Current and future trends in biomarker discovery and development of companion diagnostics for arthritis

Abstract

Musculoskeletal diseases such as rheumatoid arthritis are complex multifactorial disorders that are chronic in nature and debilitating for patients. A number of drug families are available to clinicians to manage these disorders but few tests exist to target these to the most responsive patients. As a consequence, drug failure and switching to drugs with alternate modes of action is common. In parallel, a limited number of laboratory tests are available which measure biological indicators or ‘biomarkers’ of disease activity, autoimmune status, or joint damage. There is a growing awareness that assimilating the fields of drug selection and diagnostic tests into ‘companion diagnostics’ could greatly advance disease management and improve outcomes for patients. This review aims to highlight: the current applications of biomarkers in rheumatology with particular focus on companion diagnostics; developments in the fields of proteomics, genomics, microbiomics, imaging and bioinformatics and how integration of these technologies into clinical practice could support therapeutic decisions.

Keywords:

• bioinformatics.companion diagnostics
• genomics
• imaging
• microbiomics
• proteomics
• rheumatology
• stratified medicine

Financial & competing interests disclosure

A patent (WO2009/074326) for ‘the use of KIR genes for predicting response to anti-TNF-α therapy’ was deposited by the University of Ulster (CM McGeough, AJ Bjourson). DSG would like to acknowledge support for his position from ILEX Trust. TB would like to acknowledge funding for The Northern Ireland Centre for Stratified Medicine by Invest Northern Ireland (part funded by the European Regional Development Fund), the University of Ulster, The Department of Health and ILEX Regeneration Trust. TB is also grateful for support from the Technology Strategy Board for the RHEUMASTRAT project. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Though many ‘biomarkers’ are discovered, few are robustly validated through to clinical utility.

• There is a growing need for companion diagnostics to guide the use of high-cost biologic drugs prescribed for a range of musculoskeletal disorders.

• Protein tests can reveal real-time measures of disease activity, joint damage, autoimmunity and drug pharmacodynamics.

• Genetic tests of variation in DNA sequence can help stratify patients by risk of drug failure or aggressive disease.

• Epigenetic analyses of specific cells and tissues could present a means to further stratify and treat musculoskeletal disorders.

• With further research, the gut microbiome could present a means to further stratify and treat musculoskeletal disorders.

• Robust bioinformatics analyses are important to integrate datasets from laboratory tests and clinical assessments and to confidently validate multiplex biomarkers.

• Management of arthritis by companion diagnostics offers benefits to the patient, the clinician and health authorities.