Synovial Tissue Analysis for the Discovery of Diagnostic and Prognostic Biomarkers in Patients with Early Arthritis: Table 1.

Hair, Maria J. H. de; Harty, Len; Gerlag, Daniëlle M.; Pitzalis, Costantino; Veale, Douglas J.; Tak, Paul P.

doi:10.3899/jrheum.110426

Cited by 35 publications

(28 citation statements)

References 41 publications

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“…Having a cohort of early arthritis patients with clinical data, histological data, DNA and mRNA arrays plus proteomics is an instrumental resource for investigating differences in synovial tissue, comparing several inflammatory joint diseases with persistent self-limiting, persistent active disease as well as erosive and non-erosive disease. 74 Most research with synovial biopsies has been performed from RA patients but some results suggest that synovial tissue sampling may be used in other inflammatory arthropathies such as psoriatic arthritis. 71,[75][76][77] This research aims to gain a fuller understanding of disease pathogenesis, mechanisms of action of current treatments, and the identification of novel targets and biomarkers.…”

Section: Retrieving Synovial Tissue Samplesmentioning

confidence: 99%

Synovial tissue research: a state-of-the-art review

et al. 2017

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The synovium is the major target tissue of inflammatory arthritides such as rheumatoid arthritis (RA). The study of synovial tissue has advanced significantly over a number of decades from arthroplasty, blind needle biopsy and more recently facilitated by arthroscopic and ultrasonographic technology that allows easier visualisation and improves the reliability of obtaining synovial biopsies. The potential for study of pathogenesis, patient stratification, discovery of biomarkers and novel targets, as well as validation of therapy, have all been progressed rapidly in the last decade, facilitated by increasingly diverse and sophisticated analytical and technological approaches. In this review we describe clinical and translational developments in the field of synovial tissue research, outlining current and novel investigative technologies, and highlight their application to advance our understanding of the aforegoing imperatives.3

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Section: Retrieving Synovial Tissue Samplesmentioning

confidence: 99%

Synovial tissue research: a state-of-the-art review

et al. 2017

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“…Numbers of CD68+ macrophages within rheumatoid synovial sublining tissue have demonstrated a positive correlation with clinical symptoms 20 , and macrophages are a source of key mediators [e.g., TNF, interleukin (IL) 6, IL-23]. Collectively, this led to the hypothesis that targeting macrophages may result in successful new therapeutics.…”

Section: Discussionmentioning

confidence: 99%

Results from a Phase IIA Parallel Group Study of JNJ-40346527, an Oral CSF-1R Inhibitor, in Patients with Active Rheumatoid Arthritis despite Disease-modifying Antirheumatic Drug Therapy

et al. 2015

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Objective.To assess the efficacy and safety of JNJ-40346527, a selective inhibitor of colony-stimulating factor-1 (CSF-1) receptor kinase that acts to inhibit macrophage survival, proliferation, and differentiation in patients with active rheumatoid arthritis (RA) despite disease-modifying antirheumatic drug (DMARD) therapy.Methods.In this randomized, double-blind, placebo-controlled, parallel group study, adults were randomized (2:1) to receive oral JNJ-40346527 100 mg or placebo twice daily through Week 12. Patients with RA had disease activity [≥ 6 swollen/≥ 6 tender joints, C-reactive protein (CRP) ≥ 0.8 mg/dl] despite DMARD therapy for ≥ 6 months. The primary endpoint was change from baseline at Week 12 in the 28-joint Disease Activity Score with CRP (DAS28-CRP). Pharmacokinetic/pharmacodynamic analyses were also performed, and safety was assessed through Week 16.Results.Ninety-five patients were treated (63 JNJ-40346527, 32 placebo); 8 patients discontinued treatment (6 JNJ-40346527, 2 placebo) through Week 12. Mean improvements in DAS28-CRP from baseline to Week 12 were 1.15 for the JNJ-40346527 group and 1.42 for the placebo group (p = 0.30); thus, a statistically significant difference was not observed for the primary endpoint. Pharmacokinetic exposure to JNJ-40346527 and its active metabolites was above the projected concentration needed for pharmacologic activity, and effective target engagement and proof of activity were demonstrated by increased levels of CSF-1 and decreased CD16+ monocytes in JNJ-40346527–treated, but not placebo-treated, patients. Thirty-seven (58.7%) JNJ-40346527–treated and 16 (50.0%) placebo-treated patients reported ≥ 1 adverse event (AE); 1 (1.6%) JNJ-40346527–treated and 3 (9.4%) placebo-treated patients reported ≥ 1 serious AE.Conclusion.Although adequate exposure and effective peripheral target engagement were evident, JNJ-40346527 efficacy was not observed in patients with DMARD-refractory active RA. ClinicalTrials.gov identifier: NCT01597739. EudraCT Number: 2011-004529-28.

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“…Forty-one patients from our early arthritis cohort with less than 12 months disease duration and active knee (n=28) or ankle (n=13) arthritis were included 26. None of the patients had received disease modifying antirheumatic drugs, corticosteroids or biological treatment before inclusion.…”

Section: Methodsmentioning

confidence: 99%