Current Therapies for ANCA-Associated Vasculitis

Abstract

The ANCA-associated vasculitides, granulomatosis with polyangiitis (GPA, formerly Wegener's), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA, formerly Churg-Strauss), are a group of multisystem autoimmune diseases characterized by necrotizing small- to medium-vessel vasculitis and the presence of anti-neutrophil cytoplasmic antibodies. Current therapeutic strategies consist of glucocorticoids in conjunction with either conventional or biologic agents for both induction of remission and remission maintenance. Treatment goals include reducing toxicity of induction therapy, preventing disease relapse, and limiting overall accrual of both disease-related damage and treatment-related morbidity. Future research directions include investigation of the optimal duration and frequency of maintenance therapy as well as development of targeted therapeutic agents, which is enhanced by emerging insights into disease pathogenesis.

Granulomatosis with polyangiitis (Wegener's disease): An updated review of ocular disease manifestations

“…Azathioprine has shown some success, but it is less effective than cyclophosphamide and should only be considered in patients experiencing adverse side effects or when fertility concerns arise (80). Methotrexate has been used in patients with limited GPA, though it is less likely to achieve and sustain remission (81,82). Recently, trials confirmed that B cell depletion with rituximab were comparable to cyclophosphamide as part of induction therapy for active ANCA-associated vasculitis and with possibly superior performance in relapsing disease (83,84).…”

Critical updates in the 7th edition of the American Society for Apheresis guidelines

“…Most patients only experience periodic symptoms of vasculitis and recover with minimal treatment. Patients with severe organ involvement (kidney, brain, GI tract, heart) exhibit >10% weight loss, and patients over 50 years old may require continuous therapy …”

“…In 2005, Guillevin et al reported a case series of 115 patients with HBV‐PAN that received TPE, immunosuppression, and/or anti‐viral medication; ∼81% of the patients recovered . In sharp contrast, TPE in idiopathic PAN has not proven beneficial compared to steroids, and is therefore a category IV indication . Although TPE has not been shown to be superior to steroids alone in EPGA, it remains part of the EPGA Consensus Task Force recommendations, especially for those with ANCA and rapidly progressive glomerulonephritis (RPGN) or pulmonary renal syndrome (e.g., Wegener's disease) .…”

“…Patients with severe organ involvement (kidney, brain, GI tract, heart) exhibit >10% weight loss, and patients over 50 years old may require continuous therapy. 10,156,159,160 Thus far, the highest success with TPE has been reported in cases with HBV-PAN, which is a category II indication. TPE is performed to remove the immune complexes, and is often used in conjunction with steroids and anti-viral medications.…”

Innovative human-specific investigational approaches to autoimmune disease

“…Multiple mechanisms contributing to loss of tolerance to the self-antigens have been Both lack of understanding of the human disease, which can be contributed at least in part to inadequate preclinical model systems, and the relative rarity of AAV, hamper progress towards development of targeted therapies and reliable (companion) diagnostics (36).…”