Difficult to treat disease in psoriatic arthritis- is it different from axial spondyloarthritis?

Despite major therapeutic advances, a substantial proportion of patients with spondyloarthritis (SpA), including psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA), experience persistent symptoms, functional limitations, and reduced quality of life. Historically, heterogeneous terminology has limited comparability across studies for this population. To address this gap, three international initiatives, GRAPPA, EULAR, and ASAS, have proposed consensus definitions for two nested states: a broad category of "difficult-to-manage" (D2M) or "complex-to-manage" (C2M) disease and a more stringent "treatment-refractory" (TR) subset requiring objective inflammation and multi-mechanism therapeutic failure. This review synthesises these frameworks, highlighting shared principles and key differences. While all definitions adopt a dual-tiered structure, PsA-specific definitions reflect its multidomain nature, incorporating peripheral joints, entheses, skin, nails, axial involvement, and comorbidities; conversely, axSpA definitions are axial-centric, while other domains may play a role in determining D2M/TD disease as well. These distinctions have implications for trial design, biomarker discovery, and management strategies. Harmonisation, prospective validation, and biomarker-driven stratification remain essential to optimise outcomes and advance precision medicine.