Obesity and fibromyalgia are associated with a difficult-to-manage psoriatic arthritis phenotype and adverse long-term outcomes

The concept of difficult-to-manage (D2M) psoriatic arthritis (PsA) has been recently proposed. Herein, we report on the prevalence, predictors and outcomes of D2M PsA. This is a prospective single-center cohort study of PsA patients initiating b/tsDMARDs from 01/01/2009 until 01/01/2025. The EULAR proposed definition for D2M PsA was applied. Baseline parameters were assessed as predictors of D2M development using multiple logistic regression models. Long-term outcomes were compared between D2M and non-D2M patients by evaluating functional progression and adverse event rates. During a median follow-up time of 3.4 years, 46/350 patients (13.1%) developed D2M disease. Compared with non-D2M, those with D2M had significantly higher baseline functional impairment ( p < 0.05), a greater burden of obesity, osteoarthritis and fibromyalgia ( p < 0.05) and no improvement in disease activity at 6 months ( p < 0.0001). Independent predictors of D2M PsA were fibromyalgia and obesity (OR 4.634 and 2.265, respectively; p < 0.05 for both), whereas the absence of multimorbidity was associated with a lower probability of developing D2M phenotype (adjusted odds ratio 0.416, p = 0.02). During 1630 patient-years of follow-up, D2M patients showed higher functional impairment, rates of serious adverse events and hospitalizations compared with non-D2M patients. Thirteen percent of PsA patients starting b/tsDMARDs developed D2M and had a worse prognosis compared with non-D2M subgroup. Fibromyalgia and obesity independently predicted progression to D2M. If confirmed in other cohorts, these findings could contribute to better characterization and improved therapeutic approaches for this subgroup of PsA patients.