Dual Targeted Therapy as a Treatment Strategy for Refractory Psoriatic Arthritis: Real-World Effectiveness and Safety From a Prospective Cohort.

OBJECTIVE

To describe patient profiles, treatment patterns, clinical outcomes, and safety of intentional dual biologic or targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD) therapy in psoriatic arthritis (PsA). A subset of patients with PsA continue to experience persistent inflammation despite b/tsDMARD monotherapy. Dual b/tsDMARD therapy has emerged as a potential strategy in refractory cases, but evidence in PsA remains limited.

METHODS

We conducted a nested study within the International Psoriasis and Arthritis Research Team prospective cohort. Adults satisfying Classification Criteria for Psoriatic Arthritis who received two concurrent b/tsDMARDs (TNFi, IL-17i, IL-23i, JAKi, TYK2i, with or without apremilast) for ≥60 days were included. Baseline features, previous therapies, indications for dual therapy, and disease activity measures (tender joint count in 68 joints, swollen joint count in 66 joints, Disease Activity Index for Psoriatic Arthritis [DAPSA], Psoriasis Area and Severity Index [PASI], body surface area, patient visual analog scale) were collected. Clinical outcomes were reassessed at three- to six-month intervals, with effectiveness assessed only for dual bDMARD + JAK/TYK2i combinations. Safety was evaluated through all-cause adverse events.

RESULTS

Thirty-nine patients initiated dual therapy: 24 patients received bDMARD + JAK/TYK2i and 15 patients with bDMARD + apremilast. Patients were highly treatment-experienced (median two conventional synthetic DMARDs and five b/tsDMARDs). Indications included refractory peripheral arthritis, concurrent joint and skin activity, palmoplantar or nail psoriasis, and persistent enthesitis. Among bDMARD + JAK/TYK2i combinations, improvements were observed in joint counts, DAPSA, PASI, and patient-reported outcomes. Adverse events were infrequent and mild.

CONCLUSIONS

In this real-world cohort, dual b/tsDMARD therapy was feasible, well-tolerated, and associated with clinical improvement in patients with refractory PsA. These findings support its individualized use and highlight the need for controlled studies to define long-term safety and optimal combination strategies.