A Biomarker of Type VI Collagen Degradation (C6M) Is Associated with Changes in ASDAS MRI Measures of Inflammation in Patients with Axial Spondyloarthritis During TNF Inhibitor Therapy

Signe Holm Nielsen¹, Anne Bay-Jensen ², Mikkel Østergaard ³, Anne Siebuhr ⁴, Morten Karsdal ⁵, inge Juul Sørensen ⁶, Ulrich Weber ⁷, Anne Gitte Loft ⁸, Gina Kollerup ⁹, Gorm Thamsborg ⁹, Ole Rintek Madsen ¹⁰, Jakob Møller ¹¹ and Susanne Juhl Pedersen ¹², ¹Nordic Bioscience/Technical University of Denmark, Herlev, Denmark, ²Nordic Bioscience, Herlev, Denmark, ³Copenhagen Center for Arthritis Research, University of Copenhagen, Copenhagen, Denmark, ⁴Nordic Bioscience, Herlev, ⁵Nordic Bioscience, Copenhagen, Denmark, ⁶Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Rigshospitalet, Glostrup, Denmark, Glostrup, Denmark, ⁷Danish Hospital for Rheumatic Diseases, University Hospital of Southern Denmark, Sonderborg, Denmark, ⁸Department of Rheumatology, Aarhus University Hospital, Aarhus, Denmark, Århus, Denmark, ⁹Center for Rheumatology and Spine Diseases, Rigshospitalet, Copenhagen, Denmark, Copenhagen, Hovedstaden, Denmark, ¹⁰Center for Rheumatology and Spine Diseases, Rigshospitalet, Copenhagen, Denmark, Copenhagen, Denmark, ¹¹Department of Radiology, Herlev and Gentofte University Hospital, Herlev, Denmark, Copenhagen, Denmark, ¹²Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Rigshospitalet, Copenhagen, Denmark, Copenhagen, Hovedstaden, Denmark

Meeting: 2019 ACR/ARP Annual Meeting

Keywords: Ankylosing spondylitis (AS), Biomarkers, collagen and anti-TNF therapy, extracellular matrix proteins

Session Information

Date: Sunday, November 10, 2019

Title: Spondyloarthritis Including Psoriatic Arthritis – Clinical Poster I: Axial Spondyloarthritis, Clinical Features

Session Type: Poster Session (Sunday)

Session Time: 9:00AM-11:00AM

Background/Purpose: Axial spondyloarthritis (AxSpa) is characterized by inflammation in the sacroiliac joints and spine and associated with extracellular matrix (ECM) remodelling of affected tissues. Type VI collagen (COL6) is an ECM protein located in the interface between the basement membrane and interstitial matrix, where is binds to other ECM proteins and support cell-cell interactions. C6M is a metabolite of COL6 that is released from the inflamed tissue and can be measured in serum as a biomarker of tissue remodelling. The aim of this study was to investigate the association of C6M in patients with AxSpA, and its relationship with treatment of TNF-α inhibitors for 46 weeks in the prospective Biomarkers in Spondyloarthritis (BIOSPA) study.

Methods: C6M was measured in serum from the BIOSPA study (n=55) at baseline, week 2, 22, 46 after treatment with TNF-inhibitors (infliximab, etanercept or adalimumab). Differences between the biomarker levels at the four different timepoints were calculated using repeated measures ANOVA. A t-test was used to calculate the improvement is ASDAS, while Spearman correlations were performed to explore the association of C6M and MRI measures.

Results: Patients included were 82% males, with median age of 40 years (IQR: 32-48), and 84% were human leucocyte antigen-B27 positive. They had a median disease duration of 5.5 years (IQR: 2-10), and a median baseline level of ASDAS 3.9 (IQR: 3.0-4.5). The levels of C6M can be found in Table 1. Levels of C6M were significantly decreased after 2 and 22 weeks of treatment compared to baseline (p=0.0014 and p=0.0015, respectively). C6M was significantly decreased in patients with clinical important improvement after 22 weeks (ASDAS ≥Δ1.1) (p=0.010) and major improvement after 22 and 46 weeks (ASDAS ≥Δ2.0) (p=0.0002 and p=0.018, respectively) as shown in Table 2 and 3. Baseline and week 22 levels of C6M correlated to the total SPARCC Spine and Sacroiliac Joint Inflammation score measured by MRI (Spearmans Rho=0.496, p< 0.001 and Spearmans Rho=0.297, p=0.031 respectively).

Conclusion: The biomarker C6M was associated with changes in ASDAS and MRI measures of inflammation during TNF-inhibitor treatment. This indicates that C6M may be a tissue-based marker of disease activity.

Table 1

Table 1. Levels of C6M

Table 2

Table 2. C6M in relation to changes in ASDAS from baseline to week 22.

Table 3

Table 3. C6M in relation to changes in ASDAS from baseline to week 46.

Disclosure: S. Holm Nielsen, Nordic Bioscience, 3; A. Bay-Jensen, Nordic Bioscience, 1, 2, 3; M. Østergaard, AbbVie, 2, 8, 9, Abbvie, 2, 5, 8, Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli Lilly, Hospira, Janssen, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, UCB, 5, 8, Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli-Lilly, Hospira, Janssen, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, and UCB, 5, 8, Abbvie, Celgene, Centocor, Merck, and Novartis, 2, Abbvie, Celgene, Centocor, Merck, Novartis, 2, BMS, 2, 5, 8, 9, Boehringer Ingelheim, 5, 8, Boehringer-Ingelheim, 2, 8, Boehringer-ingelheim, 9, Celgene, 2, 5, 8, Centocor, 2, Eli Lilly, 5, 8, 9, Eli Lilly and Company, 5, 8, Eli-Lilly, 2, 8, Hospira, 2, 5, 8, Janssen, 2, 5, 8, 9, Merck, 2, 5, 8, 9, Novartis, 2, 5, 8, Novo, 2, 5, 8, Novo Nordisk, 5, 8, Orion, 2, 5, 8, Pfizer, 2, 5, 8, 9, Regeneron, 2, 5, 8, Roche, 2, 5, 8, roche, 9, Sandoz, 2, 8, Sanofi, 2, 8, UCB, 2, 5, 8; A. Siebuhr, Nordic Bioscience, 3; M. Karsdal, Nordic Biosceince, 1, 3, Nordic Bioscience, 1, 2, 3, 4, 5; i. Sørensen, None; U. Weber, None; A. Loft, None; G. Kollerup, None; G. Thamsborg, None; O. Rintek Madsen, None; J. Møller, None; S. Juhl Pedersen, None.

To cite this abstract in AMA style:

Holm Nielsen S, Bay-Jensen A, Østergaard M, Siebuhr A, Karsdal M, Sørensen i, Weber U, Loft A, Kollerup G, Thamsborg G, Rintek Madsen O, Møller J, Juhl Pedersen S. A Biomarker of Type VI Collagen Degradation (C6M) Is Associated with Changes in ASDAS MRI Measures of Inflammation in Patients with Axial Spondyloarthritis During TNF Inhibitor Therapy [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/a-biomarker-of-type-vi-collagen-degradation-c6m-is-associated-with-changes-in-asdas-mri-measures-of-inflammation-in-patients-with-axial-spondyloarthritis-during-tnf-inhibitor-therapy/. Accessed .

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