Objective To investigate the efficacy and safety of glucocorticoids combined with cyclophosphamide (CTX) and rituximab (RTX) in elderly patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis with renal involvement.

Methods Elderly patients (age ≥60 years) with ANCA-associated vasculitis and renal involvement admitted to the First Affiliated Hospital, Zhejiang University School of Medicine from December 2019 to November 2022 were retrospectively enrolled. Based on different induction treatment regimens, patients were divided into a control group (glucocorticoids + CTX) and a combination therapy group (glucocorticoids + CTX + RTX). Differences in disease remission, end stage renal disease (ESRD), mortality, relapse, and incidence of adverse events were compared between the two groups.

Results A total of 60 elderly patients with ANCA-associated vasculitis and renal involvement were ultimately included, with a median follow-up of 29.7(17.2, 38.7) months. The control group comprised 26 patients, with a median follow-up of 35.0(28.1, 40.3) months; the combination therapy group comprised 34 patients, with a median follow-up of 26.2(16.1, 35.1) months. The remission rate at 3 months (64.7% vs. 34.6%, P=0.021) and 6 months (76.5% vs. 50.0%, P=0.033)of treatment were significantly higher in the combination therapy group compared to the control group. No statistically significant differences were found between the two groups in remission rates at 12 months (85.3% vs. 65.4%, P=0.071), and last follow-up (76.5% vs. 65.4%, P=0.345), nor in the incidence of ESRD (26.5% vs. 30.8%, P=0.714), mortality (23.5% vs. 26.9%, P=0.764), and relapse (14.7% vs. 23.1%, P=0.507) during follow-up.Regarding medication dosage, the cumulative RTX dose in the combination therapy group at 6 months and last follow-up was 0.6(0.4, 1.2)g and 0.8(0.5, 1.2)g, respectively. The maintenance dose of glucocorticoids (calculated as prednisone dose)at 6 months: (2.4±1.1)g vs. (4.3±0.8)g, P < 0.001; at last follow-up: 3.5(2.1, 4.3)g vs. 6.5(5.0, 7.7)g, P < 0.001, cumulative glucocorticoid dose (methylprednisolone pulse therapy dose converted to equivalent prednisone dose) at 6 months: (3.7±1.4)g vs. (5.3±0.9)g, P < 0.001; at last follow-up: 4.1(3.2, 6.2)g vs. 7.1(6.2, 8.9)g, P < 0.001, and cumulative CTX dose at 6 months: 3.3(1.1, 6.2)g vs. 5.2(4.5, 6.0)g, P < 0.001; at last follow-up: 3.6(0.9, 6.2)g vs. 6.0(5.5, 6.8)g, P=0.001 were significantly lower in the combination therapy group than in the control group. Furthermore, the proportion of patients successfully tapering prednisone to ≤15 mg/day by week 8 of treatment (76.5% vs. 19.2%, P < 0.001) and the proportion completely discontinuing prednisone by 6 months of treatment (44.1% vs. 3.8%, P < 0.001) were significantly higher in the combination therapy group. In terms of safety, the incidence of new-onset hyperlipidemia at 6 months (14.7% vs. 42.3%, P=0.017) and last follow-up (29.4% vs. 73.1%, P=0.013), and the incidence of new-onset hyperglycemia at last follow-up (17.6% vs. 50.0%, P=0.008) were significantly lower in the combination therapy group. No significant differences were observed in the incidence of severe infections, malignancies, or cardiovascular and cerebrovascular events between the two groups (all P > 0.05).

Conclusions For elderly patients with ANCA-associated vasculitis and renal involvement, the regimen of glucocorticoids combined with CTX and individualized RTX demonstrates potential advantages in early remission rate, glucocorticoid tapering, and control of cumulative CTX dose, without increasing the risk of serious adverse events. This regimen may represent an alternative treatment option for this patient population; however, its long-term efficacy and safety require further validation through prospective randomized controlled trials.