Vladimir Tesar, Jan Miroslav Hartinger, Zdenka Hruskova
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引用次数: 0
Abstract
Introduction: ANCA-associated vasculitis (AAV) is a rare, life-threatening disease which may result in serious pulmonary and kidney damage. Cyclophosphamide or rituximab and high-dose glucocorticoids significantly improved patient outcomes, but at the expense of severe complications. Moreover, many patients still relapse and bear a significant burden of both disease- and treatment-related complications. Alternative complement pathway and C5a receptor signaling were demonstrated to play an important role in AAV pathogenesis. Avacopan is selective C5a receptor inhibitor successfully tested in renal AAV as glucocorticoid-sparing agent.
Areas covered: Pharmacokinetic/pharmacodynamic properties, clinical efficacy and safety of avacopan, available clinical trials and real-world experience with avacopan.
Expert opinion: In the phase 3 trial avacopan was shown to be non-inferior at six and superior at 12 months compared to high-dose glucocorticoids and either cyclophosphamide or rituximab in patients with active AAV. Treatment with avacopan was well tolerated and associated with improved quality of life. In patients with severe renal AAV, renal function improved more in avacopan-treated than in high-dose glucocorticoid-treated patients. Avacopan could thus replace high-dose glucocorticoids to avoid glucocorticoid-related toxicity and to improve long term renal outcome. As avacopan is CYP 3A4 inhibitor and substrate, drug-drug interactions must be considered during the treatment.
期刊介绍:
Advances in drug development technologies are yielding innovative new therapies, from potentially lifesaving medicines to lifestyle products. In recent years, however, the cost of developing new drugs has soared, and concerns over drug resistance and pharmacoeconomics have come to the fore. Adverse reactions experienced at the clinical trial level serve as a constant reminder of the importance of rigorous safety and toxicity testing. Furthermore the advent of pharmacogenomics and ‘individualized’ approaches to therapy will demand a fresh approach to drug evaluation and healthcare delivery.
Clinical Pharmacology provides an essential role in integrating the expertise of all of the specialists and players who are active in meeting such challenges in modern biomedical practice.