The treatment of rheumatoid arthritis (RA) has been transformed with the 
introduction of biologic disease modifying anti-rheumatic drugs (bDMARD) and 
more recently, targeted synthetic DMARD (tsDMARD) therapies in the form of 
janus-kinase inhibitors. Nevertheless, response to these agents varies such that 
a trial and error approach is adopted; leading to poor patient quality of life, 
and long-term outcomes. There is thus an urgent need to identify effective 
biomarkers to guide treatment selection. A wealth of research has been invested 
in this field but with minimal progress. Increasingly recognized is the 
importance of evaluating synovial tissue, the primary site of RA, as opposed to 
peripheral blood-based investigation. In this mini-review, we summarize the 
literature supporting synovial tissue heterogeneity, the conceptual basis for 
stratified therapy. This includes recognition of distinct synovial 
pathobiological subtypes and associated molecular pathways. We also review 
synovial tissue studies that have been conducted to evaluate the effect of 
individual bDMARD and tsDMARD on the cellular and molecular characteristics, 
with a view to identifying tissue predictors of response. Initial observations 
are being brought into the clinical trial landscape with stratified biopsy 
trials to validate toward implementation. Furthermore, development of tissue 
based omics technology holds still more promise in advancing our understanding 
of disease processes and guiding future drug selection.