The type of vasculitis and the extent of organ involvement guide treatment. The intensity of initial immunosuppression depends on the severity of organ involvement and the size of the vessels involved (Table 4.1). Therefore, an important part of treatment planning involves the assessment of organ involvement and its severity. Treatment may be divided into remission induction, maintenance, and long-term follow-up. Guidelines on the management of the vasculitides have been recently published [1–3]. In this chapter, we will cover the general principles of treatment and the agents used.

Remission induction covers the period of treatment from the initiation of therapy to remission. The choice of remission induction treatment depends on the severity of organ involvement and the size of the vessels involved (Table 4.1).

Long-term maintenance therapy is mainly required for patients with AAV. Current clinical practice considers possible transfer to maintenance therapy as early as 3 months and aims for a maximum duration of CYC therapy of 6–12 months when successful remission has been achieved [4].

In patients with AAV who have achieved successful remission (usually between 3 and 6 months), cyclophosphamide should be withdrawn and substituted with either azathioprine in combination with oral steroids [4, 5]. Methotrexate, mycophenolate or leflunomide may be used as alternatives for intolerance or lack of efficacy of AZA. Azathioprine is the conventional choice for remission maintenance. Methotrexate, mycophenolate and leflunomide have not been shown to be superior to azathioprine and should be considered in azathioprine-intolerant patients. The role and optimum regimen for rituximab during maintenance is currently being evaluated, initial data suggests a role for 6 monthly infusion over a 2 year period (Mainritsan). During maintenance, glucocorticoids are tapered to prednisolone 15 mg/day (maximum) at 3 months, 10 mg/day (maximum) at 6 months, and 5 mg/day (maximum) at 12–18 months.

For many types of vasculitis, long-term follow is necessary, because there is a permanent risk of relapse even many years after diagnosis and successful remission induction. Drug toxicity, especially bladder carcinoma, may become apparent only many years after the completion of cyclophosphamide therapy, and regular urine dip stick must be performed.

Relapses are classified as minor or major, according to the absence or presence of threatened vital organ function. Minor relapse is treated with an increase in prednisolone dose up to 30 mg/day, then gradual tapering and optimization of the concurrent immunosuppressive dose. Major relapse is treated with rituximab or cyclophosphamide using a similar regimen to primary remission induction, and an increase in prednisolone up to 0.5–1.0 mg/kg, maximum 1 g, intravenous methyl prednisolone or plasma exchange may be considered. Rituximab is used in preference to cyclophosphamide where the cumulative cyclophosphamide dose exceeds 15 g. In AAV, GPA is more likely to relapse than MPA. Persistence of positive ANCA is associated with an increased risk of relapse if treatment is withdrawn.

Disease refractory to induction with full-dose cyclophosphamide and prednisolone is rare. More commonly, optimal doses are not tolerated, or a prolonged relapsing disease course with high cumulative exposure to cyclophosphamide and prednisolone are the indications for alternative agents. Rituximab should be used in patients refractory to CYC. Other agents that could be considered include deoxyspergualin, and abatacept.