Increased Risk of Severe Infections and Mortality in Patients with Newly Diagnosed Anti-neutrophil Cytoplasmic Antibody-associated Vasculitis: A Population-based Study

Background Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs) are a group of multisystem inflammatory diseases of the small blood vessels, characterized by leukocytoclastic inflammation of small blood vessels and triggered by production of ANCA autoantibodies [1]. Due to the multiorgan involvement and relapsing nature, AAV is among the systemic autoimmune rheumatic diseases with the highest morbidity and mortality [1, 2]. Objectives To evaluate the risk of severe infection and infection-related mortality among patients with newly diagnosed AAV. Methods We conducted an age- and gender- matched cohort study of all patients with incident AAV between January 1, 1997 and March 31, 2015 using administrative health data from British Columbia, Canada. Primary outcome was the first severe infection after AAV onset necessitating hospitalization or occurring during hospitalization. Secondary outcomes were total number of severe infections and infection-related mortality. Results We identified 549 AAV patients and matched them with 5,490 non-AAV individuals from the general population, yielding 184 and 509 first severe infections during 2,539 and 33,342 person-years follow-up, respectively. The crude incidence rate ratios for first severe infection and infection-related mortality were 5.03 (95% CI, 4.25-5.96) and 3.72 (95% CI, 2.44-5.67), respectively. The corresponding adjusted hazard ratios were 3.77 (95% CI 2.94-4.85) and 3.84 (95% CI, 2.13-6.91). AAV patients had an increased risk of a greater total number of severe infections with crude rate ratio of 4.99 (95% CI, 4.42-5.62) and adjusted rate ratio of 3.20 (95% CI, 2.73-3.74). Conclusion AAV is independently associated with increased risks of first severe infection (3.8-fold), a greater total number of severe infections (3.2-fold) and infection-related mortality (3.8-fold). References [1]Jennette JC, Falk RJ, Bacon PA, et al. 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum 2013;65(1):1-11. [2]Little MA, Nightingale P, Verburgh CA, et al. Early mortality in systemic vasculitis: relative contribution of adverse events and active vasculitis. Ann Rheum Dis 2010;69(6):1036-43. Table 1. Risk of severe infection in AAV relative to non-AAV during follow-up Post-AAV diagnosis first severe infection AAV cohort Non-AAV cohort N=549 N=5,490 No. of events 184 509 IR per 1,000 person-years 72.46 14.40 IRR (95% CI ) 5.03 (4.25-5.96) 1 Age and gender adjusted HR (95% CI ) 5.29 (4.43-6.31) 1 All but GC adjusted HR (95% CI ) 3.32 (2.67-4.13) 1 Fully adjusted HR* (95% CI ) 3.77 (2.94-4.85) 1 Post-AAV total number of severe infections Infection episodes 396 868 IR per 1,000 person-years 116.42 23.35 IRR (95% CI ) 4.99 (4.42-5.62) 1 Age and gender adjusted rate ratio (95% CI ) 5.27 (4.78-5.93) 1 All but GC adjusted rate ratio (95% CI ) 3.13 (2.72-3.59) 1 Fully adjusted rate ratio* (95% CI ) 3.20 (2.73-3.74) 1 Infection-related mortality No. of infection-related death events 29 85 IR per 1,000 person-years 8.53 2.29 IRR (95% CI ) 3.72 (2.44-5.67) 1 Age and gender adjusted HR (95% CI ) 4.43 (2.89-6.79) 1 All but GC adjusted HR (95% CI ) 3.67 (2.14-6.31) 1 Fully adjusted HR* (95% CI ) 3.84 (2.13-6.91) 1 Abbreviations: AAV , Antineutrophil cytoplasmic antibody-associated vasculitides; IR , incidence rate; IRR , incidence rate ratio; HR , hazard ratio; CI , confidence interval. *Adjusted for baseline covariates. All but GC HRs represent the total effect while fully adjusted HRs represent the direct effect of AAV. Disclosure of Interests None declared.