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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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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 study.

August 1, 2018

Clin Exp Rheumatol

Abstract 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 III trial. RA patients with previous inadequate response to anti-TNFα therapy (n=299) were randomly assigned to tocilizumab […]

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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.

June 1, 2018

Clin Exp Rheumatol

Abstract 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 (+/- 6 weeks) with either methotrexate (n=23) alone, or in […]

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Suppression of active, but not total MMP-3, is associated with treatment response in a phase III clinical study of rheumatoid arthritis.

February 1, 2018

Clin Exp Rheumatol

Abstract 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 commonly measured biomarker in rheumatology. The aim was to investigate the […]

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Blockade of GM-CSF pathway induced sustained suppression of myeloid and T cell activities in rheumatoid arthritis.

January 1, 2018

Rheumatology (Oxford)

Abstract 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 mechanisms of action and identify peripheral biomarkers associated with therapeutic responses of GM-CSF antagonism in RA. METHODS A […]

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Identification of serological biomarker profiles associated with total joint replacement in osteoarthritis patients.

June 1, 2017

Osteoarthritis Cartilage

Abstract OBJECTIVE Establish a biomarker panel associated with all-cause total joint replacement (TJR) through identification of patients with osteoarthritis (OA) who do or do not progress to TJR and investigate effects of nonsteroidal anti-inflammatory drugs (NSAIDs). DESIGN Serum samples from patients enrolled in phase III trials of tanezumab who experienced TJR (n = 174) or matched patients […]

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Early changes in blood-based joint tissue destruction biomarkers are predictive of response to tocilizumab in the LITHE study.

January 20, 2016

Arthritis Res Ther

Abstract 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 response to tocilizumab. METHOD Serum biomarkers (CRPM, VICM, C1M, C2M, C3M (MMP-degraded CRP, vimentin type I, II […]

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Suppression of T Cell Activation and Collagen Accumulation by an Anti-IFNAR1 mAb, Anifrolumab, in Adult Patients with Systemic Sclerosis.

October 1, 2015

J Invest Dermatol

Abstract Type I IFNs are implicated in the pathophysiology of systemic sclerosis (SSc). Recently, a Phase I open-label trial was conducted with an anti-IFNAR1 receptor antibody (anifrolumab) in adult SSc patients. In this study, we aim to assess the downstream effects of anifrolumab and elucidate the role of type I IFN in SSc. Serum proteins […]

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Effect of tocilizumab combined with methotrexate on circulating biomarkers of synovium, cartilage, and bone in the LITHE study.

February 1, 2014

Semin Arthritis Rheum

Abstract 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 response was evaluated at week 16 as […]

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