Risk factors for poor prognosis in ANCA-associated vasculitis with interstitial lung disease: a systematic review and meta-analysis

OBJECTIVE: Antineutrophil cytoplasm antibody-associated vasculitis (AAV) with interstitial lung disease (AAV-ILD) is the main manifestation of AAV involving the lung, further increasing the risk of poor prognosis in patients with AAV. This study aimed to investigate the risk factors associated with mortality in patients with AAV-ILD. METHODS: In Web of Science, PubMed, Embase and Scopus databases, a comprehensive search was performed for English studies on AAV and ILD published from inception date until May 17, 2024. Hazard ratios (HR) and 95% confidence intervals (CI) of mortality-related risk factors in AAV-ILD were collected, and subgroup analyses were carried out based on different candidate risk factors. Cochran's Q statistic and inconsistency value were utilized to assess the heterogeneity of included studies. Sensitivity analysis was executed using one-by-one elimination method, and publication bias was evaluated with Egger's test and the trim-and-fill method. RESULTS: A total of 654 patients with AAV-ILD in eight studies were included for the pooled analysis of mortality risk factors. The results showed that age (HR = 1.06, 95%CI: 1.04, 1.08), ever smoker (HR = 1.61, 95%CI: 1.13, 2.29), usual interstitial pneumonia pattern (HR = 2.07, 95%CI: 1.43, 3.00), acute exacerbation (HR = 2.73, 95%CI: 1.70, 4.40) and microscopic polyangiitis (HR = 4.03, 95%CI: 1.70, 9.55) were associated with an increased risk of AAV-ILD mortality. Conversely, percent predicted forced vital capacity (HR = 0.97, 95%CI: 0.96, 0.99) and immunosuppressant for induction (HR = 0.40, 95%CI: 0.28, 0.58) were associated with a reduced risk of AAV-ILD mortality. Male (HR = 1.27, 95%CI: 0.90, 1.80), nervous system involvement (HR = 0.99, 95%CI: 0.65, 1.52), renal involvement (HR = 1.24, 95%CI: 0.97, 1.95) and five factor score ≥ 1 (HR = 1.00, 95%CI: 0.67, 1.48) showed no significant correlation with mortality risk in patients with AAV-ILD. Heterogeneity test indicated no significant heterogeneity among the pooled studies. The results of sensitivity analysis, Egger's test and the trim-and-fill method revealed that the pooled findings were stable and reliable. CONCLUSION: The pooled analyses demonstrated that age, ever smoker, usual interstitial pneumonia pattern, acute exacerbation and microscopic polyangiitis were risk factors for mortality in patients with AAV-ILD, while percent predicted forced vital capacity and immunosuppressant therapy for induction serve as protective factors against mortality. A systematic understanding of the risk factors for AAV-ILD may provide clues for developing effective interventions and managements to improve poor prognosis in patients. Key Points • Increase of age, ever smoker, usual interstitial pneumonia pattern, acute exacerbation and microscopic polyangiitis were risk factors for poor prognosis in patients with AAV-ILD. • High level of percent predicted forced vital capacity and immunosuppressant therapy for induction serve as protective factors against poor prognosis. • Male, nervous system involvement, renal involvement and five factor score ≥ 1 showed no significant correlation with poor prognosis in patients with AAV-ILD.