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.

Protein oxidation, nitration and glycation biomarkers for early-stage diagnosis of osteoarthritis of the knee and typing and progression of arthritic disease

“…Development of drugs to suppress oxidative damage and glycation damage to collagen in arthritis will be facilitated by availability of companion diagnostic tests based on related biomarkers [40]. There is no established method to detect eOA.…”

Mechanistically linked serum miRNAs distinguish between drug induced and fatty liver disease of different grades

“…Unfortunately, commonly used markers of liver injury lack specificity and do not distinguish between DIS and NAFLD of different grades but rely primarily on serum biochemistries, for instance by assaying serum alanine and aspartate aminotransferase activities as a means to examine the metabolic competence of the liver. In recent years molecular biomarkers of hepatotoxicity and their potential to improve understanding and management of DILI have been intensely researched as summarized in a recent research highlight 32 33 .…”

Right drug, right patient, right time: aspiration or future promise for biologics in rheumatoid arthritis?

“…Genome-wide association studies (GWAS) have identified a number of different loci associated with TNFi response in Caucasian and Asian populations, but other large independent studies have failed to confirm these associations [ 5 , 6 , 50 – 54 ]. Moreover, only two loci have reached genome-wide significance: PDE3A-SLCO1C1, containing genes encoding a phosphodiesterase A and a member of the anion transporter family, for which the C > T polymorphism was associated with reduced efficacy to adalimumab, etanercept and infliximab with high significance ( p = 10 –11 ) [ 53 , 55 ]; and CD84, encoding SLAM family member 5, in which the G > A single nucleotide polymorphism (SNP) predicted responsiveness to etanercept ( p = 10 –8 ) [ 56 ].…”

“…Furthermore, the varied response pattern reflects the increasingly recognised concept of RA as a syndrome —that is, heterogeneous aetiology and pathophysiology with many immunological variants and a common clinical phenotype [ 4 ]. The cumulative evidence base highlights the existence of several pathobiological signatures that may associate with individual immunopathogenic patient profiles, and thus a rational specific therapeutic agent [ 5 – 8 ]. Thus, it is somewhat expected that the same treatment strategy will not achieve similar results in every RA patient.…”