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The fibroid phenotype of biological naïve patients with rheumatoid arthritis are less likely to respond to anti-IL-6R treatment.

May 10, 2024

Sci Rep

Abstract Type III collagen gene expression is upregulated in the synovium of patients with rheumatoid arthritis (RA) presenting the fibroid phenotype. The soluble type III collagen formation biomarker, PRO-C3, is known to measure fibrogenesis in fibrotic diseases. In this exploratory study, we aimed to investigate the association between fibrogenesis (PRO-C3) and the disease- and treatment […]

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Changes in type VI collagen degradation reflect clinical response to treatment in rheumatoid arthritis patients treated with tocilizumab.

January 2, 2024

Arthritis Res Ther

Abstract OBJECTIVES Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammation in multiple articular joints, causing pain, joint damage, and loss of joint function. Despite the successful development of disease-modifying therapies, the heterogeneity of RA means that a significant proportion of patients respond poorly to treatment. This highlights the need for personalized medicine […]

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Baseline serum levels of cross-linked carboxy-terminal telopeptide of type I collagen predict abatacept treatment response in methotrexate-naive, anticitrullinated protein antibody-positive patients with early rheumatoid arthritis.

December 1, 2022

RMD Open

Abstract OBJECTIVE To investigate correlations between biomarkers of bone remodelling and extracellular matrix turnover with baseline disease activity and treatment response in patients with early rheumatoid arthritis (RA). METHODS ssessing ery arly heumatoid arthritis reatment-2 (AVERT-2; NCT02504268) included disease-modifying antirheumatic drug-naive, anti-citrullinated protein antibody (ACPA)-positive patients randomised to weekly subcutaneous abatacept+methotrexate (MTX) or abatacept placebo+MTX […]

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Connective tissue remodelling is differently modulated by tocilizumab versus methotrexate monotherapy in patients with early rheumatoid arthritis: the AMBITION study.

January 7, 2021

Arthritis Res Ther

Abstract OBJECTIVE Associations between rheumatoid arthritis (RA) and effect of treatment at the tissue levels are poorly understood. We investigated the scope of released extracellular matrix (ECM) metabolites as a consequence of tissue remodelling in patients treated with methotrexate (MTX) and tocilizumab (TCZ) compared to placebo. METHODS Tissue metabolites from 387 RA patients treated with […]

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The Janus kinase 1/2 inhibitor baricitinib reduces biomarkers of joint destruction in moderate to severe rheumatoid arthritis.

October 12, 2020

Arthritis Res Ther

Abstract BACKGROUND Tissue released blood-based biomarkers can provide insight into drug mode of action and response. To understand the changes in extracellular matrix turnover, we analyzed biomarkers associated with joint tissue turnover from a phase 3, randomized, placebo-controlled study of baricitinib in patients with active rheumatoid arthritis (RA). METHODS Serum biomarkers associated with synovial inflammation […]

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Identification of heterogenous treatment response trajectories to anti-IL6 receptor treatment in rheumatoid arthritis.

August 18, 2020

Sci Rep

Abstract Rheumatoid arthritis (RA) is a chronic inflammatory disease with fluctuating course of progression. Despite substantial improvement in treatments in recent years, treatment response is still not guaranteed. The aim of this study was to identify variation in Disease Activity Score 28 (DAS28) of RA patients in response to Tocilizumab, and to investigate both molecular […]

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Osteoarthritis phenotypes and novel therapeutic targets.

July 1, 2019

Biochem Pharmacol

Abstract The success of disease-modifying osteoarthritis drug (DMOAD) development is still elusive. While there have been successes in preclinical and early clinical studies, phase 3 clinical trials have failed so far and there is still no approved, widely available DMOAD on the market. The latest research suggests that, among other causes, poor trial outcomes might […]

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Incidence of total hip and total knee replacements from the prospective epidemiologic risk factor study: considerations for event driven clinical trial design.

June 26, 2019

BMC Musculoskelet Disord

Abstract BACKGROUND Osteoarthritis (OA) leads to joint failure and total joint replacement (TJR, either hip (H) or knee (K)). Worsening of pain and joint space narrowing are believed to be surrogates for joint failure; however, we hypothesize that TJR, as a reflection of joint failure, can be used as an endpoint in event-driven clinical trials […]

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Type IV collagen metabolism is associated with disease activity, radiographic progression and response to tocilizumab in rheumatoid arthritis.

October 1, 2018

Clin Exp Rheumatol

Abstract 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 matrix of the synovial lining layer. We aimed to investigate the association […]

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Translational Biomarkers and Ex Vivo Models of Joint Tissues as a Tool for Drug Development in Rheumatoid Arthritis.

September 1, 2018

Arthritis Rheumatol

Abstract OBJECTIVE Rheumatoid arthritis (RA) is a chronic and degenerative autoimmune joint disease that leads to disability, reduced quality of life, and increased mortality. Although several synthetic and biologic disease-modifying antirheumatic drugs are available, there is still a medical need for novel drugs that control disease progression. As only 10% of experimental drug candidates for […]

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