SELECT-SWITCH is the first double-blind RCT to test mechanism-of-action switching (to the JAK inhibitor upadacitinib) versus cycling to a second TNF inhibitor (adalimumab) after a first TNFi fails in RA. At 12 weeks, upadacitinib roughly doubled low-disease-activity rates and beat adalimumab on the primary endpoint and 4 of 5 ranked secondaries — though HAQ-DI function did not separate and safety was comparable.
A 2026 clinical-pharmacology perspective arguing that biologic treatment failure in obesity is partly a pharmacokinetic problem: weight-driven clearance leaves many patients on fixed-dose subcutaneous biologics systematically underdosed, and dosing strategy should be matched to the weight–clearance relationship.
The 2025 EULAR update to the Behçet’s syndrome recommendations moves monoclonal TNF-alpha inhibitors (especially infliximab) to first-line induction and maintenance for eye, vascular and parenchymal-CNS disease, displacing cyclophosphamide and the azathioprine-first strategy, and broadens treatment targets to angiographic and endoscopic remission.