Dual targeted therapy with biologic agents and small molecules in refractory inflammatory arthritis: clinical...

Biologic agents and small molecules have transformed the management of rheumatoid arthritis (RA), psoriatic arthritis (PsA), and spondyloarthritis (SpA). Nevertheless, some patients experience persistent, uncontrolled inflammation despite multiple targeted therapies. Evidence for dual targeted therapy (DTT) remains scarce. This study aims to describe the clinical characteristics, therapeutic rationale, and outcomes of patients with severe, multi-drug-refractory inflammatory arthritis and autoinflammatory disease treated with DTT. This clinical case series included patients with RA, PsA, FMF-associated SpA and Crohn's disease, SpA-associated atopic dermatitis, and one patient with TRAPS and PsA treated with DTT. Disease activity was evaluated using validated indices, physician assessment, patient-reported outcomes, and inflammatory markers. Safety was evaluated through clinical and laboratory monitoring. Eight patients received nine DTT courses. Mean follow-up was 11.7 ± 4.3 months. Median ESR decreased from 42 mm/h (IQR 34) to 16.1 mm/h (IQR 9), and mean CRP declined from 1.52 ± 0.55 mg/dL to 0.35 ± 0.24 mg/dL. Disease activity improved across all assessed indices. One patient with FMF-associated SpA and Crohn's disease required modification of DTT due to persistent intestinal activity and subsequently achieved remission. The prednisone dose decreased from 25 mg/day (IQR 12.5) to 2.5 mg/day (IQR 5). No adverse events were observed. DTT was associated with clinically meaningful improvements in refractory inflammatory arthritis and autoinflammatory disease, demonstrating a favourable safety profile and a clear steroid-sparing effect. These preliminary findings support its potential role in highly refractory settings, although larger studies are needed to define long-term safety and optimal therapeutic combinations.