Antineutrophil cytoplasmic antibody associated vasculitides with renal involvement: Open challenges in the remission induction therapy

Table 1 Randomized controlled trials for induction of remission in antineutrophil cytoplasmic antibody associated vasculitides with renal involvement and cyclophosphamide-sparing regimens

Name of the Trial (number of patients)	Inclusion criteria	Treatment groups (drug dose)	Primary end points	Outcome
CYCLOPS[7] (149)	New diagnosis of GPA, MPA, or relapse with renal involvement, creatinine 150–500 μmol/L (1.7- 5.66 mg/dL)	Intravenous pulse CYC (15 mg/kg) vs Daily oral CYC (2 mg/kg)	Remission, Time to relapse	Pulse CYC not inferior to oral CYC Less leucopenia and trend towards more relapses with pulse CYC
CORTAGE[8] (104)	New diagnosis of MPA, GPA, EGPA, PAN and age > 65 yr	Rapid CCS tapering and reduced-dose intravenous pulse CYC (500 mg) vs Standard intravenous pulse CYC (500 mg/m²)	Severe adverse events	Less severe adverse events with reduced immunosuppression, no difference in remission and relapse rates
RAVE[10] (197)	New or relapsing GPA or MPA creatinine ≤ 353.6 μmol/L (4 mg/dL)	RTX (4 × 375 mg/m² infusions) vs Daily oral CYC	Complete remission and cessation of CCS at 6 mo	RTX not inferior to oral CYC, RTX better in patients with relapse than after first diagnosis
RITUXVAS[11] (44)	New diagnosis of AAV and severe renal involvement	RTX (4 × 375 mg/m² infusions) plus two intravenous pulses of CYC vs intravenous pulse CYC only	Sustained remission	RTX not inferior to pulse CYC

AAV: Antineutrophil cytoplasmic antibody associated vasculitides; CYC: Cyclophosphamide; RTX: Rituximab; CCS: Corticosteroids; GPA: Granulomatosis with polyangiitis; MPA: Microscopic polyangiitis; EGPA: Eosinophilic granulomatosis with polyangiitis; PAN: Polyarteritis nodosa.