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

Helena Port*, Signe Holm Nielsen, Peder Frederiksen, Sofie Falkenløve Madsen, Anne-Christine Bay-Jensen, Inge Juul Sørensen, Bente Jensen, Anne Gitte Loft, Ole Rintek Madsen, Mikkel Østergaard, Susanne Juhl Pedersen

*Corresponding author for this work
1 Citation (Scopus)

Abstract

OBJECTIVE: To 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).

METHODS: We 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.

RESULTS: C1M, 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.

CONCLUSION: ECM metabolites showed a pharmacodynamic effect and were associated with ASDAS response during TNF-α inhibitor treatment in patients with axSpA.

Original languageEnglish
Article number157
JournalArthritis Research & Therapy
Volume25
Issue number1
ISSN1478-6354
DOIs
Publication statusPublished - 25 Aug 2023

Keywords

  • Humans
  • Adalimumab/therapeutic use
  • C-Reactive Protein
  • Tumor Necrosis Factor-alpha
  • Randomized Controlled Trials as Topic
  • Biomarkers
  • Complement C4
  • Extracellular Matrix
  • Tumor Necrosis Factor Inhibitors
  • Axial Spondyloarthritis
  • Axial spondyloarthritis
  • Extracellular matrix
  • Adalimumab

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