Real-World Performance of GRAPPA and EULAR Definitions of Difficult-to-Treat (D2T) Psoriatic Arthritis: Insights from the ORCHESTRA Cohort

Objectives Psoriatic arthritis (PsA) is a complex inflammatory disease with significant musculoskeletal, dermatological, and comorbidity burden. Despite therapeutic advances, many patients remain difficult to treat. Conventional definitions often overlook distinctions between inflammatory and non-inflammatory drivers, risking inappropriate treatment escalation. Two consensus frameworks—the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) and the European Alliance of Associations for Rheumatology (EULAR)—have recently been proposed to better capture this complexity and differentiate true inflammatory refractoriness from non-inflammatory causes.[1,2] In this study, we aim to evaluate the applicability, overlap, and clinical utility of GRAPPA and EULAR definitions for complex/difficult-to-manage (C2M/D2M) and treatment-refractory PsA (TrPsA) in a real-world cohort. Methods We applied GRAPPA and EULAR frameworks to 76 PsA patients from the Ottawa Rheumatology CompreHEnSive TReatment and Assessment (ORCHESTRA) cohort, which includes patients with inflammatory arthritis initiating a new advanced therapy. Patients were categorized into broader groups, C2M-PsA (GRAPPA) and D2M-PsA (EULAR), and narrower inflammation-based subsets, TrPsA under GRAPPA and EULAR. Disease characteristics and Minimal Disease Activity (MDA) outcomes were assessed at 3 and 6 months. Results GRAPPA identified more patients as C2M-PsA (38/76; 50%) than EULAR’s D2M-PsA (17/76; 22.4%), reflecting broader inclusion. All D2M cases were encompassed within C2M, while GRAPPA uniquely identified 21 patients (Table). TrPsA classification showed near-perfect agreement (κ = 0.917). No significant MDA differences were observed across definitions, though within GRAPPA, inflammatory TrPsA showed numerically higher MDA rates. Non-articular domains (dactylitis, nail/skin psoriasis) were more frequently captured in the broader C2M/D2M than in the inflammatory subsets. Table 1. Summary of proposed definitions for C2M/D2M and TrPsA according to GRAPPA and EULAR frameworks, and patients’ prevalence per definition. Conclusion Applying EULAR and GRAPPA definitions in a real-world PsA cohort revealed complementary strengths: GRAPPA’s inclusiveness vs EULAR’s selectivity. Evaluating both across real-world and research settings will aid harmonization and validation of D2T-PsA frameworks. Integrating imaging-based models such as Persistent Inflammatory PsA (PiPsA) and Non-Inflammatory PsA (NiPsA) may further refine precision and clinical relevance. References [1.] Marzo-Ortega H. Ann Rheum Dis 2025;84:10.1016/j. ard.2025.10.002. [2.] Proft F. Ann Rheum Dis 2025;84:143-5.