Emerging Therapies in Antineutrophil Cytoplasm Antibody-Associated Vasculitis

Shunsuke Furuta; David Jayne


Curr Opin Rheumatol. 2014;26(1):1-6. 

In This Article

Future Direction of the Therapies for Antibody-Associated Vasculitis

The availability of targeted therapies, especially therapeutic antibodies and improved understanding of pathogenesis are providing new opportunities in vasculitis therapy. Consensus over disease definitions and subgrouping and the development of disease assessment tools and trial end-points have permitted the design and conduct of successful randomized controlled trials, difficult in rare, multisystem diseases. Reducing the toxicity of therapy is a major goal likely to be achieved with safer, more specific therapies. Although the RAVE and RITUXVAS trials did not demonstrate a safety benefit, the high level of efficacy of rituximab is inspiring regimens with reduced glucocorticoid exposure.

With evidence from a genome wide association survey,[48] indicating quite different genetic predisposition between PR3 and MPO-ANCA vasculitis and the evidence from trials that PR3-ANCA is an independent factor for relapse,[4] future studies may focus on separate serological subgroups. Also, subanalysis of the RAVE trial showed PR3-ANCA positivity was associated with early recurrence and persistence of severe disease.[49] As to remission maintenance therapy, optimal use of glucocorticoid, immunosuppressants and biologics may be different between PR3-/MPO-ANCA positive patients. From the clinical trial point of view, much of the recent progress in this field has developed from the creation of international collaborative networks permitting consensus approaches and large-scale clinical studies. Further development of these networks in both scale and quality is expected.

In addition to the main therapies, development of supportive therapies is also important in the treatment for AAV (e.g. bone and infection prophylaxis, renal replacement therapy). Although dialysis and renal transplantation have already been established for renal failure, severe respiratory failure is more difficult to manage and still can cause death. Recently there is more use of extracorporeal membrane oxygenation (ECMO) for acute respiratory failure including alveolar hemorrhage by AAV, and ECMO is useful.[50] However treatment options for chronic progressive pulmonary fibrosis in some AAV, especially MPA, remain poor. Pirfenidone is an antifibrotic drug licensed for idiopathic pulmonary fibrosis, but currently is not widely used because of its mild efficacy compared with severe side-effects such as photosensitivity. Development of regenerative medicine using embryonic stem (ES) cells and induced pluripotent stem (iPS) cells appears promising, though its clinical application is just commencing.