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Is there a role of synovial biopsy in drug development?

Filkova M, Cope A, Mant T, Galloway J - BMC Musculoskelet Disord (2016)

Bottom Line: The pathological hallmark of RA is inflammation of the synovium characterized by involvement of inflammatory and resident stromal cells, soluble mediators and signalling pathways leading to irreversible joint destruction.Modern techniques have made the procedure much more accessible and ultrasound guided biopsies represent a safe and acceptable option.However, there are still caveats with regard to both the choice of technique and analytical methods.

View Article: PubMed Central - PubMed

Affiliation: Academic Department of Rheumatology, Weston Education Centre, King's College London, Cutcombe Road, SE5 9RJ, London, UK.

ABSTRACT
Rheumatoid arthritis (RA) is an autoimmune disease which causes significant pain, joint deformity, functional disability. The pathological hallmark of RA is inflammation of the synovium characterized by involvement of inflammatory and resident stromal cells, soluble mediators and signalling pathways leading to irreversible joint destruction. The treatment goal in RA has evolved over the last decade towards a target of disease remission that is achieved in less than a third of patients in clinical trials. The lack of therapeutic response to current treatments is suggestive of alternative drivers of RA pathogenesis that might serve as promising therapeutic targets. There are data to justify the use of synovial tissue in early drug development. Synovial tissue represents an appropriate compartment to be studied in patients with inflammatory arthritis and provides information that is distinct from peripheral blood. Modern techniques have made the procedure much more accessible and ultrasound guided biopsies represent a safe and acceptable option. Advances in analytic technologies allowing transcriptomic level of analysis can provide unique inside to target organ/tissue following the exposure to investigational medicinal product. However, there are still caveats with regard to both the choice of technique and analytical methods. Therefore the significance of synovial biopsy remains to be determined in future clinical trials. The aim of the current debate is to explore the potential for accessing and evaluating synovial tissue in early drug development, to summarize lessons we have learned from clinical trials and to discuss the challenges that have arisen so far.

No MeSH data available.


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Methods of synovial tissue analysis with implications for drug development
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Fig2: Methods of synovial tissue analysis with implications for drug development

Mentions: As summarized above, the optimal approach to obtain representative samples is to directly visualize inflamed tissue arthroscopically or with ultrasound. Direct visualization during biopsy minimizes sampling error, enables acquisition of biopsies from precise locations within joints and provides reproducible good quality tissues. Available techniques for synovial tissue analysis will now be summarized (Fig. 2).Fig. 2


Is there a role of synovial biopsy in drug development?

Filkova M, Cope A, Mant T, Galloway J - BMC Musculoskelet Disord (2016)

Methods of synovial tissue analysis with implications for drug development
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4837502&req=5

Fig2: Methods of synovial tissue analysis with implications for drug development
Mentions: As summarized above, the optimal approach to obtain representative samples is to directly visualize inflamed tissue arthroscopically or with ultrasound. Direct visualization during biopsy minimizes sampling error, enables acquisition of biopsies from precise locations within joints and provides reproducible good quality tissues. Available techniques for synovial tissue analysis will now be summarized (Fig. 2).Fig. 2

Bottom Line: The pathological hallmark of RA is inflammation of the synovium characterized by involvement of inflammatory and resident stromal cells, soluble mediators and signalling pathways leading to irreversible joint destruction.Modern techniques have made the procedure much more accessible and ultrasound guided biopsies represent a safe and acceptable option.However, there are still caveats with regard to both the choice of technique and analytical methods.

View Article: PubMed Central - PubMed

Affiliation: Academic Department of Rheumatology, Weston Education Centre, King's College London, Cutcombe Road, SE5 9RJ, London, UK.

ABSTRACT
Rheumatoid arthritis (RA) is an autoimmune disease which causes significant pain, joint deformity, functional disability. The pathological hallmark of RA is inflammation of the synovium characterized by involvement of inflammatory and resident stromal cells, soluble mediators and signalling pathways leading to irreversible joint destruction. The treatment goal in RA has evolved over the last decade towards a target of disease remission that is achieved in less than a third of patients in clinical trials. The lack of therapeutic response to current treatments is suggestive of alternative drivers of RA pathogenesis that might serve as promising therapeutic targets. There are data to justify the use of synovial tissue in early drug development. Synovial tissue represents an appropriate compartment to be studied in patients with inflammatory arthritis and provides information that is distinct from peripheral blood. Modern techniques have made the procedure much more accessible and ultrasound guided biopsies represent a safe and acceptable option. Advances in analytic technologies allowing transcriptomic level of analysis can provide unique inside to target organ/tissue following the exposure to investigational medicinal product. However, there are still caveats with regard to both the choice of technique and analytical methods. Therefore the significance of synovial biopsy remains to be determined in future clinical trials. The aim of the current debate is to explore the potential for accessing and evaluating synovial tissue in early drug development, to summarize lessons we have learned from clinical trials and to discuss the challenges that have arisen so far.

No MeSH data available.


Related in: MedlinePlus