Defining Clinical and Molecular Phenotypes of Multi-Drug Resistance in difficult to treat Rheumatoid Arthritis

Rheumatoid Arthritis (RA) is the most common, chronic, inflammatory joint disease with a prevalence of about 1% of the adult population (22M patients worldwide and 7M in EU) and estimated to be responsible for 10,000 disability adjusted life years (DALY's) costing EU society €55B annually. Despite aggressive therapy, about a third of patients have to give up work within 5 years of disease onset mainly due to lack of response to multiple disease modifying anti-rheumatic drugs (DMARDs), multi-drug resistance (MDR). Thus, the main objective of this proposal is to define the clinical and molecular phenotypes leading to MDR in RA patients to prevent when possible or, when not possible, optimise the management of these patients. MDR-RA is highly relevant to the program, as these patients are often disabled, unable to work and paying a high personal and societal burden. Moreover, MDR-RA is under-researched and the underlying pathobiological mechanisms for resistance remain unknown, while as we have no predictors of therapeutic response to any of currently available drugs, inevitably treatment is based on trial-and-error. MDR-RA has the ambition of transforming care for these patients and deliver significant advances beyond the state-of-the-art methodologies, as for the first time, molecular pathology will be integrated into clinical, psychosocial, pain perception and imaging profiling in existing clinical cohorts to develop truly holistic predictive models for future clinical use (iCare-RA). The transformative potential of iCare-RA will be tested in a prospective randomised trial in comparison with routine standard of care, while its future implementation potential will be assessed through an early economic modelling. Finally, a strong management and dissemination strategy will facilitate further advancing science in the field, beyond the duration of the project, and future adoption by patients, specialist professional bodies, policy makers and regulatory authorities.