Extracellular matrix turnover biomarkers reflect pharmacodynamic effects and treatment response of adalimumab in patients with axial spondyloarthritis—results from two randomized controlled trials

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Standard

Extracellular matrix turnover biomarkers reflect pharmacodynamic effects and treatment response of adalimumab in patients with axial spondyloarthritis—results from two randomized controlled trials. / Port I Linares, Helena; Holm Nielsen, Signe; Frederiksen, Peder; Madsen, Sofie Falkenløve; Bay-Jensen, Anne-Christine; Sørensen, Inge Juul; Jensen, Bente; Loft, Anne Gitte; gjc556, gjc556; Østergaard, Mikkel; Pedersen, Susanne Juhl.

I: Arthritis Research & Therapy, Bind 25, 157, 2023.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Port I Linares, H, Holm Nielsen, S, Frederiksen, P, Madsen, SF, Bay-Jensen, A-C, Sørensen, IJ, Jensen, B, Loft, AG, gjc556, G, Østergaard, M & Pedersen, SJ 2023, 'Extracellular matrix turnover biomarkers reflect pharmacodynamic effects and treatment response of adalimumab in patients with axial spondyloarthritis—results from two randomized controlled trials', Arthritis Research & Therapy, bind 25, 157. https://doi.org/10.1186/s13075-023-03132-5

APA

Port I Linares, H., Holm Nielsen, S., Frederiksen, P., Madsen, S. F., Bay-Jensen, A-C., Sørensen, I. J., Jensen, B., Loft, A. G., gjc556, G., Østergaard, M., & Pedersen, S. J. (2023). Extracellular matrix turnover biomarkers reflect pharmacodynamic effects and treatment response of adalimumab in patients with axial spondyloarthritis—results from two randomized controlled trials. Arthritis Research & Therapy, 25, [157]. https://doi.org/10.1186/s13075-023-03132-5

Vancouver

Port I Linares H, Holm Nielsen S, Frederiksen P, Madsen SF, Bay-Jensen A-C, Sørensen IJ o.a. Extracellular matrix turnover biomarkers reflect pharmacodynamic effects and treatment response of adalimumab in patients with axial spondyloarthritis—results from two randomized controlled trials. Arthritis Research & Therapy. 2023;25. 157. https://doi.org/10.1186/s13075-023-03132-5

Author

Port I Linares, Helena ; Holm Nielsen, Signe ; Frederiksen, Peder ; Madsen, Sofie Falkenløve ; Bay-Jensen, Anne-Christine ; Sørensen, Inge Juul ; Jensen, Bente ; Loft, Anne Gitte ; gjc556, gjc556 ; Østergaard, Mikkel ; Pedersen, Susanne Juhl. / Extracellular matrix turnover biomarkers reflect pharmacodynamic effects and treatment response of adalimumab in patients with axial spondyloarthritis—results from two randomized controlled trials. I: Arthritis Research & Therapy. 2023 ; Bind 25.

Bibtex

@article{801bba0c0c6040b6808893b8646325a6,
title = "Extracellular matrix turnover biomarkers reflect pharmacodynamic effects and treatment response of adalimumab in patients with axial spondyloarthritis—results from two randomized controlled trials",
abstract = "ObjectiveTo investigate if extracellular matrix (ECM) blood-based biomarkers reflect the pharmacodynamic effect and response to TNF-α inhibitor therapy (adalimumab, ADA), in patients with axial spondyloarthritis (axSpA).MethodsWe investigated ECM biomarkers in two randomized, double-blind, placebo-controlled trials of axSpA patients (DANISH and ASIM, n = 52 and n = 49, respectively) receiving ADA 40 mg or placebo every other week for 12 and 6 weeks, respectively, and thereafter ADA to week 48. Serum concentrations of degraded type I (C1M), II (C2M, T2CM), III (C3M), IV (C4M), VI (C6M), type X (C10C) collagen; metabolite of C-reactive protein (CRPM), prolargin (PROM), citrullinated vimentin (VICM), calprotectin (CPa9-HNE); and formation of type II (PRO‑C2), III (PRO‑C3), and VI (PRO‑C6) turnover of type IV collagen (PRO-C4) were measured at baseline and weeks 6 or 12, 24, and 48. The pharmacodynamic effect and treatment response to ADA was evaluated by linear mixed models, and correlations between biomarkers and clinical scores were assessed by Spearman{\textquoteright}s correlation.ResultsC1M, C3M, C4M, C6M, CRP, PRO-C4, and CPa9-HNE levels declined after 6 or 12 weeks in patients receiving ADA compared to placebo (all p < 0.05). Patients with AS Disease Activity Score C-reactive protein (ASDAS CRP) major improvement and/or clinically important improvement had significantly higher C1M, C3M, C4M, C6M, and PRO-C4 levels than patients with no/low improvement at baseline (all p < 0.05). Baseline levels of biomarkers showed weak to moderate correlations with ASDAS and structural damage scores.ConclusionECM metabolites showed a pharmacodynamic effect and were associated with ASDAS response during TNF-α inhibitor treatment in patients with axSpA.",
author = "{Port I Linares}, Helena and {Holm Nielsen}, Signe and Peder Frederiksen and Madsen, {Sofie Falkenl{\o}ve} and Anne-Christine Bay-Jensen and S{\o}rensen, {Inge Juul} and Bente Jensen and Loft, {Anne Gitte} and gjc556 gjc556 and Mikkel {\O}stergaard and Pedersen, {Susanne Juhl}",
year = "2023",
doi = "10.1186/s13075-023-03132-5",
language = "English",
volume = "25",
journal = "Arthritis Research & Therapy",
issn = "1478-6354",
publisher = "BioMed Central",

}

RIS

TY - JOUR

T1 - Extracellular matrix turnover biomarkers reflect pharmacodynamic effects and treatment response of adalimumab in patients with axial spondyloarthritis—results from two randomized controlled trials

AU - Port I Linares, Helena

AU - Holm Nielsen, Signe

AU - Frederiksen, Peder

AU - Madsen, Sofie Falkenløve

AU - Bay-Jensen, Anne-Christine

AU - Sørensen, Inge Juul

AU - Jensen, Bente

AU - Loft, Anne Gitte

AU - gjc556, gjc556

AU - Østergaard, Mikkel

AU - Pedersen, Susanne Juhl

PY - 2023

Y1 - 2023

N2 - ObjectiveTo investigate if extracellular matrix (ECM) blood-based biomarkers reflect the pharmacodynamic effect and response to TNF-α inhibitor therapy (adalimumab, ADA), in patients with axial spondyloarthritis (axSpA).MethodsWe investigated ECM biomarkers in two randomized, double-blind, placebo-controlled trials of axSpA patients (DANISH and ASIM, n = 52 and n = 49, respectively) receiving ADA 40 mg or placebo every other week for 12 and 6 weeks, respectively, and thereafter ADA to week 48. Serum concentrations of degraded type I (C1M), II (C2M, T2CM), III (C3M), IV (C4M), VI (C6M), type X (C10C) collagen; metabolite of C-reactive protein (CRPM), prolargin (PROM), citrullinated vimentin (VICM), calprotectin (CPa9-HNE); and formation of type II (PRO‑C2), III (PRO‑C3), and VI (PRO‑C6) turnover of type IV collagen (PRO-C4) were measured at baseline and weeks 6 or 12, 24, and 48. The pharmacodynamic effect and treatment response to ADA was evaluated by linear mixed models, and correlations between biomarkers and clinical scores were assessed by Spearman’s correlation.ResultsC1M, C3M, C4M, C6M, CRP, PRO-C4, and CPa9-HNE levels declined after 6 or 12 weeks in patients receiving ADA compared to placebo (all p < 0.05). Patients with AS Disease Activity Score C-reactive protein (ASDAS CRP) major improvement and/or clinically important improvement had significantly higher C1M, C3M, C4M, C6M, and PRO-C4 levels than patients with no/low improvement at baseline (all p < 0.05). Baseline levels of biomarkers showed weak to moderate correlations with ASDAS and structural damage scores.ConclusionECM metabolites showed a pharmacodynamic effect and were associated with ASDAS response during TNF-α inhibitor treatment in patients with axSpA.

AB - ObjectiveTo investigate if extracellular matrix (ECM) blood-based biomarkers reflect the pharmacodynamic effect and response to TNF-α inhibitor therapy (adalimumab, ADA), in patients with axial spondyloarthritis (axSpA).MethodsWe investigated ECM biomarkers in two randomized, double-blind, placebo-controlled trials of axSpA patients (DANISH and ASIM, n = 52 and n = 49, respectively) receiving ADA 40 mg or placebo every other week for 12 and 6 weeks, respectively, and thereafter ADA to week 48. Serum concentrations of degraded type I (C1M), II (C2M, T2CM), III (C3M), IV (C4M), VI (C6M), type X (C10C) collagen; metabolite of C-reactive protein (CRPM), prolargin (PROM), citrullinated vimentin (VICM), calprotectin (CPa9-HNE); and formation of type II (PRO‑C2), III (PRO‑C3), and VI (PRO‑C6) turnover of type IV collagen (PRO-C4) were measured at baseline and weeks 6 or 12, 24, and 48. The pharmacodynamic effect and treatment response to ADA was evaluated by linear mixed models, and correlations between biomarkers and clinical scores were assessed by Spearman’s correlation.ResultsC1M, C3M, C4M, C6M, CRP, PRO-C4, and CPa9-HNE levels declined after 6 or 12 weeks in patients receiving ADA compared to placebo (all p < 0.05). Patients with AS Disease Activity Score C-reactive protein (ASDAS CRP) major improvement and/or clinically important improvement had significantly higher C1M, C3M, C4M, C6M, and PRO-C4 levels than patients with no/low improvement at baseline (all p < 0.05). Baseline levels of biomarkers showed weak to moderate correlations with ASDAS and structural damage scores.ConclusionECM metabolites showed a pharmacodynamic effect and were associated with ASDAS response during TNF-α inhibitor treatment in patients with axSpA.

U2 - 10.1186/s13075-023-03132-5

DO - 10.1186/s13075-023-03132-5

M3 - Journal article

C2 - 37626399

VL - 25

JO - Arthritis Research & Therapy

JF - Arthritis Research & Therapy

SN - 1478-6354

M1 - 157

ER -

ID: 364546068