Efficacy and safety of dual-targeted therapy with tofacitinib and TNF inhibitors in refractory spondyloarthritis: a case series from a tertiary care center

Spondyloarthritis (SpA) is a complex inflammatory disease involving multiple cytokine pathways, including tumor necrosis factor-α (TNF-α) and Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling. Despite advances in biologic and targeted synthetic therapies, up to 40% of patients with SpA remain refractory to monotherapy. This case series from a tertiary care center in India evaluated the efficacy and safety of dual-targeted therapy (DTT) combining tofacitinib, a JAK inhibitor, with TNF inhibitors in four patients with refractory SpA and psoriatic arthritis (PsA). All four patients had longstanding disease (mean duration 11.5 years) and had failed at least one prior biologic. Case 1 (PsA): Long-standing disease (24 years) failed optimized adalimumab; following DTT, disease activity in psoriatic arthritis (DAPSA) score improved from high disease activity (36) to low disease activity (8). Case 2 (SpA): Refractory to two TNF inhibitors; after adding tofacitinib, the Ankylosing Spondylitis Disease Activity Score incorporating C-reactive protein (ASDAS-CRP) score improved from very high activity (3.7) to low disease activity (1.7). Case 3 (SpA): Presented with very high ASDAS-CRP (3.8); rapid clinical response and laboratory remission (ASDAS-CRP, 1.6) were achieved within months of starting DTT. Case 4 (SpA): Failed adalimumab monotherapy; the addition of tofacitinib led to an improvement in ASDAS-CRP from 3.5 to 1.7. No serious adverse events or significant laboratory abnormalities were observed over 5–18 months. DTT combines extracellular TNF-α blockade with intracellular JAK-STAT inhibition. This addresses the pathway redundancy and compensatory mechanisms in refractory SpA. Our findings add to the emerging real-world evidence supporting DTT therapy as a promising option for patients with refractory SpA. Our real-world findings demonstrate improved disease control and safety when monotherapy fails. Future prospective studies are essential to optimize the selection, dosing, and long-term safety of DTT.