Kidney Outcomes After Combining Rituximab with Cyclophosphamide Compared with Rituximab Alone: Strategy in ANCA-Associated Vasculitis with Rapidly Progressive Glomerulonephritis

Background: The efficacy of combining rituximab (RTX) with cyclophosphamide (CYC) vs. rituximab (RTX) alone strategy in ANCA-associated vasculitis (AAV) with rapidly progressive glomerulonephritis (RPGN) is unknown. Methods: We conducted a multi-center retrospective study of patients with AAV with RPGN who were treated with RTX+CYC vs. RTX alone in combination with steroids for induction treatment in 2017-2021. Use of plasma exchange (PLEX) was not an exclusion criterion. Patients who used other concomitant immunosuppressive agents were excluded. Primary outcomes were improvement in eGFR and risk of relapse at 1, 2, and 5 years. Other outcomes included adverse events, including death and severe infections. Results: A total of 28 and 42 patients were included in the RTX and RTX+CYC groups, respectively. Baseline characteristics are summarized in Table 1. At presentation, the RTX+CYC group had lower nadir eGFR and % normal glomeruli and a higher rate of kidney replacement therapy (KRT) requirement (Table 1). Median eGFR improved by 17 (IQR 8-27) mL/min/1.73 m2 in the RTX group and 15 (IQR 8-26) in the RTX+CYC group at 1 year (p=0.49) (Fig.1) and remained stable at 2 years. Among patients who needed KRT, 75% (3/4) vs. 73% (8/11) became KRT-independent in RTX vs. RTX+CYC groups, respectively. During follow-up, 25% (7/28) in the RTX group had at least one relapse, while none relapsed in RTX+CYC group. Severe infections and death occurred in 46% (13/28) vs. 41% (17/42) and 14% (4/28) vs. 12% (5/42) in RTX vs. RTX+CYC groups, respectively. Conclusion: In AAV with severe RPGN, treatment with RTX+CYC vs. RTX alone led to a similar renal recovery, despite RTX+CYC group having more severe renal disease at presentation. Combining RTX+CYC might reduce the risk of AAV relapse. Larger and randomized studies are needed.