Metabolic Syndrome May Drive Treatment Resistance in Psoriatic Arthritis, Study Finds

Psoriatic arthritis is a chronic inflammatory condition often marked by joint pain, skin involvement, and a range of musculoskeletal symptoms such as enthesitis and dactylitis. While many patients respond well to current therapies, a subset faces persistent symptoms and poor therapeutic outcomes, termed the “difficult-to-treat” phenotype. This study aimed to examine whether metabolic dysfunction contributes to this challenging clinical profile.

The cross-sectional study was carried out at the Rheumatology Clinic of Fondazione Policlinico Campus Bio-Medico of Rome and involved 182 patients diagnosed with PsA. Disease activity and the presence of metabolic syndrome were assessed using established criteria. The D2T classification was based on modified definitions drawn from rheumatoid arthritis guidelines and adapted for PsA.

The key findings were as follows:

• 42.9% of the total psoriatic arthritis (PsA) cohort met the criteria for metabolic syndrome (MetS).
• Among patients with the difficult-to-treat (D2T) phenotype, 81.8% had comorbid MetS.
• In contrast, only 29.4% of patients in the non-D2T group had MetS.
• Statistical analysis showed a strong association between MetS and the D2T phenotype, with an odds ratio of 7.56.
• Patients with MetS were over seven times more likely to show treatment resistance.
• Path analysis confirmed MetS as an independent factor contributing to the development of the D2T phenotype.

These findings emphasize the role of metabolic health in influencing the course and severity of PsA. The authors emphasize that managing metabolic dysfunctions—such as obesity, hypertension, and insulin resistance—may be crucial in improving therapeutic response and reducing disease burden.

While the study provides valuable insight, the authors acknowledge certain limitations. These include reliance on D2T criteria adapted from rheumatoid arthritis, a single-center design, and the inability to capture certain variables like treatment adherence or patient-reported outcomes. Moreover, as a cross-sectional study, the data cannot establish causality between MetS and the D2T phenotype.

The research represents the first to establish a clear association between metabolic syndrome and treatment resistance in PsA. It suggests that integrated care approaches targeting both PsA and its metabolic comorbidities could enhance treatment outcomes. Strategies such as lifestyle modifications, interdisciplinary collaboration with metabolic specialists, and the use of therapies with minimal metabolic impact may offer a more effective path forward for patients facing this difficult-to-manage form of PsA.

The authors concluded, "Further studies are needed across diverse patient populations to confirm these findings and help refine clinical definitions and treatment pathways for D2T PsA."

Reference:

Damiano Currado, Francesca Trunfio, Francesca Saracino, Lyubomyra Kun, Annalisa Marino, Erika Corberi, Antonio Orlando, Ludovica Lamberti, Leonardo Frascà, Marta Gatti, Onorina Berardicurti, Marta Vomero, Vasiliki Liakouli, Roberto Giacomelli, Luca Navarini - Patients with psoriatic arthritis and comorbid metabolic syndrome show a difficult-to-treat phenotype: another mosaic tile in the definition of a still undefined subset of patients: RMD Open 2025;11:e005717.