Emerging Therapies in Antineutrophil Cytoplasm Antibody-Associated Vasculitis

Shunsuke Furuta; David Jayne


Curr Opin Rheumatol. 2014;26(1):1-6. 

In This Article

Abstract and Introduction


Purpose of review The current standard therapy for antineutrophil cytoplasm antibody-associated vasculitis (AAV), high-dose glucocorticoid and cyclophosphamide followed by azathioprine, has improved the disease prognosis. However, there are still unmet needs. For example, reducing relapse risk and glucocorticoid toxicity. Newer therapies are needed.

Recent findings Potential newer drugs are emerging following a better understanding of disease mechanisms and the availability of targeted therapies to B cells, T cells, proinflammatory cytokines and complement. Rituximab, an anti-CD20 monoclonal antibody, has proven efficacy in remission induction therapy for AAV, and two trials with rituximab as remission maintenance therapy are ongoing. Clinical trials evaluating mycophenolate mofetil as remission induction therapy, gusperimus, belimumab and complement factor C5a inhibition are also ongoing, and many other potential candidates are being investigated both clinically and experimentally.

Summary B-cell therapy is now an established treatment in AAV and several other therapies are under evaluation. However, the unmet need in vasculitis therapy remains large and newer therapies either alone or in combination will need to both improve efficacy and permit reductions in glucocorticoid and immunosuppressive exposure.


Antineutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) is a group of vasculitides characterized by small to medium-sized blood vessel vasculitis and the presence of ANCA. AAV includes microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA, Wegener's granulomatosis) and eosinophilic granulomatosis with polyangiitis (EGPA, Churg–Strauss syndrome). AAV is a life-threatening disease and the mortality is 80% at 1 year in untreated patients.[1] The previous clinical trials for the induction and maintenance of remission of AAV have led to the current standard therapy with the combination of high-dose glucocorticoids and cyclophosphamide for remission induction followed by azathioprine or methotrexate maintenance therapy.[2,3] This approach has high remission rates of 80–90% and has reduced mortality to 25% at 5 years but many patients will relapse and long-term therapy is required. These therapies are associated with early and late toxicity that contribute to the increased mortality risk and vital organ damage suffered by vasculitis patients. In addition, despite maintenance therapy at least 10% of patients relapse each year.[4] Reducing glucocorticoid exposure is now a major unmet need in order to reduce infection rates, cardiovascular risk and other side-effects reducing patients' quality of life. The role of glucocorticoids in relapse prevention is unclear, with variance in clinical practice and a meta-analysis suggesting glucocorticoid withdrawal increased relapse rates.[5] Thus, newer therapies are needed (Table 1).

Although the cause of AAV is not fully understood, abnormalities of components of the immune system such as B cells, T cells, neutrophils and complement (specially, the alternative pathway) are observed in AAV. B-cell depletion with rituximab is now a licensed therapy for AAV and other potential drugs are emerging, with more targeted modes of action than conventional immunosuppressants.