Background/Purpose: Despite therapeutic advances in ANCA-associated vasculitis (AAV), patients continue to be exposed to considerable treatment morbidity from long-term glucocorticoid (GC) use.  The optimal duration of GC treatment has not been studied in AAV.  We conducted an open-label, proof of concept study investigating whether an 8-week GC taper, in combination with rituximab (RTX), would be sufficient to control AAV in a subset of patients who have a more favorable prognosis.  Such an approach would reduce the cumulative GC dose by at least 45%, thereby diminishing the potential for GC toxicity.     

Methods: Patients with granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) who had newly diagnosed or relapsing disease with a BVAS/WG of 3 or more were eligible to participate.  Patients with diffuse alveolar hemorrhage requiring intubation, MPO-ANCA-positive patients with severe renal involvement (GFR < 30 ml/min/1.73m²) and PR3-ANCA-positive patients with glomerulonephritis were excluded.  Subjects were treated with RTX 375mg/m² weekly for four weeks and an 8 week GC taper (60mg x 2 weeks, 40mg x 2 weeks, 30mg x 1 week, 20mg x 1 week, 10mg x 1 week and 5mg x 1 week then off). Patients on chronic GCs prior to trial entry were permitted to taper to their pre-relapse dose.  The primary outcome was no disease activity (BVAS/WG = 0) and being off prednisone (or at baseline dose for those on chronic GCs prior to trial entry) at 6 months.

Results: Eighteen patients have enrolled and 14 have completed the study to date (Table 1).  The mean age was 59.7 and 66% were female.  Sixty-seven percent had GPA, 39% were PR3-ANCA-positive and 44% had relapsing disease.  Mean BVAS/WG at study entry was 5.6.  Nine of fourteen patients (64%) successfully reached the primary endpoint.  Of the 5 patients who failed the primary endpoint, 2 had flares of glomerulonephritis, one had relapse of diffuse alveolar hemorrhage, one of mononeuritis multiplex and one had recurrent meningitis.  All of these patients reached remission after treatment according to best medical judgment.  There were no relapses of clinical features associated with granulomatous inflammation.  Vasculitis damage index at study entry was 0.9 and 1.5 at the completion of the study.

Conclusion : A 2-month course of prednisone in combination with rituximab resulted in 64% of patients reaching and maintaining complete remission at 6 months, similar to rates reported in the Rituximab in ANCA-associated Vasculitis (RAVE) trial.  Relapses were primarily due to manifestations associated with vasculitis rather than granulomatous inflammation.  Further study of this protocol in larger numbers of patients should be considered.

Table – Demographic characteristics and organ involvement at baseline