Large vessel vasculitides (LVV), including giant cell arteritis (GCA) and Takayasu arteritis (TAK), share common features such as inflammation of large sized arteries but differ in several key aspects, including age of onset and pathogenic mechanism. This narrative review gives an update of recent insights into pathogenesis of GCA and TAK, and discusses emerging targeted therapies based on these insights. It highlights omics-based signatures, ULK3 and SLAMF7 in GCA, EGR1 in TAK, alongside genetic and somatic risk factors such as clonal haematopoiesis (DNMT3A/TET2) linked to relapse and ischaemic vision loss in GCA, and the IL6R-p.Asp358Ala variant as a predictor of reduced interleukin (IL)-6 receptor blockade response. Common mechanisms include CD4⁺ T-cell, monocyte/macrophage, and B-cell infiltration with activation of IL-6, JAK/STAT/interferon, and IL-17 pathways. Giant cell arteritis is characterised by GM-CSF-driven macrophages and disrupted programmed cell death (PD)-1/PD-L1 checkpoint regulation, while TAK shows dominance of CD8⁺ T cells and tumour necrosis factor (TNF)-α signalling. Interleukin-6 receptor inhibitors (e.g., tocilizumab) show robust efficacy in GCA but with notable non-responders; the JAK inhibitor upadacitinib demonstrated efficacy in a Phase III study, whereas IL-17 blockade (secukinumab) yielded inconsistent results. In TAK, TNF inhibitors and tocilizumab are comparably effective; early data suggest Janus kinases (JAK) inhibitors promote remission, imaging improvement, and glucocorticoid sparing. Mavrilimumab (GM-CSF receptor blockade) is promising in GCA. Recent studies have increasingly focused on short-term glucocorticoid therapy in combination with biologic agents. Advances in biomarker research, including investigation of the IL-6 receptor and IL-17A gene polymorphisms, may enable more targeted therapeutic strategies.
Reisch et al. (2026) studied this question.