The relationship between clinical disease activity, synovial inflammatory profile, and treatment response in rheumatoid arthritis

Synovial tissue is widely considered to be a strong candidate for contributing to the development of individualised therapeutic strategies for the treatment and management of rheumatoid arthritis. Recently, several factors have enabled major developments in synovial tissue analysis: (1) improvement in synovial tissue biopsy techniques; (2) availability of powerful biotechnologies with increasing granularity; (3) recruitment of larger cohorts of patients; (4) development of recommendations to standardise synovial tissue analysis; and (5) an expanded therapeutic armamentarium of targeted therapies. Although recent studies have suggested the existence of rheumatoid arthritis subtypes based on the synovial tissue inflammatory profile, with potential therapeutic implications, other studies have yielded different results. In this Viewpoint we discuss and contextualise the findings of recent major studies in the field of synovial tissue. We highlight how disease activity, synovial tissue inflammatory burden, and response to therapy are interdependent features in rheumatoid arthritis, both earlier and later in the disease course. From there, we discuss how this multidirectional relationship has impacted (and potentially influenced the interpretation of) the findings of synovial tissue-based studies. Finally, we discuss the different hypotheses explaining the link between synovial tissue, clinical features, and therapeutic response.