Adverse events and infectious burden, microbes and temporal outline from immunosuppressive therapy in antineutrophil cytoplasmic antibody-associated vasculitis with native renal function

Abstract

Background: Disease control in anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV) with immunosuppression is effective but burdened by adverse events, especially infections. The study goal was to evaluate risks and types of infections in patients with AAV.

Methods: Biopsy-proven AAV patients (diagnosed 1/1991-6/2011) followed in an inception cohort were evaluated for adverse events. Severe infections (requiring intravenous antibiotics, intensive care unit, or causing death) were recorded. Infection number was grouped as none, 1-2 or ≥3. Cox regression was used to estimate hazard ratios with 95% confidence intervals.

Results: A total of 489 patients (median age 59; 47% female, 55% myeloperoxidase-ANCA) were followed for 2.8 years (median). At 1, 2 and 5 years cumulative incidence of infection was 51, 58 and 65% and severe infection was 22, 23 and 26%. Pulmonary and upper respiratory infections were most common (42 and 30% ever experienced each, respectively), highest in the first 3 months. Staphylococcus aureus was most frequently seen among positive cultures (41%, 78 S. aureus/192 total positive cultures), and only one Pneumocystis jiroveci pneumonia (6 weeks into treatment). All-cause death in 12 months was associated with infections (% deaths: 0 infections 3%; 1-2 infections 10%, ≥3 infections 13%, P = 0.002). Controlling for age, sex and kidney function, patients with severe infections were 4.2 times more likely to die within 12 months (95% CI 2.0-8.7; P = 0.001).

Conclusions: More infections increase the risk of a severe infection which increases risk of all-cause mortality. Respiratory and S. aureus infections are dominant. Targeted prophylactic therapy could decrease morbidity.

Keywords: ANCA; glomerulonephritis; immunosuppression; outcomes; risk factors.

© The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Figures

FIGURE 1:

Depiction of studied patient population.

FIGURE 2:

Unadjusted cumulative incidences of events in the entire cohort.

FIGURE 3:

Number of infections experienced within 3 month time intervals from initiation of first therapy out to 24 months by (a) infection type and by (b) microbiologic culture type (among 128 patients cultured with 112 having 192 positive cultures). Multiple infections and cultures per person are shown.