Rheumatology, Osteoarthritis, Rheumatoid Arthritis
24. Jul 2019
Identification of pathological RA endotypes using blood-based biomarkers reflecting tissue metabolism. A retrospective and explorative analysis of two phase III RA studies.
There is an increasing demand for accurate endotyping of patients according to their pathogenesis to allow more targeted treatment. We explore a combination of blood-based joint tissue metabolites (neoepitopes) to enable patient clustering through distinct disease profiles. We analysed data from two…
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Journal:
Authors:
- Blair JPM,
- Bager C,
- Karsdal MA,
- Bay-Jensen AC,
Rheumatology, Rheumatoid Arthritis, Bone
22. Feb 2019
Combining Naproxen and a Dual Amylin and Calcitonin Receptor Agonist improves pain and structural outcomes in the Collagen-Induced Arthritis rat model
BACKGROUND:
Pain is a debilitating symptom of rheumatoid arthritis (RA), caused by joint inflammation and cartilage and bone destruction. Nonsteroidal anti-inflammatory drugs (NSAIDs) are used to treat pain and inflammation in RA, but are not disease-modifying and do not prevent joint destruction w…
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Journal:
Authors:
- Katri A,
- Dabrowska A,
- Löfvall H,
- Ding M,
- Karsdal MA,
- Andreassen KV,
- Schneider Thudium C,
- Henriksen K,
Rheumatology, Osteoarthritis, Rheumatoid Arthritis
14. Jan 2019
Potential diagnostic value of a type X collagen neo-epitope biomarker for knee osteoarthritis.
OBJECTIVE:
Phenotypic changes of chondrocytes toward hypertrophy might be fundamental in the pathogenesis of OA, of which type X collagen (Col10) is a well-known marker. The purpose was to develop a specific immunoassay for blood quantification of a newly identified neo-epitope of type X collagen t…
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Journal:
Authors:
- He Y,
- Manon-Jensen T,
- Arendt-Nielsen L,
- Petersen KK,
- Christiansen T,
- Samuels J,
- Abramson S,
- Karsdal MA,
- Attur M,
- Bay-Jensen AC,
Rheumatology, Rheumatoid Arthritis
7. Nov 2018
The VICM biomarker is released from activated macrophages and inhibited by anti-GM-CSFRα-mAb treatment in rheumatoid arthritis patients.
OBJECTIVES:
Macrophages possess widespread pro-inflammatory, destructive, and remodelling capabilities that can critically contribute to acute and chronic diseases, such as rheumatoid arthritis (RA). Continuous monitoring and measurement of selective counteraction of macrophage activity in patients…
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Journal:
Authors:
- Mortensen JH,
- Guo X,
- De Los Reyes M,
- Dziegiel MH,
- Bay Jensen AC,
- White WI,
Rheumatology, Rheumatoid Arthritis
8. May 2018
Type IV collagen metabolism is associated with disease activity, radiographic progression and response to tocilizumab in rheumatoid arthritis
OBJECTIVES:
The expanding spectrum of targeted therapies for rheumatoid arthritis (RA) implies a need for development of precision tools for disease assessment reflecting pathobiologic processes. Type IV collagen is an abundant protein of basement membranes, but is also present in the intercellular…
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Journal:
Authors:
- Gudmann NS,
- Junker P,
- Juhl P,
- Thudium CS,
- Siebuhr AS,
- Byrjalsen I,
- Karsdal MA,
- Bay-Jensen AC,
Rheumatology, Rheumatoid Arthritis
18. Apr 2018
Translational Biomarkers and Ex Vivo Models of Joint Tissues as a Tool for Drug Development in Rheumatoid Arthritis
OBJECTIVE:
Rheumatoid arthritis (RA) is a chronic, autoimmune and degenerative joint disease leading to disability, reduced life quality, and increased mortality. Although several synthetic and biological disease modifying anti-rheumatic drugs (DMARDs) are available, there is still a medical need f…
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Journal:
Authors:
- Kjelgaard-Petersen CF,
- Platt A,
- Braddock M,
- Jenkins MA,
- Musa K,
- Graham E,
- Gantzel T,
- Slynn G,
- Weinblatt ME,
- Karsdal MA,
- Thudium CS,
- Bay-Jensen AC,
Rheumatology, Rheumatoid Arthritis
14. Feb 2018
Increased remodelling of interstitial collagens and basement membrane is suppressed by treatment in patients with rheumatoid arthritis: serological evaluation of a one-year prospective study of 149 Japanese patients
OBJECTIVES:
This prospective study aimed to use serological biomarkers for evaluation of, connective tissue turnover, in a population of 149 Japanese patients with rheumatoid arthritis (RA). It was aimed to investigate how the connective tissue was affected by treatment at follow-up after 1 year (+…
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Journal:
Authors:
- Gudmann NS,
- Hirata S,
- Karsdal MA,
- Kubo S,
- Bay-Jensen AC,
- Tanaka Y,
Rheumatology, Rheumatoid Arthritis
31. Jan 2018
IL-6 receptor inhibition modulates type III collagen and C-reactive protein degradation in rheumatoid arthritis patients with an inadequate response to anti-tumour necrosis factor therapy: analysis of connective tissue turnover in the tocilizumab RADIATE.
OBJECTIVES:
The objective of this study was to examine the tissue degradation in response to anti-IL6 receptor treatment in rheumatoid arthritis (RA) patients which are anti-TNF-α inadequate responders.
METHODS:
RADIATE was a randomised, double-blinded, placebo-controlled, parallel-group, phase…
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Journal:
Authors:
- Juhl P,
- Thudium CS,
- Gudmann NS,
- Karsdal MA,
- Bay-Jensen AC,
- Siebuhr AS,
Rheumatology, Rheumatoid Arthritis
23. Oct 2017
Blockade of GM-CSF pathway induced sustained suppression of myeloid and T cell activities in rheumatoid arthritis
OBJECTIVES:
Targeting the granulocyte-macrophage colony-stimulating factor (GM-CSF) pathway holds great potential in the treatment of inflammatory diseases. Mavrilimumab, a human monoclonal GM-CSF receptor-α antibody, has demonstrated clinical efficacy in RA. Our current study aimed to elucidate me…
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Journal:
Authors:
- Guo X,
- Higgs BW,
- Bay-Jensen AC,
- Wu Y,
- Karsdal MA,
- Kuziora M,
- Godwood A,
- Close D,
- Ryan PC,
- Roskos LK,
- White WI,
Rheumatology, Rheumatoid Arthritis
28. Aug 2017
Suppression of active, but not total MMP-3, is associated with treatment response in a phase III clinical study of rheumatoid arthritis
OBJECTIVE:
Biologics for rheumatoid arthritis (RA) patients with moderate to severe disease may preserve joint function. Matrix metalloproteinase 3 (MMP-3), a key tissue degrading protease, is highly elevated in RA. MMP-3, which measures the total pool of circulating MMP-3 species (cMMP3), is a com…
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Journal:
Authors:
- Siebuhr AS,
- Kjelgaard-Petersen CF,
- Sun S,
- Byrjalsen I,
- Christiansen C,
- Karsdal MA,
- Bay-Jensen AC,
Rheumatoid Arthritis, Rheumatology, Extracellular Matrix Research
17. Feb 2017
The minor collagens in articular cartilage
Articular cartilage is a connective tissue consisting of a specialized extracellular matrix (ECM) that dominates the bulk of its wet and dry weight. Type II collagen and aggrecan are the main ECM proteins in cartilage. However, little attention has been paid to less abundant molecular components, es…
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Journal:
Authors:
- Luo Y,
- Sinkeviciute D,
- He Y,
- Karsdal MA,
- Henrotin Y,
- Mobasheri A,
- Önnerfjord P,
- Bay-Jensen AC,
Rheumatology, Rheumatoid Arthritis
28. Mar 2016
Neo-Epitopes-Fragments of Cartilage and Connective Tissue Degradation in Early Rheumatoid Arthritis and Unclassified Arthritis
OBJECTIVE:
Tissue destruction in rheumatoid arthritis (RA) is predominantly mediated by matrix metalloproteinases (MMPs), thereby generating protein fragments. Previous studies have revealed that these fragments include MMP-mediated collagen type I, II, and III degradation, citrullinated and MMP-de…
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Journal:
Authors:
- Maijer KI,
- Gudmann NS,
- Karsdal MA,
- Gerlag DM,
- Tak PP,
- Bay-Jensen AC,
Rheumatology, Rheumatoid Arthritis
20. Jan 2016
Early changes in blood-based joint tissue destruction biomarkers are predictive of response to tocilizumab in the LITHE study
BACKGROUND:
Rheumatoid arthritis (RA) is characterized by gradual joint destruction. Tocilizumab (TCZ) significantly suppresses symptoms, however not all patients are protected from joint damage. We investigated whether early measurement of specific biomarkers could predict early joint protection r…
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Journal:
Authors:
- Bay-Jensen AC,
- Platt A,
- Siebuhr AS,
- Christiansen C,
- Byrjalsen I,
- Karsdal MA,
Rheumatology, Rheumatoid Arthritis
20. Sep 2014
Serological biomarkers of joint tissue turnover predict tocilizumab response at baseline
Rheumatoid arthritis (RA) is an autoimmune disease characterized by polyarticular joint inflammation resulting in massive tissue turnover. The turnover is partly mediated by an up-regulation of proteolytic enzymes, such as matrix metalloproteinases (MMPs).1 Matrix metalloproteinase 3 is 1 of the MMP…
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Journal:
Authors:
- Bay-Jensen AC,
- Byrjalsen I,
- Siebuhr AS,
- Christiansen C,
- Platt A,
- Karsdal MA,
Rheumatology, Rheumatoid Arthritis
5. Feb 2014
Effect of tocilizumab combined with methotrexate on circulating biomarkers of synovium, cartilage, and bone in the LITHE study
OBJECTIVE:
We investigated the effects of tocilizumab (TCZ) on joint tissue remodeling in patients with moderate to severely active RA by measuring tissue-specific biomarker.
METHODS:
The LITHE biomarker study (n = 740) was a phase III study of 4- and 8-mg/kg TCZ in combination with MTX. Early …
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Journal:
Authors:
- Bay-Jensen AC,
- Platt A,
- Byrjalsen I,
- Vergnoud P,
- Christiansen C,
- Karsdal MA,
Rheumatology, Rheumatoid Arthritis
27. Jan 2014
Rheumatoid arthritis - A case for Personalized Health Care?
Ethical, clinical, and economic considerations highlight the pressing need to advance the identification of optimal treatments for each individual patient. Personalized health care (PHC) may provide a significant benefit in the treatment of a number of clinical indications characterized by costly th…
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Journal:
Authors:
- Karsdal MA,
- Bay-Jensen AC,
- Henriksen K,
- Christiansen C,
- Genant HK,
- Chamberlain C,
- Platt A,
Rheumatology, Rheumatoid Arthritis
31. May 2013
Quantification of "end products" of tissue destruction in inflammation may reflect convergence of cytokine and signaling pathways - implications for modern clinical chemistry
The degree of inflammation in auto-immune diseases such as rheumatoid arthritis is often assessed in serum and used for diagnostic and prognostic purposes. The serum levels of acute inflammatory signaling molecules (C-reactive protein and serum amyloid A) in conjunction with the important pro-inflam…
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Authors:
Rheumatology, Rheumatoid Arthritis
4. Oct 2012
IL-6 receptor inhibition positively modulates bone balance in rheumatoid arthritis patients with an inadequate response to anti-tumor necrosis factor therapy: biochemical marker analysis of bone metabolism in the tocilizumab RADIATE study (NCT00106522)
OBJECTIVE:
To evaluate changes in biochemical markers of bone metabolism in response to tocilizumab in patients with anti-tumor necrosis factor-refractory rheumatoid arthritis (RA).
METHODS:
RADIATE was a randomized, double-blind, placebo-controlled, parallel-group phase 3 trial. C-reactive pro…
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Journal:
Authors:
- Karsdal MA,
- Schett G,
- Emery P,
- Harari O,
- Byrjalsen I,
- Kenwright A,
- Bay-Jensen AC,
- Platt A,
Rheumatology, Rheumatoid Arthritis
20. Sep 2012
Matrix metalloproteinase-dependent turnover of cartilage, synovial membrane, and connective tissue is elevated in rats with collagen induced arthritis
BACKGROUND:
Rheumatoid arthritis is a disease affecting the extracellular matrix of especially synovial joints. The thickness of the synovial membrane increases and surrounding tissue degrades, leading to altered collagen balance in the tissues. In this study, we investigated the altered tissue bal…
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Journal:
Authors:
- Siebuhr AS,
- Wang J,
- Karsdal MA,
- Bay-Jensen AC,
- Y J,
- Q Z,
Rheumatology, Osteoarthritis, Rheumatoid Arthritis
8. Dec 2011
Molecular serum and urine marker repertoire supporting clinical research on joint diseases
The need for improved analytical techniques in the study of slow, degenerative diseases such as rheumatoid arthritis and osteoarthritis has driven major efforts aimed at identifying biochemical markers of pathological processes in both diseases. A series of novel biochemical markers has surfaced and…
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Journal:
Authors:
- Qvist P,
- Bay-Jensen AC,
- Christiansen C,
- Sondergaard BC,
- Karsdal MA,