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; however, many patients still fail to meet treatment objectives, leading to the recognition of clinical phenotypes that remain therapeutically challenging under the current treat-to-target standard of care, including preclinical inflammatory arthritis, late-onset RA, and treatment-resistant RA. Precision medicine approaches are beginning to characterize the pathogenesis of RA in such populations, and to inform effective tailoring of DMARD therapy to individual patients. Simultaneously, observational data derived from clinical practice are increasingly being used to understand the risks and benefits of long-term DMARD therapy under real-world conditions of use, with registries and other observational sources confirming long-term effectiveness, revising safety profiles, and estimating the costs of treatment for approved therapies. Together, these strategies offer opportunities to address unmet needs in the care of patients with RA. In this review of peer-reviewed clinical and translational research in RA, we identify several clinical phenotypes that demonstrate inadequate response to guideline-directed therapy and review frontiers in clinical research in RA emerging over the last decade, highlighting the use of precision medicine and real-world evidence-based approaches to advance individualized, patient-centered care.