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

Autor: 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
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Arthritis Research & Therapy, Vol 25, Iss 1, Pp 1-14 (2023)
Druh dokumentu: article
ISSN: 1478-6362
DOI: 10.1186/s13075-023-03132-5
Popis: 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
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