Rheumatoid Arthritis: Biomarkers and Comorbidities

The last 30 years have seen tremendous advances in the management of rheumatoid arthritis (RA), with increased knowledge on disease pathogenesis, earlier diagnosis, better use of conventional synthetic (cs) disease-modifying antirheumatic drugs (DMARDs), and development of an increasing number of biologic (b) and targeted synthetic (ts) DMARDs with different modes of action. As a result, the prognosis of RA has changed, and many patients are now capable of achieving adequate disease control, paralleled by improved function, better quality of life, and increased life expectancy [1, 2]. In this overall encouraging scenario, however, there are some grey areas that still limit the achievement of optimal outcomes in all patients. Disease presentation, aggressiveness, and response to therapy might be extremely variable among individuals, ranging from very mild to rapidly progressive and multiresistant forms. Despite such recognized diversity, the absence of robust prognostic tools limits the possibility of personalized strategies, and the management of RA remains based on a “trial-and-error’ and “one-size-fits-all” approach. Clinical and biological research is intensively working on the identification of possible biomarkers capable of predicting the course of RA in individual patients, as well as guiding therapeutic choices on the basis of specific pathobiological mechanisms [3]. In parallel, despite better control of disease activity, the burden of extra-articular manifestations and comorbidities remains high due to a multitude of factors, including ageing of the population, changes in lifestyle risk factors, and the role of nonclassical inflammatory drivers of damage, such as autoantibodies and other immune pathways [4, 5]. As a matter of fact, comorbidities rather than joint disease are major determinants of drug refractoriness and disability in many patients [4, 5].