Treatment of ANCA vasculitis
What are the medical therapies for the treatment of ANCA vasculitis?
Treatment of the ANCA vasculitis centers on the use of immunosuppressive therapies. Initial therapy, or induction, for organ-threatening or life-threatening disease involves the use of corticosteroids in combination with either cyclophosphamide (a cytotoxic agent) or rituximab (a B-cell–depleting agent). Compared to a regimen of daily oral cyclophosphamide, pulse intravenous cyclophosphamide is associated with a similar rate of remission. Although it is associated with a higher rate of relapse, the long-term patient and kidney survival are not significantly different between these two approaches. The pulse intravenous cyclophosphamide regimen results in a significantly lower cumulative dose, which is desired, as the long-term risk of cancer is commensurate with the life-long cumulative exposure to this drug. In a landmark randomized, controlled, clinical trial, induction therapy with a combination of corticosteroids plus rituximab was not inferior to corticosteroids plus oral cyclophosphamide followed by azathioprine in patients with mild or moderately severe disease. However, data on the use of rituximab in lieu of cyclophosphamide in patients with severe pulmonary hemorrhage or severe kidney failure are relatively scant. In patients with relapsing ANCA vasculitis, the use of rituximab was associated with a greater rate of remission, and avoids repeated exposure to cyclophosphamide.
For patients with non-organ- or non-life-threatening disease and well-preserved kidney function, glucocorticoids in combination with methotrexate or mycophenolate mofetil have been studied for induction therapy. Relapse rates may be higher with these agents, and they should not be used in the setting of kidney dysfunction or pulmonary hemorrhage. The use of these agents is currently supplanted by that of rituximab for induction therapy.
Following induction of remission after 3 to 6 months initial therapy, rituximab or azathioprine can be used as maintenance therapy. In a trial of maintenance therapy, the use of rituximab 500 mg every 6 months was associated with a lower relapse rate than with azathioprine. Mycophenolate mofetil or methotrexate (in patients with good kidney function) can also be considered for use as maintenance therapy in patients who are intolerant to rituximab or azathioprine. No data is currently available to guide the duration of maintenance therapy. Generally, maintenance therapy is suggested for 18 to 24 months after a remission is attained.
Relapses of disease should be treated as new disease presentation, with corticosteroids combined with cyclophosphamide or rituximab in the setting of severe disease. For those patients who initially received cyclophosphamide therapy, the use of rituximab for relapse is favored to minimize lifetime cumulative cyclophosphamide dose. Upon remission after relapse, the prior maintenance therapy should be modified or intensified.
Disease that is refractory to corticosteroids and cyclophosphamide or rituximab may benefit from the addition of the other agent (i.e., adding rituximab to patients who have received cyclophosphamide, and vice versa), plamapheresis, or intravenous immunoglobulin. However, data for the use of these measures in this fashion have been primarily in the form of case reports or case series.
