Therapy for ANCA-Associated Vasculitis

Introduction

Antineutrophil cytoplasm antibody (ANCA)-associated vasculitides are multisystem disorders of unknown etiology associated with circulating autoantibodies and characterized by inflammation and necrosis of small- and medium-sized arteries. ANCAassociated vasculitis (AAV) includes the distinct syndromes of Wegener's granulomatosis (WG), Churg–Strauss syndrome (CSS), and microscopic polyangiitis (MPA). Vasculitic disease, which may manifest by crescentic glomerulonephritis, and alveolar hemorrhage, is frequently found in WG and MPA. Patients with vasculitic manifestations of disease are usually ANCA positive (>90% of patients). WG is associated with ANCA directed at proteinase 3 (PR3), a serine protease, but the common target for ANCA in MPA and CSS is myeloperoxidase (MPO). WG and CSS are frequently associated with granulomatous disease. In WG, localized granulomatous disease may precede the vasculitic phase of disease. However, in a small percentage of patients, the localized form of disease may remain persistent. Asthma precedes vasculitic manifestations of CSS in >90% of patients and eosinophilia is frequently found. ANCA is less commonly detectable in CSS with 40% of patients being positive for MPO-ANCA; however, these patients are more likely to have vasculitis. In 1994, the Chapel Hill consensus conference recommended classifications for WG, CSS, and MPA. These were intended to be used as useful descriptions of disease for research to ensure homogeneity in clinical trials, rather than as diagnostic criteria.

Abstract

The potential therapies for antineutrophil cytoplasm antibody-associated vasculitis (AAV) have increased over the past 10 years. The aims of therapy are to induce remission of disease, maintain remission, and prevent relapse. Cyclophosphamide and glucocorticoids remain the standard therapy, but the toxicity of cyclophosphamide limits its use, and it is now confined to induction of remission and treatment of relapses. Newer biological agents show promise. Results of clinical trials with rituximab suggest that rituximab is as efficacious as cyclophosphamide; however, long-term outcome data are awaited. Other agents, such as azathioprine, are considered more appropriate for remission maintenance. Induction therapies should be tailored to the severity of the disease, with more aggressive treatments reserved for severe disease, as suggested by the BSR and BHPR guidelines and EULAR recommendations. The adverse events associated with the different therapies need to be borne in mind by clinicians when selecting the appropriate type, dose, and duration of treatment in AAV. As the understanding of the pathogenesis of AAV increases, new targets for treatment have been identified. Alongside this, a change in the approach to management is needed as patients are surviving their acute disease but suffer morbidity due to disease and treatment-related damage.

Keywords

treatment, ANCA, vasculitis