**1. Introduction**

Vasculitis is the general term used to describe diseases associated with inflammation of the blood vessels. This inflammation results in end-organ ischemia and damage with lifethreatening consequences. Treatment is tailored to the type of vasculitis the patient has, prognostic features and disease severity. Two main treatment phases are recognized: induction of remission, and maintenance of remission. In this chapter we will focus on the treatment of ANCA-associated vasculitis (AAV), namely: Granulomatosis with polyangiitis (GPA), formerly Wegener's Granulomatosis; Eosinophilic granulomatosis with polyangiitis (EGPA), formerly Churg-Strauss Syndrome, and Microscopic Polyangiitis (MPA). Patients with Polyarteritis nodosa (PAN) were included in the initial therapeutic trials of these diseases, therefore some of the studies results have been applied to that population as well.

We introduce first the historical use of glucocorticoids, which are uniformly incorporated in the treatment protocols of therapeutic trials. Cyclophosphamide is recommended for the induction of remission in AAV, and in particular for generalized and severe disease. CY‐ CLOPS, a trial of oral versus intravenous cyclophosphamide, demonstrated that intravenous dosing was as effective in inducing remission with a reduced cumulative dose, and with fewer episodes of leucopenia, but in long-term follow-up relapse was more common in the intrave‐ nous treatment group. NORAM compared the use of methotrexate compared to oral cyclo‐ phosphamide for induction of remission in patients with limited GPA, and concluded that methotrexate was nearly as effective as cyclosphosphamide in achieving remission, but in long-term follow-up more corticosteroids and further immunosuppressive agents were required. More recently, rituximab use for the induction of remission was studied in the RAVE and RITUXVAS clinical trials. Rituximab was proven to be effective as cyclophosphamide, but without a reduction in the rate of infection as had been expected. Plasma exchange in combi‐ nation with oral cyclophosphamide for patients with severe renal involvement significantly decreases the risk of end-stage renal disease compared to intravenous steroids and oral cyclophosphamide, but without a significant difference in patient survival.

© 2013 Fifi-Mah and Barnabe; licensee InTech. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2013 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Maintenance of remission is typically with oral cyclophosphamide, azathioprine or metho‐ trexate, with demonstrated efficacy in the CYCAZAREM and WEGENT studies. Leflunomide is also effective, and mycophenolate mofetil is less effective than azathioprine but is an alternative agent should the others not be tolerated. Etanercept therapy does not have a role in maintenance therapy given its inefficacy and toxicity in patients exposed to cyclophospha‐ mide. Other anti-TNF agents, rituximab, Intravenous Immunoglobulin (IVIg), 15-Deoxysper‐ gualin, antithymocyte globulin and alemtuzumab (CAMPATH-1H) have shown some benefit for refractory or relapsing disease and require further evaluation.

a relapse within 5 years despite treatment) [9] treatment protocols have reflected the need to obtain rapid control of disease activity and maintain long-term immunosuppression while reducing drug toxicity. This is the basis for an induction phase of treatment to achieve remission followed by a maintenance phase to reduce the risk of relapse. Guille‐ vin et al. developed the Five Factor Score [10] to identify factors associated with poor prognosis at the time of diagnosis. They initially analysed 342 patients with MPA, EGPA and PAN, and the five factors associated with increased mortality were: renal failure with creatinine greater than 140 μmol/L, proteinuria greater than 1 gram/day, cardiac involve‐ ment, central nervous system involvement, or severe gastro-intestinal involvement. In patients with none of these features, the 5 year survival rate was 88.1%. With 1 of these features, the 5 year survival rate declined to 74.1%, and with 2 or more of these features the survival rate was only 54.1%. The analysis of a larger group of 1108 patients with GPA, MPA, EGPA and PAN in 2009 [11] resulted in the identification of new prognosis factors associated with an increase in 5-year mortality rate. These include age > 65 years, cardiac involvement, gastro-intestinal involvement, and renal failure with creatinine >150 μmol/L. The presence of ear, nose and throat symptoms in patients with GPA and EGPA is

Treatment of ANCA-Associated Vasculitis in Adults

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**4. Categorization of disease severity to guide initial treatment agent**

Localised Upper and/or lower respiratory tract disease without any other systemic involvement or

Generalised Renal or other organ threatening disease, serum creatinine <500 μmol/liter (5.6 mg/dl)

**Table 1.** Categorization of disease severity to guide initial treatment in anti-neutrophilic cytoplasmic antibodies

We will now review in detail the evidence for the agents recommended in these treatment

Severe Renal or other vital organ failure, serum creatinine "/>500 μmol/litre (5.6 mg/dl)

Refractory Progressive disease unresponsive to glucocorticoids and cyclophosphamide

guidelines, as well as new evidence arising since their development.

As reflected in the European League Against Rheumatism (EULAR) treatment guidelines [12] the initial immunosuppressive agent choice is dictated by the extent and severity of the disease. The European Vasculitis Study (EUVAS) disease categorisation [13] separates disease severity into localized disease, early systemic disease, generalized, severe and

associated with a lower relative risk of death.

constitutional symptoms

Early Systemic Any, without organ-threatening or life-threatening disease

refractory disease.

**Category Definition**

(ANCA)-associated vasculitis [13]

We conclude the chapter by discussing the use of trimethoprim-sulfamethoxazole (T/S) use in localized disease, as well as a specific focus on the treatment evidence in EGPA with and without poor prognostic factors.
