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

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.

• Authors: 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
• Journal: Arthritis research & therapy (Arthritis Res Ther) Vol. 25 Issue 1 Pg. 157 (08 25 2023) ISSN: 1478-6362 [Electronic] England
• PMID: 37626399 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2023. BioMed Central Ltd., part of Springer Nature.

Chemical References

• Adalimumab
• C-Reactive Protein
• Tumor Necrosis Factor-alpha
• Biomarkers
• Complement C4
• Tumor Necrosis Factor Inhibitors

Topics

• 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