RT Journal Article
SR Electronic
T1 Identification of patient endotypes and adalimumab treatment responders in axial spondyloarthritis using blood-derived extracellular matrix biomarkers
JF RMD Open
JO RMD Open
FD EULAR
SP e003769
DO 10.1136/rmdopen-2023-003769
VO 10
IS 1
A1 Port, Helena
A1 Christiansen, Frederik
A1 Nielsen, Signe Holm
A1 Frederiksen, Peder
A1 Bay-Jensen, Anne-C
A1 Karsdal, Morten Asser
A1 Seven, Sengul
A1 Sørensen, Inge Juul
A1 Loft, Anne Gitte
A1 Madsen, Ole Rintek
A1 Ostergaard, Mikkel
A1 Pedersen, Susanne J
YR 2024
UL http://rmdopen.bmj.com/content/10/1/e003769.abstract
AB Objective To explore the potential of a panel of ECM remodelling markers as endotyping tools for axial spondyloarthritis (axSpA) by separating patients into subtypes and investigate how they differ among each other in disease activity scores and response to treatment with adalimumab.Methods In three axSpA studies, a panel of 14 blood-based ECM biomarkers related to formation of collagen (PRO-C2, PRO-C3, PRO-C6), degradation of collagen by metalloproteinases (C1M, C2M, T2CM, C3M, C4M, C6M, C10C), matrix metalloproteinase (MMP)-degraded prolargin (PROM), MMP-degraded and citrullinated vimentin (VICM), basement membrane turnover (PRO-C4) and neutrophil activity (CPa9-HNE) were assessed to enable patient clustering (endotyping). MASH (n=41) was a cross-sectional study, while Adalimumab in Axial Spondyloarthritis study (ASIM,n=45) and Danish Multicenter Study of Adalimumab in Spondyloarthritis (DANISH, n=49) were randomised, double-blind placebo-controlled trials of adalimumab versus placebo every other week for 6 or 12 weeks, respectively, followed by active treatment. Biomarker data were log-transformed, standardised by mean centering and scaled by the SD prior to principal component analysis and K-means clustering.Results Based on all three studies, we identified two orthogonal dimensions reflecting: (1) inflammation and neutrophil activity (driven by C1M and CPa9-HNE) and (2) collagen turnover (driven by PRO-C2). Three endotypes were identified: high inflammation endotype (Endotype1), low inflammation endotype (Endotype 2) and high collagen turnover endotype (Endotype3). Endotype1 showed higher disease activity (Ankylosing Spondylitis Disease Activity Score (ASDAS)) at baseline compared with Endotype2 and Endotype3 and higher percentage of patients responding to adalimumab based on ASDAS clinical improvement at week 24. Endotype3 showed higher percentage of patients with 50% improvement in Bath Ankylosing Spondylitis Disease Activity Index response at week 24 compared with Endotype2.Conclusion These endotypes differ in their tissue remodelling profile and may in the future have utility for patient stratification and treatment tailoring.