Clinical and imaging characteristics of difficult-to-treat patients with rheumatoid arthritis and peripheral psoriatic arthritis with ultrasound-confirmed inflammation

To evaluate the proportion of Difficult To Treat (D2T) disease according to three operational definitions in a population of Rheumatoid Arthritis (RA) and peripheral Psoriatic Arthritis (PsA) with ultrasound (US)-confirmed inflammation, and to characterize its clinical, structural, and therapeutic features. Cross-sectional study involving RA or peripheral PsA who had active disease, established through both clinical and US examination. D2T disease was categorized according to three criteria: an operational treatment-failure-based D2T definition, requiring inadequate response or failure to ≥ 1 csDMARD and ≥ 2 b/tsDMARDs with different mechanisms of action (MOAs); a time-dependent criterion, defined by failure to ≥ 1 csDMARD and two or more b/tsDMARDs with different MOAs over a period of less than 12 months and a very refractory criterion, requiring failure to ≥ 1 csDMARD and ≥​ 3 b/tsDMARDs with different MOAs. A total of 148 patients were included. Overall, 31.7% fulfilled the treatment-failure-based D2T definition, 12.1% the time-based definition, and 18.2% the very refractory one. Treatment-failure-based D2T disease was more frequent in RA ( p = 0.033) and associated with longer disease duration ( p < 0.001), cardiovascular comorbidity ( p = 0.037), US proliferative synovitis ( p = 0.034), erosive disease ( p < 0.001), combined therapy (csDMARD + b/tsDMARD) ( p < 0.001), and prior tsDMARD ( p < 0.001). Time-based D2T disease was equally present in both RA and PsA, associated with combined therapy ( p = 0.008), tsDMARD use ( p = 0.002), and nail involvement ( p = 0.019). Very refractory D2T disease was more prevalent in RA ( p = 0.029) and associated with longer disease duration ( p = 0.014), erosive disease ( p < 0.001), US proliferative synovitis ( p = 0.046), combined therapy ( p = 0.003), and tsDMARD exposure ( p < 0.001). D2T disease defines a severe phenotype characterized by cumulative disease burden, structural damage, comorbidities, and treatment refractoriness. Erosive disease, combined therapy, and tsDMARD exposure emerged as associated factors across definitions, emphasizing early disease control and comprehensive management.