At a EULAR 2025 session titled “What makes ‘Difficult-to-treat RA’ so difficult to treat? And what can we do?”, Drs. Paula David and Dennis McGonagle introduced the emerging concept of polyrefractory rheumatoid arthritis (RA), a term now being used to describe a subset of patients who have failed to respond to five or more biologic or targeted synthetic DMARDs. This new classification, derived from recent multinational registry data, represents a significant step in refining our understanding and management of the most treatment-resistant forms of RA.