 2 weeks (in the MONARCH trial; ClinicalTrials.gov identifier: NCT02332590) or sarilumab 150 mg, sarilumab 200 mg, or placebo every 2 weeks plus methotrexate (MTX) (n = 401, n = 396, and n = 397, respectively) (in the MOBILITY trial; ClinicalTrials.gov identifier: NCT01061736). Efficacy and patient‐reported outcomes were compared between and within groups according to IL‐6 tertile using linear and logistic regression. Results In MONARCH, patients with high baseline IL‐6 levels (all ≥3 times the upper limit of normal; n = 100) had higher disease activity at baseline than those with low IL‐6 levels (n = 100). The magnitude of clinical improvement over 24 weeks with sarilumab versus adalimumab was greater in patients with high compared to those with low baseline IL‐6 levels. In MOBILITY, compared to patients with low IL‐6 levels (n = 397), patients with high IL‐6 levels (n = 398) had higher disease activity and joint damage at baseline, were more likely to have joint progression, and had less clinical improvement over 52 weeks’ treatment with placebo plus MTX compared to sarilumab 150 mg or 200 mg plus MTX. Baseline IL‐6 and C‐reactive protein levels were both predictive of outcomes. Safety profiles were similar between defined IL‐6 tertiles. Conclusion IL‐6 may be a prognostic marker of disease progression and severity, and patients with high IL‐6 levels may be likely to benefit from sarilumab compared to adalimumab or MTX. Prospective validation is warranted to confirm the results of these post hoc analyses.

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“…Chronic systemic inflammation is implicated in the pathogenesis of both RA and diabetes [6]. The proinflammatory cytokines interleukin (IL)-6, tumour necrosis factor-α (TNFα) and IL-1β play key roles in the synovial inflammation and joint damage associated with RA and also have systemic effects on extra-articular tissues [7][8][9]. IL-6 can signal through both membranebound (cis-signalling) and soluble (trans-signalling) IL-6 receptors (IL-6Rs) and therefore has pleiotropic effects on immune/inflammatory and other cell types, such as pancreatic β cells, skeletal muscle, adipose tissue and liver [10,11].…”

Section: Introductionmentioning

confidence: 99%

Interleukin-6 receptor blockade or TNFα inhibition for reducing glycaemia in patients with RA and diabetes: post hoc analyses of three randomised, controlled trials

et al. 2020

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Background Diabetes is common in patients with rheumatoid arthritis (RA). Interleukin (IL)-6 is implicated in both the pathogenesis of RA and in glucose homeostasis; this post hoc analysis investigated the effects of IL-6 receptor vs. tumour necrosis factor inhibition on glycosylated haemoglobin (HbA1c) in patients with RA with or without diabetes. Methods Data were from two placebo-controlled phase III studies of subcutaneous sarilumab 150/200 mg q2w + methotrexate or conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and a phase III monotherapy study of sarilumab 200 mg q2w vs. adalimumab 40 mg q2w. Patients with diabetes were identified by medical history or use of antidiabetic medication (patients with HbA1c ≥ 9% were excluded from all three studies). HbA1c was measured at baseline and weeks 12/24. Safety and efficacy were assessed in RA patients with or without diabetes. Results Patients with diabetes (n = 184) were older, weighed more and exhibited higher RA disease activity than patients without diabetes (n = 1928). Regardless of diabetes status, in patients on background csDMARDs, least squares (LS) mean difference (95% CI) in change from baseline in HbA1c for sarilumab 150 mg/200 mg vs. placebo at week 24 was − 0.28 (− 0.40, − 0.16; nominal p < 0.0001) and − 0.42 (− 0.54, − 0.31; nominal p < 0.0001), respectively. Without csDMARDs, LS mean difference for sarilumab 200 mg vs. adalimumab 40 mg at week 24 was − 0.13 (− 0.22, − 0.04; nominal p = 0.0043). Greater reduction in HbA1c than placebo or adalimumab was observed at week 24 with sarilumab in patients with diabetes and/or baseline HbA1c ≥ 7%. There was no correlation between baseline/change from baseline in HbA1c and baseline/change from baseline in C-reactive protein, 28-joint Disease Activity Score, or haemoglobin, nor between HbA1c change from baseline and baseline glucocorticoid use. Medical history of diabetes or use of diabetes treatments had limited impact on safety and efficacy of sarilumab and was consistent with overall phase III findings in patients with RA. Conclusions In post hoc analyses, sarilumab was associated with a greater reduction in HbA1c than csDMARDs or adalimumab, independent of sarilumab anti-inflammatory effects. Prospective studies are required to further assess these preliminary findings. Trial registration ClinTrials.gov NCT01061736: date of registration February 03, 2010; ClinTrials.gov NCT01709578: date of registration October 18, 2012; ClinTrials.gov NCT02332590: date of registration January 07, 2015.

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Urinary interleukin-6 as a predictor of radiographic progression in rheumatoid arthritis: A 3-year evaluation

Cited by 8 publications

References 50 publications

Characteristics of the Gut Microbiome and Its Relationship With Peripheral CD4+ T Cell Subpopulations and Cytokines in Rheumatoid Arthritis

Characteristics of the Gut Microbiome and Its Relationship With Peripheral CD4+ T Cell Subpopulations and Cytokines in Rheumatoid Arthritis

Association of High Serum Interleukin‐6 Levels With Severe Progression of Rheumatoid Arthritis and Increased Treatment Response Differentiating Sarilumab From Adalimumab or Methotrexate in a Post Hoc Analysis

Interleukin-6 receptor blockade or TNFα inhibition for reducing glycaemia in patients with RA and diabetes: post hoc analyses of three randomised, controlled trials

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