Long-term risk of malignancies in ANCA-associated vasculitis

OBJECTIVES: Patients with anti-neutrophil cytoplasmic antibodies-associated vasculitis (AAV) have an increased malignancy risk, largely attributed to immunosuppressive therapy. Given the latency period for malignancy development, data on long-term incidence in large AAV cohorts remain limited. This study aimed to assess the cumulative malignancy incidence in patients with AAV from European Vasculitis Society (EUVAS) clinical trials (1995-2012).

METHODS: We analysed 848 patients with AAV from 17 European countries. Data were collected via questionnaires sent to the principal investigators of 7 EUVAS trials. Standardised incidence ratios (SIRs) were calculated using national malignancy databases.

RESULTS: At a median follow-up of 8 years (IQR: 2.2-8.8 years), 135 patients experienced 153 malignancies. The overall SIR was 1.40 (95% CI: 1.18-1.64), primarily driven by nonmelanoma skin cancer (NMSC; SIR: 3.52; 95% CI: 2.6-4.7). Excluding NMSC, the SIR was 1.17 (0.96-1.4). The most common malignancies were NMSC (62 cases), prostate (11.1%), and lung (9.8%). The incidence of first malignancy was 2.01 per 100 person-years (95% CI: 1.70-2.39). Cumulative malignancy incidence was 10.8% at 5 years, 19% at 10 years, and 38.2% at 20 years. Patients diagnosed before the age of 40 years had a 30-fold increased risk of NMSC (SIR: 30; 95% CI: 6.03-87.65). Cyclophosphamide use for >6 months, azathioprine duration, and age >65 years were independent risk factors. The diagnosis of malignancy predicted worse survival (log-rank = 9.2; = .002).

CONCLUSIONS: Patients with AAV have a significantly increased risk of NMSC, particularly younger individuals, while solid tumour risk is not significantly elevated. Prolonged cyclophosphamide and azathioprine use were associated with malignancy development.