Pathophysiology of large vessel vasculitis and utility of interleukin-6 inhibition therapy

Takayasu arteritis (TAK) and giant cell arteritis (GCA) affect mainly large- and medium-sized arteries. In refractory cases, vascular remodeling progresses and leads to serious outcomes. Studies have demonstrated that cytokines such as interleukin (IL)-6 play crucial roles in the pathophysiology of TAK and GCA. Recently, randomized controlled trials on IL-6 inhibition therapy using tocilizumab (TCZ) were performed, and significant effects were exhibited. The purposes of conventional treatments have been to improve symptoms and decrease the levels of inflammatory markers. Arterial changes have been considered as damages. However, after TCZ came into practical use, establishment of treat to target is desired to prevent vascular remodeling. In contrast, a combination therapy of glucocorticoids (GCs) and TCZ notably increases the risk of infections. When TCZ is used, careful attention must be paid to possible infections, and dose of GC should be tapered as much as possible. Future tasks are to establish indication and dosage of TCZ, indication for discontinuation of TCZ due to remission, efficacy of TCZ monotherapy, and protocols of TCZ for pediatric cases.