Frontiers in Rheumatoid Arthritis: Emerging Research and Unmet Needs in Pharmacologic Management

The management of rheumatoid arthritis (RA) has undergone several practice-defining evolutions, beginning with the approval of low dose methotrexate and continuing through the introduction of numerous disease-modifying antirheumatic drugs (DMARDs). With increasing capability to target pro-inflammatory pathways, successive therapeutics have carried the promise of improved disease control for patients with RA. Despite an expanding arsenal of therapeutics for RA, many patients fail to meet treatment objectives, leading to the recognition of several clinical phenotypes that remain therapeutically challenging under the current treat-to-target standard of care. These include both individuals with preclinical inflammatory arthritis as well as extensively treatment-experienced patients with refractory disease. Using precision medicine approaches to better characterize the pathogenesis of RA in such populations can help inform effective tailoring of DMARD therapy to individual patients. Simultaneously, observational data derived from clinical practice is increasingly being used to understand the risks and benefits of long-term DMARD therapy under real-world conditions of use. Together, these strategies offer opportunities to address unmet needs in the care of patients with RA. In this review, we identify several clinical RA phenotypes that demonstrate inadequate response to guideline-directed therapy and review frontiers in clinical research in RA, highlighting the use of precision medicine and real-world evidence-based approaches to advance individualized, patient-centered care.