Levels of extracellular matrix metabolites are associated with changes in Ankylosing Spondylitis Disease Activity Score and MRI inflammation scores in patients with axial spondyloarthritis during TNF inhibitor therapy
Abstract Background/purpose In axial spondyloarthritis (axSpA) inflammation of the sacroiliac joints and spine is associated with local extracellular matrix (ECM) remodeling of affected tissues. We aimed to investigate the association of ECM metabolites with treatment response in axSpA patients trea...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2022-12-01
|
| Series: | Arthritis Research & Therapy |
| Online Access: | https://doi.org/10.1186/s13075-022-02967-8 |
| _version_ | 1797977368337317888 |
|---|---|
| author | Signe Holm Nielsen Shu Sun Anne C. Bay-Jensen Morten Karsdal Inge Juul Sørensen Ulrich Weber Anne Gitte Loft Gina Kollerup Gorm Thamsborg Ole Rintek Madsen Jakob Møller Mikkel Østergaard Susanne Juhl Pedersen |
| author_facet | Signe Holm Nielsen Shu Sun Anne C. Bay-Jensen Morten Karsdal Inge Juul Sørensen Ulrich Weber Anne Gitte Loft Gina Kollerup Gorm Thamsborg Ole Rintek Madsen Jakob Møller Mikkel Østergaard Susanne Juhl Pedersen |
| author_sort | Signe Holm Nielsen |
| collection | DOAJ |
| description | Abstract Background/purpose In axial spondyloarthritis (axSpA) inflammation of the sacroiliac joints and spine is associated with local extracellular matrix (ECM) remodeling of affected tissues. We aimed to investigate the association of ECM metabolites with treatment response in axSpA patients treated with TNF-α inhibitory therapy for 46 weeks. Methods In a prospective clinical study of axSpA patients (n=55) initiating a TNF inhibitor (infliximab, etanercept, or adalimumab), serum concentrations of formation of type I (PRO-C1), type III (PRO-C3), and type VI (PRO-C6) collagen; turnover of type IV collagen (PRO-C4), and matrix-metalloproteinase (MMP)-degraded type III (C3M) collagen, MMP-degraded type IV (C4M), type VI (C6M), and type VII (C7M) collagen, and cathepsin-degraded type X collagen (C10C), MMP-mediated metabolite of C-reactive protein (CRPM), citrullinated vimentin (VICM), and neutrophil elastase-degraded elastin (EL-NE) were measured at baseline, week 2, week 22, and week 46. Results Patients were mostly males (82%), HLA-B27 positive (84%), with a median age of 40 years (IQR: 32–48), disease duration of 5.5 years (IQR: 2–10), and a baseline Ankylosing Spondylitis Disease Activity Score (ASDAS) of 3.9 (IQR: 3.0–4.5). Compared to baseline, PRO-C1 levels were significantly increased after two weeks of treatment, C6M levels were significantly decreased after two and 22 weeks (repeated measures ANOVA, p=0.0014 and p=0.0015, respectively), EL-NE levels were significantly decreased after 2 weeks (p=0.0008), VICM levels were significantly decreased after two and 22 weeks (p=0.0163 and p=0.0374, respectively), and CRP were significantly decreased after two and 22 weeks (both p=0.0001). Baseline levels of PRO-C1, PRO-C3, C6M, VICM, and CRP were all associated with ASDAS clinically important and major improvement after 22 weeks (ΔASDAS ≥1.1) (Mann–Whitney test, p=0.006, p=0.008, p<0.001, <0.001, <0.001, respectively), while C6M, VICM and CRP levels were associated with ASDAS clinically important and major improvement after 46 weeks (ΔASDAS ≥2.0) (p=0.002, p=0.044, and p<0.001, respectively). PRO-C1 and C6M levels were associated with a Bath AS Disease Activity Score (BASDAI) response to TNF-inhibitory therapy after 22 weeks (Mann–Whitney test, p=0.020 and p=0.049, respectively). Baseline levels of PRO-C4 and C6M were correlated with the total SPARCC MRI Spine and Sacroiliac Joint Inflammation score (Spearman’s Rho ρ=0.279, p=0.043 and ρ=0.496, p=0.0002, respectively). Conclusions Extracellular matrix metabolites were associated with ASDAS response, MRI inflammation, and clinical treatment response during TNF-inhibitory treatment in patients with axSpA. |
| first_indexed | 2024-04-11T05:05:44Z |
| format | Article |
| id | doaj.art-d418a3f4babb4d4ba9b8a17bd2d5c1a6 |
| institution | Directory Open Access Journal |
| issn | 1478-6362 |
| language | English |
| last_indexed | 2024-04-11T05:05:44Z |
| publishDate | 2022-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Arthritis Research & Therapy |
| spelling | doaj.art-d418a3f4babb4d4ba9b8a17bd2d5c1a62022-12-25T12:24:24ZengBMCArthritis Research & Therapy1478-63622022-12-0124111010.1186/s13075-022-02967-8Levels of extracellular matrix metabolites are associated with changes in Ankylosing Spondylitis Disease Activity Score and MRI inflammation scores in patients with axial spondyloarthritis during TNF inhibitor therapySigne Holm Nielsen0Shu Sun1Anne C. Bay-Jensen2Morten Karsdal3Inge Juul Sørensen4Ulrich Weber5Anne Gitte Loft6Gina Kollerup7Gorm Thamsborg8Ole Rintek Madsen9Jakob Møller10Mikkel Østergaard11Susanne Juhl Pedersen12Nordic BioscienceNordic BioscienceNordic BioscienceNordic BioscienceCopenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, RigshospitaletDanish Hospital for Rheumatic Diseases, University Hospital of Southern DenmarkDepartments of Rheumatology, Hospital LillebæltCopenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, RigshospitaletCopenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, RigshospitaletCopenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, RigshospitaletDepartment of Radiology, Herlev HospitalCopenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, RigshospitaletCopenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, RigshospitaletAbstract Background/purpose In axial spondyloarthritis (axSpA) inflammation of the sacroiliac joints and spine is associated with local extracellular matrix (ECM) remodeling of affected tissues. We aimed to investigate the association of ECM metabolites with treatment response in axSpA patients treated with TNF-α inhibitory therapy for 46 weeks. Methods In a prospective clinical study of axSpA patients (n=55) initiating a TNF inhibitor (infliximab, etanercept, or adalimumab), serum concentrations of formation of type I (PRO-C1), type III (PRO-C3), and type VI (PRO-C6) collagen; turnover of type IV collagen (PRO-C4), and matrix-metalloproteinase (MMP)-degraded type III (C3M) collagen, MMP-degraded type IV (C4M), type VI (C6M), and type VII (C7M) collagen, and cathepsin-degraded type X collagen (C10C), MMP-mediated metabolite of C-reactive protein (CRPM), citrullinated vimentin (VICM), and neutrophil elastase-degraded elastin (EL-NE) were measured at baseline, week 2, week 22, and week 46. Results Patients were mostly males (82%), HLA-B27 positive (84%), with a median age of 40 years (IQR: 32–48), disease duration of 5.5 years (IQR: 2–10), and a baseline Ankylosing Spondylitis Disease Activity Score (ASDAS) of 3.9 (IQR: 3.0–4.5). Compared to baseline, PRO-C1 levels were significantly increased after two weeks of treatment, C6M levels were significantly decreased after two and 22 weeks (repeated measures ANOVA, p=0.0014 and p=0.0015, respectively), EL-NE levels were significantly decreased after 2 weeks (p=0.0008), VICM levels were significantly decreased after two and 22 weeks (p=0.0163 and p=0.0374, respectively), and CRP were significantly decreased after two and 22 weeks (both p=0.0001). Baseline levels of PRO-C1, PRO-C3, C6M, VICM, and CRP were all associated with ASDAS clinically important and major improvement after 22 weeks (ΔASDAS ≥1.1) (Mann–Whitney test, p=0.006, p=0.008, p<0.001, <0.001, <0.001, respectively), while C6M, VICM and CRP levels were associated with ASDAS clinically important and major improvement after 46 weeks (ΔASDAS ≥2.0) (p=0.002, p=0.044, and p<0.001, respectively). PRO-C1 and C6M levels were associated with a Bath AS Disease Activity Score (BASDAI) response to TNF-inhibitory therapy after 22 weeks (Mann–Whitney test, p=0.020 and p=0.049, respectively). Baseline levels of PRO-C4 and C6M were correlated with the total SPARCC MRI Spine and Sacroiliac Joint Inflammation score (Spearman’s Rho ρ=0.279, p=0.043 and ρ=0.496, p=0.0002, respectively). Conclusions Extracellular matrix metabolites were associated with ASDAS response, MRI inflammation, and clinical treatment response during TNF-inhibitory treatment in patients with axSpA.https://doi.org/10.1186/s13075-022-02967-8 |
| spellingShingle | Signe Holm Nielsen Shu Sun Anne C. Bay-Jensen Morten Karsdal Inge Juul Sørensen Ulrich Weber Anne Gitte Loft Gina Kollerup Gorm Thamsborg Ole Rintek Madsen Jakob Møller Mikkel Østergaard Susanne Juhl Pedersen Levels of extracellular matrix metabolites are associated with changes in Ankylosing Spondylitis Disease Activity Score and MRI inflammation scores in patients with axial spondyloarthritis during TNF inhibitor therapy Arthritis Research & Therapy |
| title | Levels of extracellular matrix metabolites are associated with changes in Ankylosing Spondylitis Disease Activity Score and MRI inflammation scores in patients with axial spondyloarthritis during TNF inhibitor therapy |
| title_full | Levels of extracellular matrix metabolites are associated with changes in Ankylosing Spondylitis Disease Activity Score and MRI inflammation scores in patients with axial spondyloarthritis during TNF inhibitor therapy |
| title_fullStr | Levels of extracellular matrix metabolites are associated with changes in Ankylosing Spondylitis Disease Activity Score and MRI inflammation scores in patients with axial spondyloarthritis during TNF inhibitor therapy |
| title_full_unstemmed | Levels of extracellular matrix metabolites are associated with changes in Ankylosing Spondylitis Disease Activity Score and MRI inflammation scores in patients with axial spondyloarthritis during TNF inhibitor therapy |
| title_short | Levels of extracellular matrix metabolites are associated with changes in Ankylosing Spondylitis Disease Activity Score and MRI inflammation scores in patients with axial spondyloarthritis during TNF inhibitor therapy |
| title_sort | levels of extracellular matrix metabolites are associated with changes in ankylosing spondylitis disease activity score and mri inflammation scores in patients with axial spondyloarthritis during tnf inhibitor therapy |
| url | https://doi.org/10.1186/s13075-022-02967-8 |
| work_keys_str_mv | AT signeholmnielsen levelsofextracellularmatrixmetabolitesareassociatedwithchangesinankylosingspondylitisdiseaseactivityscoreandmriinflammationscoresinpatientswithaxialspondyloarthritisduringtnfinhibitortherapy AT shusun levelsofextracellularmatrixmetabolitesareassociatedwithchangesinankylosingspondylitisdiseaseactivityscoreandmriinflammationscoresinpatientswithaxialspondyloarthritisduringtnfinhibitortherapy AT annecbayjensen levelsofextracellularmatrixmetabolitesareassociatedwithchangesinankylosingspondylitisdiseaseactivityscoreandmriinflammationscoresinpatientswithaxialspondyloarthritisduringtnfinhibitortherapy AT mortenkarsdal levelsofextracellularmatrixmetabolitesareassociatedwithchangesinankylosingspondylitisdiseaseactivityscoreandmriinflammationscoresinpatientswithaxialspondyloarthritisduringtnfinhibitortherapy AT ingejuulsørensen levelsofextracellularmatrixmetabolitesareassociatedwithchangesinankylosingspondylitisdiseaseactivityscoreandmriinflammationscoresinpatientswithaxialspondyloarthritisduringtnfinhibitortherapy AT ulrichweber levelsofextracellularmatrixmetabolitesareassociatedwithchangesinankylosingspondylitisdiseaseactivityscoreandmriinflammationscoresinpatientswithaxialspondyloarthritisduringtnfinhibitortherapy AT annegitteloft levelsofextracellularmatrixmetabolitesareassociatedwithchangesinankylosingspondylitisdiseaseactivityscoreandmriinflammationscoresinpatientswithaxialspondyloarthritisduringtnfinhibitortherapy AT ginakollerup levelsofextracellularmatrixmetabolitesareassociatedwithchangesinankylosingspondylitisdiseaseactivityscoreandmriinflammationscoresinpatientswithaxialspondyloarthritisduringtnfinhibitortherapy AT gormthamsborg levelsofextracellularmatrixmetabolitesareassociatedwithchangesinankylosingspondylitisdiseaseactivityscoreandmriinflammationscoresinpatientswithaxialspondyloarthritisduringtnfinhibitortherapy AT olerintekmadsen levelsofextracellularmatrixmetabolitesareassociatedwithchangesinankylosingspondylitisdiseaseactivityscoreandmriinflammationscoresinpatientswithaxialspondyloarthritisduringtnfinhibitortherapy AT jakobmøller levelsofextracellularmatrixmetabolitesareassociatedwithchangesinankylosingspondylitisdiseaseactivityscoreandmriinflammationscoresinpatientswithaxialspondyloarthritisduringtnfinhibitortherapy AT mikkeløstergaard levelsofextracellularmatrixmetabolitesareassociatedwithchangesinankylosingspondylitisdiseaseactivityscoreandmriinflammationscoresinpatientswithaxialspondyloarthritisduringtnfinhibitortherapy AT susannejuhlpedersen levelsofextracellularmatrixmetabolitesareassociatedwithchangesinankylosingspondylitisdiseaseactivityscoreandmriinflammationscoresinpatientswithaxialspondyloarthritisduringtnfinhibitortherapy |