Rituximab therapy compared to cyclophosphamide in ANCA-associated vasculitis

The antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are a rare group of autoimmune inflammatory conditions affecting small to medium blood vessels. Although rituximab is an established treatment for AAV, its effectiveness in patients with the most severe kidney involvement remains uncertain. The RAVE (Rituximab versus Cyclophosphamide for ANCA-Associated Vasculitis) trial excluded patients with creatinine >354 µmol/L, while the RITUXIVAS (Rituximab versus Cyclophosphamide in ANCA-Associated Renal Vasculitis) trial combined rituximab with two cyclophosphamide pulses, making it difficult to assess the effectiveness of rituximab alone in this population. Consequently, evidence for rituximab alone in severe renal AAV is therefore limited.  

This retrospective cohort study from two Birmingham renal units aimed to address this evidence gap by comparing outcomes in patients with severe renal AAV treated with rituximab or cyclophosphamide as induction therapy. It included 107 consecutive patients (2010–2023) with peak creatinine >354 µmol/L. Of these, 66 received pulsed cyclophosphamide and 41 received rituximab, both with high-dose steroids. The groups had broadly similar disease severity at presentation including dialysis requirement (56% vs 71%), peak creatinine (511 vs 538 µmol/L) and eGFR (9 vs 7 mL/min/1.73 m²).  

The primary outcome was sustained remission with independent renal function at 12 months, achieved in similar proportions of patients receiving cyclophosphamide and rituximab (52% vs 49% ; p=0.78). At 12 months, independent renal function (65% vs 56%) and eGFR (28 vs 31) did not differ significantly. Survival was numerically lower with rituximab (83% vs 94%; p=0.068). Plasma exchange was used considerably more often in the cyclophosphamide group (39/66 vs 7/41), potentially complicating comparisons between treatment groups. 

Although limited by its small sample size, retrospective design and possible treatment selection bias, this study adds evidence from a population largely excluded from previous trials. Its findings suggest that rituximab with steroids may be a reasonable alternative to cyclophosphamide for induction therapy in severe renal AAV, although larger prospective studies are needed to establish comparative effectiveness. 

The full article can be read here.