Synovial biopsies for molecular definition of rheumatoid arthritis and treatment response phenotyping: where can we improve?

IntroductionThe extensive knowledge gained in the cellular and molecular mechanisms underlying Rheumatoid Arthritis (RA) pathogenesis has led to therapeutic advances. However, up to 10-20% of patients fail to respond to multiple therapeutic agents being classified as multi-drugresistant. A key challenge moving forward will be the implementation of synovial biopsies in clinical practice to facilitate the shift from the current trial-and-error strategy toward new forms of clinical trials. Biomarker-driven trials have the potential to improve drug selection and patient stratification, reduce economic costs and unnecessary drug-related toxicity.Areas coveredThis special report explores the clinical and research applications of synovial biopsy, the advancement in the molecular pathobiology of RA to better understand disease pathogenesis and treatment response, and the way forward for the paradigm shift needed.Expert opinionIn the current era of highly targeted biologic drugs which have dramatically transformed the outlook of RA patients, the use of synovial biopsy represents a valuable practical tool to dissect disease pathogenesis and, consequently, treatment response. In the near future, it is hoped that technological advances will allow for speeding up synovial molecular analysis and that the design of new biomarker-driven trials will enable the allocation of patients to more effective treatment.