Cyclophosphamide vs rituximab induction therapy for ANCA-associated vasculitis. A systematic review and meta-analysis of 12-month mortality.

BACKGROUND: ANCA-associated vasculitis (AAV) survival rates have improved with advancement in therapeutics. The impact on mortality in AAV stratified by induction therapy is not known. AIM: To compare 12-month mortality in individuals with AAV who received cyclophosphamide versus rituximab induction therapy. METHODS: A systematic literature review was undertaken to identify studies assessing 12-month mortality after cyclophosphamide or rituximab for AAV induction therapy. A meta-analysis was conducted to estimate pooled results using a random effects model. The homogeneity of the study results was assessed using the I2 statistic and sensitivity analysis was undertaken to assess the impacts of study populations and study design on any statistical heterogeneity. RESULTS: 48 studies were included in the analysis. The overall mortality at 12 months for cyclophosphamide was 10.7% (95% CI 8.4-13.2) and rituximab was 5.9% (95% CI 3.2-9.4). The difference in 12-month mortality between induction therapies was 4.8% (95% CI 0.5-9.0; p < 0.001) favouring rituximab. Analysis from 5 studies that directly compared these treatments showed a small non-statistically significant reduction in mortality for cyclophosphamide (difference=1.34%, 95% CI -6.5-3.7; p = 0.59). Subgroup sensitivity analysis conducted based on year of treatment, sex and age, showed a reduced but not statistically significant mortality in the rituximab group. CONCLUSION: Overall, there was a statistically significant difference favouring rituximab in 12-month mortality rates after cyclophosphamide or rituximab induction treatment for AAV. Subgroup sensitivity analysis considering study populations consistently supported this result although only treatment for GPA and baseline BVAS <17 reached statistical significance. Further direct studies between cyclophosphamide and rituximab induction are required.