Rheumatology

Non-TNFi biologics in RA and RA-ILD: higher pneumonia and mortality at similar ILD risk

This nationwide Korean cohort included 26,120 RA patients, with 641 RA-ILD cases and 209,852 treatment episodes across csDMARDs and advanced therapies. Adjusted ILD incidence and ILD-related hospitalizations were similar across TNFi, non-TNFi biologics, JAK inhibitors, and csDMARDs, including in RA-ILD. Non-TNFi biologics were associated with higher risks of hospitalization, serious infection, and all-cause mortality versus csDMARDs in both RA and RA-ILD. Pneumonia-related hospitalizations and recurrences were consistently higher with non-TNFi biologics, whereas TNFi and JAK inhibitors showed no such signal. MACE risk did not differ across DMARD classes, underscoring pneumonia and infection as the main safety concern with non-TNFi biologics. 1

GCA markedly raises aortic and vascular event risk beyond background comorbidity

This French nationwide study followed 23,193 incident GCA patients aged at least 50 years, matched to general and hospitalized cohorts. Compared with the general population, GCA patients had markedly higher risks of aortic events, MACE, PAD, and visceral artery events. Versus a comorbidity-matched hospitalized cohort, risks of aortic, PAD, and visceral artery events remained elevated, while MACE risk was similar. Periods of active GCA were associated with nearly doubled MACE risk, linking inflammatory activity to major cardiovascular events. These findings support aggressive control of GCA activity, systematic cardiovascular risk management, and selective large-vessel imaging surveillance. 2

Brain–sympathetic circuit restrains articular cartilage regeneration in osteoarthritis

This mechanistic study mapped a brain–cartilage circuit regulating joint cartilage regeneration in human and mouse osteoarthritis models. Activity in the hypothalamic paraventricular nucleus correlated with OA symptom burden and synovial fluid norepinephrine levels in patients. Tracing and neuromodulation experiments revealed a PVNCRH–sympathetic synovial nerve circuit that limits regeneration via norepinephrine signaling through β2-adrenergic receptors (ADRB2) on Proteoglycan 4+ cells. Inhibiting this circuit favored formation of stable mature articular cartilage instead of fibrocartilage, enhancing regeneration in experimental models. An ADRB2 inverse agonist prevented degradation in human cartilage explants, suggesting neuromodulatory and adrenergic targets for disease-modifying OA strategies. 3