Immunohistological assessment of the synovial tissue in small joints in rheumatoid arthritis: validation of a minimally invasive ultrasound-guided synovial biopsy procedure

Ultrasound-guided synovial biopsy is a safe, well-tolerated, and effective method to collect good-quality synovial tissue from all types of joints for clinical and research purposes. Although synovial biopsy cannot be used to distinguish between types of inflammatory rheumatic disease, analysis of synovial tissue has led to remarkable advances in the understanding of the pathobiology of rheumatoid arthritis and other inflammatory rheumatic diseases. Synovitis is the hallmark of these diseases; hence, accessing the core of the pathological process, synovial tissue, provides an opportunity to gather information with potential diagnostic and prognostic utility.

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Evaluating antirheumatic treatments using synovial biopsy: a recommendation for standardisation to be used in clinical trials

Annals of the Rheumatic Diseases ◽

10.1136/ard.2010.139550 ◽

2010 ◽

Vol 70 (3) ◽

pp. 423-427 ◽

Cited By ~ 75

Author(s):

Marleen G H van de Sande ◽

Danielle M Gerlag ◽

Beatrijs M Lodde ◽

Lisa G M van Baarsen ◽

Stefano Alivernini ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Clinical Trials ◽

Translational Research ◽

Synovial Tissue ◽

Therapeutic Targets ◽

Synovial Biopsy ◽

Prognostic Biomarkers

Inflammation of synovium is one of the hallmarks of rheumatoid arthritis (RA). Analysis of synovial tissue has increased our understanding of RA pathogenesis, aided in identifying potential therapeutic targets and has been used in the response and mechanistic evaluation of antirheumatic treatments. In addition, studies are ongoing, aimed at the identification of diagnostic and prognostic biomarkers in the synovium. This paper outlines the currently used procedures for sampling and processing of synovial tissue, and presents a standardised recommendation to support multicentre translational research.

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Transcriptional Profiling of Synovial Macrophages Using Minimally Invasive Ultrasound-Guided Synovial Biopsies in Rheumatoid Arthritis

Arthritis & Rheumatology ◽

10.1002/art.40453 ◽

2018 ◽

Vol 70 (6) ◽

pp. 841-854 ◽

Cited By ~ 19

Author(s):

Arthur M. Mandelin ◽

Philip J. Homan ◽

Alexander M. Shaffer ◽

Carla M. Cuda ◽

Salina T. Dominguez ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Minimally Invasive ◽

Transcriptional Profiling ◽

Ultrasound Guided

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Patient-reported outcomes and safety in patients undergoing synovial biopsy: comparison of ultrasound-guided needle biopsy, ultrasound-guided portal and forceps and arthroscopic-guided synovial biopsy techniques in five centres across Europe

RMD Open ◽

10.1136/rmdopen-2018-000799 ◽

2018 ◽

Vol 4 (2) ◽

pp. e000799 ◽

Cited By ~ 9

Author(s):

Søren Andreas Just ◽

Frances Humby ◽

Hanne Lindegaard ◽

Laurent Meric de Bellefon ◽

Patrick Durez ◽

...

Keyword(s):

Adverse Events ◽

Corticosteroid Therapy ◽

Needle Biopsy ◽

Patient Reported Outcomes ◽

Safety Data ◽

Synovial Biopsy ◽

Ultrasound Guided ◽

Biopsy Procedure ◽

Patient Reported ◽

Biopsy Methods

BackgroundWe present a European multicenter study, comparing safety data and patient-reported outcomes (PRO) from patients undergoing synovial biopsy using ultrasound-guided needle biopsy (US-NB), ultrasound-guided portal and forceps (US-P&F) or arthroscopic-guided (AG) procedures.ObjectivesTo describe safety and PRO data on joint indices of pain, stiffness and swelling before and after biopsy, procedural discomfort, joint status compared with before biopsy and willingness to undergo a second biopsy for each technique and compare the three techniques. To evaluate the impact on PRO and safety data of corticosteroid therapy as part of the biopsy procedure and sequential biopsy procedures.MethodsData were collected on the day of biopsy and 7–14 days postprocedure. Joint pain, swelling and stiffness indices were recorded as 0–100 mm Visual Analogue Scale; qualitative outcome variables on five-point Likert scales. Groups were compared with linear regression, adjusting for disease activity, corticosteroid therapy and prebiopsy PRO value and accounting for repeated measurements.ResultsA total of 524 synovial biopsy procedures were documented (402 US-NB, 65 US-P&F and 57 AGSB). There were eight adverse events (1.5%) with no difference between biopsy methods (p=0.55). All PROs were improved 2 weeks postprocedure, and there were no differences in postbiopsy change in PROs between biopsy methods. Corticosteroid administration, whether intramuscular (n=62) or intra-articular (n=38), did not result in more adverse events (p=0.81) and was associated with reduction in postbiopsy swelling (p<0.01). Sequential biopsy procedures (n=103 patients) did not result in more adverse events (p=0.61) or worsening in PRO data.ConclusionOverall, our results do not suggest a significant difference in safety or patient tolerability between US-NB, US-P&F and AGSB sampling. Further, corticosteroid therapy as part of the biopsy procedure and sequential biopsies is safe and well tolerated in patients.

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BIOlogical Factors that Limit sustAined Remission in rhEumatoid arthritis (the BIO-FLARE study): protocol for a non-randomised longitudinal cohort study

BMC Rheumatology ◽

10.1186/s41927-021-00194-3 ◽

2021 ◽

Vol 5 (1) ◽

Author(s):

Fiona Rayner ◽

Amy E. Anderson ◽

Kenneth F. Baker ◽

Christopher D. Buckley ◽

Bernard Dyke ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Cohort Study ◽

Immune Cell ◽

Previous Treatment ◽

Synovial Biopsy ◽

Longitudinal Cohort Study ◽

Sustained Remission ◽

Ultrasound Guided ◽

Multivariate Statistical ◽

Longitudinal Cohort

Abstract Background Our knowledge of immune-mediated inflammatory disease (IMID) aetiology and pathogenesis has improved greatly over recent years, however, very little is known of the factors that trigger disease relapses (flares), converting diseases from inactive to active states. Focussing on rheumatoid arthritis (RA), the challenge that we will address is why IMIDs remit and relapse. Extrapolating from pathogenetic factors involved in disease initiation, new episodes of inflammation could be triggered by recurrent systemic immune dysregulation or locally by factors within the joint, either of which could be endorsed by overarching epigenetic factors or changes in systemic or localised metabolism. Methods The BIO-FLARE study is a non-randomised longitudinal cohort study that aims to enrol 150 patients with RA in remission on a stable dose of non-biologic disease-modifying anti-rheumatic drugs (DMARDs), who consent to discontinue treatment. Participants stop their DMARDs at time 0 and are offered an optional ultrasound-guided synovial biopsy. They are studied intensively, with blood sampling and clinical evaluation at weeks 0, 2, 5, 8, 12 and 24. It is anticipated that 50% of participants will have a disease flare, whilst 50% remain in drug-free remission for the study duration (24 weeks). Flaring participants undergo an ultrasound-guided synovial biopsy before reinstatement of previous treatment. Blood samples will be used to investigate immune cell subsets, their activation status and their cytokine profile, autoantibody profiles and epigenetic profiles. Synovial biopsies will be examined to profile cell lineages and subtypes present at flare. Blood, urine and synovium will be examined to determine metabolic profiles. Taking into account all generated data, multivariate statistical techniques will be employed to develop a model to predict impending flare in RA, highlighting therapeutic pathways and informative biomarkers. Despite initial recruitment to time and target, the SARS-CoV-2 pandemic has impacted significantly, and a decision was taken to close recruitment at 118 participants with complete data. Discussion This study aims to investigate the pathogenesis of flare in rheumatoid arthritis, which is a significant knowledge gap in our understanding, addressing a major unmet patient need. Trial registration The study was retrospectively registered on 27/06/2019 in the ISRCTN registry 16371380.

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Success Rate and Utility of Ultrasound-guided Synovial Biopsies in Clinical Practice

The Journal of Rheumatology ◽

10.3899/jrheum.151441 ◽

2016 ◽

Vol 43 (12) ◽

pp. 2113-2119 ◽

Cited By ~ 15

Author(s):

Aurélie Najm ◽

Carl Orr ◽

Marie-Françoise Heymann ◽

Géraldine Bart ◽

Douglas J. Veale ◽

...

Keyword(s):

Clinical Practice ◽

Success Rate ◽

Synovial Tissue ◽

Synovial Biopsy ◽

Ultrasound Guided ◽

Undifferentiated Arthritis ◽

Biopsy Needle ◽

Us Guidance ◽

Rate Of Success

Objective.The utility of synovial biopsy in increasing our understanding of the pathogenesis of inflammatory arthropathies, as well as in evaluating treatments, is well established. Ultrasound (US) allows synovial assessment and therefore assists in biopsying synovial tissue in a safe and well-tolerated manner. This study’s objectives were to (1) determine the rate of success in retrieving synovial tissue using US guidance, (2) describe the indications for US-guided synovial biopsies in the clinical setting, (3) determine how frequently the synovial biopsy can lead to a clear diagnosis, and (4) assess the quality of the synovial tissue obtained using this technique.Methods.Synovial biopsies of small and large joints were performed under US guidance between February 2007 and December 2014 using a semiautomatic core biopsy needle. The biopsy procedure was considered successful if synovial tissue was found at histological examination.Results.Seventy-four patients with undifferentiated arthritis underwent 76 synovial biopsies. The success rate in retrieving synovial tissue was 81.6% (62/76). One patient taking acetyl salicylic acid at 75 mg at the time of the biopsy presented with hemarthrosis 48 h after the procedure, which resolved following simple arthrocentesis. A definitive diagnosis was achieved in 16% of the patients where synovial tissue was sampled successfully.Conclusion.US-guided synovial biopsies in clinical practice can be performed safely on patients with undifferentiated arthritis and with heterogeneous presentations. The rate of success in acquiring synovial tissue is high. The procedure usually retrieves quality tissue and leads to a definite diagnosis in a significant minority of patients.

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Evaluation of Minimally Invasive, Ultrasound-guided Synovial Biopsy Techniques by the OMERACT Filter — Determining Validation Requirements

The Journal of Rheumatology ◽

10.3899/jrheum.141199 ◽

2015 ◽

Vol 43 (1) ◽

pp. 208-213 ◽

Cited By ~ 21

Author(s):

Frances Humby ◽

Stephen Kelly ◽

Serena Bugatti ◽

Antonio Manzo ◽

Andrew Filer ◽

...

Keyword(s):

Clinical Trials ◽

Clinical Practice ◽

Minimally Invasive ◽

Synovial Tissue ◽

Working Group ◽

Current Data ◽

Synovial Biopsy ◽

Limited Data ◽

Global Consensus ◽

Robust Techniques

Objective.Because limited data currently support the clinical utility of peripherally expressed biomarkers in guiding treatment decisions for patients with rheumatoid arthritis, the search has turned to the disease tissue. The strategic aim of the Outcome Measures in Rheumatology (OMERACT) synovitis working group over the years has been to develop novel diagnostic and prognostic synovial biomarkers. A critical step in this process is to refine and validate minimally invasive, technically simple, robust techniques to sample synovial tissue, for use both in clinical trials and routine clinical practice. The objective of the synovitis working group (SWG) at OMERACT 12 (2014) was to examine whether recently developed ultrasound (US)-guided synovial biopsy techniques could be validated according to the OMERACT filter for future clinical use recommendation.MethodsThe SWG examined whether current data reporting US-guided synovial biopsy of both large and small joints addressed the OMERACT filters of truth, discrimination, and feasibility.Results.There are currently limited data examining the performance of US-guided synovial biopsy, mainly from observational studies. Thus, it remains critical to evaluate its performance, within the clinical trials context, against the current gold standard of arthroscopic biopsy, with particular reference to: (1) synovial tissue yield, (2) capacity to determine treatment response as measured by a validated synovial biomarker, and (3) tolerability of the procedure.Conclusion.We summarize the discrete work packages agreed to as requirements to validate US-guided synovial biopsy and therefore lead to a global consensus on the use of synovial biopsy for research and clinical practice.

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