Inflammatory biomarkers predicting long-term remission and active disease in juvenile idiopathic arthritis: a population-based study of the Nordic JIA cohort

Mia Glerup; Christoph Kessel; Dirk Foell; Lillemor Berntson; Anders Fasth; Charlotte Myrup; Ellen Nordal; Veronika Rypdal; Marite Rygg; Ellen Dalen Arnstad; Suvi Peltoniemi; Kristiina Aalto; Susanne Schleifenbaum; Malene Noer Høllsberg; Anders Ellern Bilgrau; Troels Herlin

doi:10.1136/rmdopen-2024-004317

Inflammatory biomarkers predicting long-term remission and active disease in juvenile idiopathic arthritis: a population-based study of the Nordic JIA cohort

Mia Glerup, Christoph Kessel, Dirk Foell, Lillemor Berntson, Anders Fasth, Charlotte Myrup, Ellen Nordal, Veronika Rypdal, Marite Rygg, Ellen Dalen Arnstad, Suvi Peltoniemi, Kristiina Aalto, Susanne Schleifenbaum, Malene Noer Høllsberg, Anders Ellern Bilgrau, Troels Herlin

Department of Clinical Medicine - Department of Paediatrics

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

Abstract

OBJECTIVES: To assess the ability of baseline serum biomarkers to predict disease activity and remission status in juvenile idiopathic arthritis (JIA) at 18-year follow-up (FU) in a population-based setting. METHODS: Clinical data and serum levels of inflammatory biomarkers were assessed in the longitudinal population-based Nordic JIA cohort study at baseline and at 18-year FU. A panel of 16 inflammatory biomarkers was determined by multiplexed bead array assay. We estimated both univariate and multivariate logistic regression models on binary outcomes of disease activity and remission with baseline variables as explanatory variables. RESULTS: Out of 349 patients eligible for the Nordic JIA cohort study, 236 (68%) had available serum samples at baseline. We measured significantly higher serum levels of interleukin 1β (IL-1β), IL-6, IL-12p70, IL-13, MMP-3, S100A9 and S100A12 at baseline in patients with active disease at 18-year FU than in patients with inactive disease. Computing receiver operating characteristics illustrating the area under the curve (AUC), we compared a conventional prediction model (gender, age, joint counts, erythrocyte sedimentation rate, C reactive protein) with an extended model that also incorporated the 16 baseline biomarkers. Biomarker addition significantly improved the ability of the model to predict activity/inactivity at the 18-year FU, as evidenced by an increase in the AUC from 0.59 to 0.80 (p=0.02). Multiple regression analysis revealed that S100A9 was the strongest predictor of inactive disease 18 years after disease onset. CONCLUSION: Biomarkers indicating inflammation at baseline have the potential to improve evaluation of disease activity and prediction of long-term outcomes.

Original language	English
Article number	e004317
Journal	RMD Open
Volume	10
Issue	3
ISSN	2056-5933
DOIs	https://doi.org/10.1136/rmdopen-2024-004317
Publication status	Published - Sept 2024

Keywords

Arthritis, Juvenile
Autoimmune Diseases
Child
Inflammation

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10.1136/rmdopen-2024-004317Licence: CC BY-NC

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Glerup, M., Kessel, C., Foell, D., Berntson, L., Fasth, A., Myrup, C., Nordal, E., Rypdal, V., Rygg, M., Arnstad, E. D., Peltoniemi, S., Aalto, K., Schleifenbaum, S., Høllsberg, M. N., Bilgrau, A. E., & Herlin, T. (2024). Inflammatory biomarkers predicting long-term remission and active disease in juvenile idiopathic arthritis: a population-based study of the Nordic JIA cohort. RMD Open, 10(3), Article e004317. https://doi.org/10.1136/rmdopen-2024-004317

@article{d63fdf37331947f8ae603279b226e28b,

title = "Inflammatory biomarkers predicting long-term remission and active disease in juvenile idiopathic arthritis: a population-based study of the Nordic JIA cohort",

abstract = "OBJECTIVES: To assess the ability of baseline serum biomarkers to predict disease activity and remission status in juvenile idiopathic arthritis (JIA) at 18-year follow-up (FU) in a population-based setting. METHODS: Clinical data and serum levels of inflammatory biomarkers were assessed in the longitudinal population-based Nordic JIA cohort study at baseline and at 18-year FU. A panel of 16 inflammatory biomarkers was determined by multiplexed bead array assay. We estimated both univariate and multivariate logistic regression models on binary outcomes of disease activity and remission with baseline variables as explanatory variables. RESULTS: Out of 349 patients eligible for the Nordic JIA cohort study, 236 (68%) had available serum samples at baseline. We measured significantly higher serum levels of interleukin 1β (IL-1β), IL-6, IL-12p70, IL-13, MMP-3, S100A9 and S100A12 at baseline in patients with active disease at 18-year FU than in patients with inactive disease. Computing receiver operating characteristics illustrating the area under the curve (AUC), we compared a conventional prediction model (gender, age, joint counts, erythrocyte sedimentation rate, C reactive protein) with an extended model that also incorporated the 16 baseline biomarkers. Biomarker addition significantly improved the ability of the model to predict activity/inactivity at the 18-year FU, as evidenced by an increase in the AUC from 0.59 to 0.80 (p=0.02). Multiple regression analysis revealed that S100A9 was the strongest predictor of inactive disease 18 years after disease onset. CONCLUSION: Biomarkers indicating inflammation at baseline have the potential to improve evaluation of disease activity and prediction of long-term outcomes.",

keywords = "Arthritis, Juvenile, Autoimmune Diseases, Child, Inflammation",

author = "Mia Glerup and Christoph Kessel and Dirk Foell and Lillemor Berntson and Anders Fasth and Charlotte Myrup and Ellen Nordal and Veronika Rypdal and Marite Rygg and Arnstad, {Ellen Dalen} and Suvi Peltoniemi and Kristiina Aalto and Susanne Schleifenbaum and H{\o}llsberg, {Malene Noer} and Bilgrau, {Anders Ellern} and Troels Herlin",

note = "Publisher Copyright: {\textcopyright} Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.",

year = "2024",

month = sep,

doi = "10.1136/rmdopen-2024-004317",

language = "English",

volume = "10",

journal = "RMD Open",

issn = "2056-5933",

publisher = "BMJ Publishing Group",

number = "3",

}

Glerup, M, Kessel, C, Foell, D, Berntson, L, Fasth, A, Myrup, C, Nordal, E, Rypdal, V, Rygg, M, Arnstad, ED, Peltoniemi, S, Aalto, K, Schleifenbaum, S, Høllsberg, MN, Bilgrau, AE & Herlin, T 2024, 'Inflammatory biomarkers predicting long-term remission and active disease in juvenile idiopathic arthritis: a population-based study of the Nordic JIA cohort', RMD Open, vol. 10, no. 3, e004317. https://doi.org/10.1136/rmdopen-2024-004317

Inflammatory biomarkers predicting long-term remission and active disease in juvenile idiopathic arthritis: a population-based study of the Nordic JIA cohort. / Glerup, Mia; Kessel, Christoph; Foell, Dirk et al.
In: RMD Open, Vol. 10, No. 3, e004317, 09.2024.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - Inflammatory biomarkers predicting long-term remission and active disease in juvenile idiopathic arthritis

T2 - a population-based study of the Nordic JIA cohort

AU - Glerup, Mia

AU - Kessel, Christoph

AU - Foell, Dirk

AU - Berntson, Lillemor

AU - Fasth, Anders

AU - Myrup, Charlotte

AU - Nordal, Ellen

AU - Rypdal, Veronika

AU - Rygg, Marite

AU - Arnstad, Ellen Dalen

AU - Peltoniemi, Suvi

AU - Aalto, Kristiina

AU - Schleifenbaum, Susanne

AU - Høllsberg, Malene Noer

AU - Bilgrau, Anders Ellern

AU - Herlin, Troels

PY - 2024/9

Y1 - 2024/9

N2 - OBJECTIVES: To assess the ability of baseline serum biomarkers to predict disease activity and remission status in juvenile idiopathic arthritis (JIA) at 18-year follow-up (FU) in a population-based setting. METHODS: Clinical data and serum levels of inflammatory biomarkers were assessed in the longitudinal population-based Nordic JIA cohort study at baseline and at 18-year FU. A panel of 16 inflammatory biomarkers was determined by multiplexed bead array assay. We estimated both univariate and multivariate logistic regression models on binary outcomes of disease activity and remission with baseline variables as explanatory variables. RESULTS: Out of 349 patients eligible for the Nordic JIA cohort study, 236 (68%) had available serum samples at baseline. We measured significantly higher serum levels of interleukin 1β (IL-1β), IL-6, IL-12p70, IL-13, MMP-3, S100A9 and S100A12 at baseline in patients with active disease at 18-year FU than in patients with inactive disease. Computing receiver operating characteristics illustrating the area under the curve (AUC), we compared a conventional prediction model (gender, age, joint counts, erythrocyte sedimentation rate, C reactive protein) with an extended model that also incorporated the 16 baseline biomarkers. Biomarker addition significantly improved the ability of the model to predict activity/inactivity at the 18-year FU, as evidenced by an increase in the AUC from 0.59 to 0.80 (p=0.02). Multiple regression analysis revealed that S100A9 was the strongest predictor of inactive disease 18 years after disease onset. CONCLUSION: Biomarkers indicating inflammation at baseline have the potential to improve evaluation of disease activity and prediction of long-term outcomes.

AB - OBJECTIVES: To assess the ability of baseline serum biomarkers to predict disease activity and remission status in juvenile idiopathic arthritis (JIA) at 18-year follow-up (FU) in a population-based setting. METHODS: Clinical data and serum levels of inflammatory biomarkers were assessed in the longitudinal population-based Nordic JIA cohort study at baseline and at 18-year FU. A panel of 16 inflammatory biomarkers was determined by multiplexed bead array assay. We estimated both univariate and multivariate logistic regression models on binary outcomes of disease activity and remission with baseline variables as explanatory variables. RESULTS: Out of 349 patients eligible for the Nordic JIA cohort study, 236 (68%) had available serum samples at baseline. We measured significantly higher serum levels of interleukin 1β (IL-1β), IL-6, IL-12p70, IL-13, MMP-3, S100A9 and S100A12 at baseline in patients with active disease at 18-year FU than in patients with inactive disease. Computing receiver operating characteristics illustrating the area under the curve (AUC), we compared a conventional prediction model (gender, age, joint counts, erythrocyte sedimentation rate, C reactive protein) with an extended model that also incorporated the 16 baseline biomarkers. Biomarker addition significantly improved the ability of the model to predict activity/inactivity at the 18-year FU, as evidenced by an increase in the AUC from 0.59 to 0.80 (p=0.02). Multiple regression analysis revealed that S100A9 was the strongest predictor of inactive disease 18 years after disease onset. CONCLUSION: Biomarkers indicating inflammation at baseline have the potential to improve evaluation of disease activity and prediction of long-term outcomes.

KW - Arthritis, Juvenile

KW - Autoimmune Diseases

KW - Child

KW - Inflammation

UR - http://www.scopus.com/inward/record.url?scp=85203610522&partnerID=8YFLogxK

U2 - 10.1136/rmdopen-2024-004317

DO - 10.1136/rmdopen-2024-004317

M3 - Journal article

C2 - 39242113

AN - SCOPUS:85203610522

SN - 2056-5933

VL - 10

JO - RMD Open

JF - RMD Open

IS - 3

M1 - e004317

ER -

Inflammatory biomarkers predicting long-term remission and active disease in juvenile idiopathic arthritis: a population-based study of the Nordic JIA cohort

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