Novel Therapies in Takayasu Arteritis

Abstract

Takayasu Arteritis (TAK) is a large-vessel vasculitis that preferentially involves the aorta and its primary branches. Cardiac involvement is frequent in TAK and is a major determinant of the patient's outcome. Glucocorticoids (GC) are the mainstay of therapy for TAK, with high doses of GC effective to induce remission. However, relapses are common and lead to repeated and prolonged GC treatments with high risk of related adverse events. Potential GC toxicity is a major concern, especially because patients with TAK are young and need to be treated for several years, often for the whole life. Conventional immunosuppressive drugs are used in patients with severe manifestations but present some limitations. New therapeutic approaches are needed for patients with refractory disease or contraindications to conventional therapies. Fortunately, major progress has been made in understanding TAK pathogenesis, leading to the development of targeted biotherapies. In particular, IL-6 and TNF-α pathways seems to be the most promising therapeutic targets, with emerging data on Tocilizumab and TNF inhibitors. On the other hand, new insights on JAK-Inhibitors, Rituximab, Ustekinumab and Abatacept have been explored in recent studies. This review summarizes the emerging therapies used in TAK, focusing on the most recent studies on biologics and analyzing their efficacy and safety.

A rare imaging case: Takayasu arteritis

“…The treatment for TA focuses on controlling the inflammation that can lead to permanent damage to the organs and is divided in medical and surgical treatment [2,4] . Medical treatment involves using Prednisone, nonglucosteroidal therapies such as methotrexate, azathioprine, mycophenolate mofetil, cyclophosphamide; tumor necrosis factor inhibitors -etanercept, infliximab, and adalimumab; JAK-inhibitors such as Tofacitinib; Rituximab; Tocilizumab and Abatacept [7,8] . Revascularization procedures are necessary for irreversible vascular lesions that have a significant influence on hemodynamics [2] .…”

Extracellular Matrix Remodeling in Vascular Disease: Defining Its Regulators and Pathological Influence

“…There are a wide variety of human vasculitides which affect vessels of all sizes and involve the infiltration of the vessels with inflammatory cells including neutrophils, monocyte/macrophages, and lymphocytes, such as various T-cell subtypes. [199][200][201][202][203] The causative causes vary and include autoimmune reactions to vessel antigens from circulating antibodies or cytotoxic T cells, immune complex deposition, infections, drug reactions, and genetic mutations. Destruction of vessel walls occurs due to ECM degradation which can occur in the intimal, medial, or adventitial matrices in large-and mediumsized vessels and which can also be accompanied by cell loss due to destruction of ECs, VSMCs, or adventitial cells.…”

“…Vascular ECM Remodeling and Pathologic Influence hyperplasia, and luminal narrowing. 202 Some therapeutic successes have occurred with corticosteroids and more recently with blocking antibodies directed to TNFα or IL-6, where disease remissions can occur in some cases. 202 Kawasaki disease is a vasculitis that involves medium and small-sized vessels and has a predilection to involve the coronary arteries, with transmural inflammation involving monocyte/macrophages and activated T cells (both CD8 and CD4), and the development of aneurysms.…”

High-throughput sequencing reveals the change of TCR α chain CDR3 with Takayasu arteritis

“…In recent years, progress has been made in studying the pathogenesis of TAK, which has led to the development of targeted biotherapy. Among them, IL-6 and TNF-αare currently considered promising therapeutic targets [11,12]. In addition, new insights into JAK inhibitors, rituximab, and other drugs have been reported continuously [13][14][15].…”