Frequency of complex-to-manage, difficult-to-manage and treatment-refractory psoriatic arthritis: applying the 2025 GRAPPA and EULAR definitions in a real-world longitudinal PsA cohort
Gonul Hazal Koc, Marc R Kok, Selinde V J Snoeck Henkemans, Jolanda J Luime, Ilja Tchetverikov, Lindy A Korswagen, Natasja H A M Denissen, Yvonne P M Goekoop-Ruiterman, Paul Baudoin, Petra Kok, Reinhard Bos, Radboud J E M Dolhain, Fabian Proft, Marijn VisObjectives
To determine the frequency and baseline characteristic differences of complex-to-manage (C2M), difficult-to-manage (D2M) and treatment-refractory (TR) psoriatic arthritis (PsA) in a real-world longitudinal cohort, using the recently proposed 2025 Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) and the European Alliance of Associations for Rheumatology (EULAR) definitions.
Methods
We analysed data from newly diagnosed, disease-modifying antirheumatic drug-naïve patients with PsA enrolled in the Dutch Southwest Early Psoriatic Arthritis cohort between 2013 and 2023. Patients were classified using the 2025 GRAPPA (C2M, TR) and EULAR (D2M, TR) PsA definitions. Frequencies were calculated for each definition. Time-to-event analyses using Kaplan-Meier methods assessed the timing of definition fulfilment and individual components. Longitudinal differences in patient-reported outcomes (PROs) were assessed using linear mixed-effects models.
Results
Among 885 newly diagnosed patients with PsA, 20% (179/885) fulfilled the GRAPPA-C2M definition, 4.2% (37/885) fulfilled the EULAR-D2M definition, 3.8% (34/885) met the EULAR-TR and 1.2% (11/885) fulfilled the GRAPPA-TR criteria definition during follow-up. Female sex, higher body mass index (BMI), longer symptom duration, presence of enthesitis and greater skin involvement differed with meeting definitions at baseline. Patients classified as GRAPPA-C2M, GRAPPA-TR, EULAR-D2M and EULAR-TR consistently reported worse long-term PROs (Health Assessment Questionnaire-Disability Index scores in C2M (β=0.17, 95% CI 0.10 to 0.24), GRAPPA-TR (β=0.37, 95% CI 0.22 to 0.51), EULAR-D2M (β=0.36, 95% CI 0.20 to 0.48) and EULAR-TR (β=0.40, 95% CI 0.25 to 0.55)).
Conclusions
Approximately 20% of patients with early PsA fulfilled the GRAPPA-C2M criteria, representing the earliest and broadest subgroup, while 4% met EULAR-D2M/EULAR-TR and 1.2% GRAPPA-TR definitions. These latter subgroups were more likely to be female, had higher BMI, greater skin involvement and enthesitis and experienced persistently worse PROs, underscoring the need for tailored management strategies.