What is appropriate induction therapy for Granulomatosis with polyangiitis?
• High-dose oral or intravenous (IV) bolus corticosteroids are given as initial therapy, with gradual dose reduction. Corticosteroid tapering regimens may vary considerably among clinicians, and patient-specific factors also influence the rate of taper (GPA activity/response to therapy, comorbidities such as diabetes mellitus, concurrent infection, and osteoporosis). A good rule of thumb is to limit the rate of taper to roughly 10% of the current dose per week, with adjustments at the discretion of the clinician based upon the individual case.
• Cyclophosphamide was established as truly life-saving therapy in the 1970s as daily oral treatment with 2 mg/kg daily dosing regimens. However, prolonged treatment can be complicated by hemorrhagic cystitis and bladder cancer. Bolus monthly IV cyclophosphamide is safer and has similar success in disease induction as oral therapy, but relapses are more common. The “NIH lupus nephritis” regimen of 0.5 to 1.0 g/m 2 given monthly for 3 to 6 months is commonly used.
• Data suggests that rituximab is equally as effective as cyclophosphamide, with evidence of rituximab superiority in those patients presenting with relapsing disease. There is less data regarding the efficacy of rituximab monotherapy in patients with severe renal dysfunction and/or pulmonary hemorrhage requiring mechanical ventilation. One study involving patients with GPA presenting with advanced renal failure (20% of which were on hemodialysis, with a median glomerular filtration rate <30 cc/hour) demonstrated good outcomes with rituximab in combination with two doses of cyclophosphamide (compared with standard cyclophosphamide dosing regimens).
• Plasmapheresis may be considered for extremely ill patients (diffuse alveolar hemorrhage [DAH] or advanced renal failure), but recent data raises uncertainty regarding long-term benefit.
• Patients with subglottic stenosis can also be treated endoscopically via flexible bronchoscopy and the use of radial CO 2 laser incisions, dilation, and intralesional steroid injections with or without topical mitomycin C.
• In patients with limited GPA (absence of renal disease, pulmonary hemorrhage, orbital pseudotumor, vasculitic manifestations, or CNS disease), methotrexate can be considered as a steroid-sparing therapy for induction.
