髙田 秀人
   Department   School of Medicine(Tokyo Women's Medical University Hospital), School of Medicine
   Position   Assistant Professor
Article types Review article
Language English
Peer review Non peer reviewed
Title Molecular targeted therapies for microscopic polyangiitis and granulomatosis with polyangiitis.
Journal Formal name:The Korean journal of internal medicine
Abbreviation:Korean J Intern Med
ISSN code:20056648/12263303
Domestic / ForeginForegin
Volume, Issue, Page 34(3),pp.492-503
Author and coauthor Harigai Masayoshi, Tsutsumino Michi, Takada Hideto, Nagasaka Kenji
Publication date 2019/05
Summary Clinical trials and observational studies have established cyclophosphamide (CY) or rituximab plus glucocorticoid (GC) as standard remission induction therapies in patients with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA). However, because these regimens are associated with serious adverse drug reactions, the development of drugs with novel mechanisms of actions are needed. Progress in basic and clinical research has identified novel candidate targeting molecules, including B-cell activating factor (BAF), C5a receptor, and interleukin-6. The combination of rituximab and BAF blockade in patients with MPA and GPA is under investigation in an effort to strike a better benefit-risk balance. Phase II clinical trials of avacopan (CCX168), an orally administered C5a receptor antagonist, have suggested a reduction in the dosage of concomitant GC or the replacement of GC in patients with MPA and GPA. The results from a currently ongoing phase III trial are awaited. Anecdotal case reports and an open-label pilot study have indicated the effectiveness of tocilizumab in patients with MPA and GPA. A randomized clinical trial comparing tocilizumab and intravenous CY in combination with GC is currently in progress. Molecular targeted therapy is expected to transform the treatment strategy for MPA and GPA to allow GC-free or at least less GC-dependent forms of therapy.
DOI 10.3904/kjim.2018.366
PMID 30613065