Pos1160 age, frailty, and outcomes in older adults with anca-associated vasculitis

Background Older adults with ANCA-associated vasculitis (AAV) have differences in clinical presentation, as well as increased mortality and risk of infections, when compared to younger adults. Despite a high incidence of AAV in older adults, these individuals are underrepresented in clinical trials. Frailty, a geriatric syndrome associated with increased morbidity and mortality, has not been adequately studied in older adults with AAV. Better characterization of outcomes and risk factors in these patients is needed to inform treatment. Objectives To compare the risks of and factors associated with early (within 2 years) end-stage renal disease (ESRD), severe infection, and death in adults with a new diagnosis of AAV who are ≥ 75 years old vs 65-74 years old. Methods Patients ≥ 65 years were included from the 2002-2019 Mass General Brigham AAV cohort, a consecutive inception cohort. EGPA patients were excluded. Covariates including demographics, disease characteristics, and comorbidities (Charlson comorbidity index) were assessed at baseline. Disease activity at time of diagnosis was assessed using the Birmingham Vasculitis Activity Score (BVAS/WG). Frailty was measured at baseline using a claims frailty index, and pre-established cut-offs were utilized to define degrees of frailty (robust, pre-frail, mildly frail, and moderately/severely frail). [1] Death and ESRD were ascertained from linkage to national registries and/or medical records. Severe infections were identified utilizing inpatient data and/or death certificates. The cumulative incidence of death, ESRD and severe infections within 2 years were estimated. In univariate analyses, we assessed factors associated with outcomes within 2 years. Results 298 individuals were included. Most patients were female (61%), white (86%), MPO-ANCA+ (80%), and had renal involvement (72%). Patients ≥ 75 years old (n=156) had a median age of 81 years, while median age was 69 years in the 65-74 years group. The cumulative incidence at 2 years of the composite outcome of ESRD/death (23.1% [95% CI 16.5, 29.7]) vs 5.6% [95% CI 1.8, 9.4]) and severe infection (34.0% [95% CI 26.5, 41.4] vs 12% [95% CI 6.6, 17.3]) higher in AAV patients ≥ 75 vs 65-74 years old. Age ≥ 75 years was associated with an increased risk of ESRD/death (hazard ratio (HR) 4.42, 95% CI 2.05-9.51); frailty was not (HR 2.71, 95% CI 0.63,11.72) (Table 1). In contrast, frailty (HR 19.39, 95% CI 2.77,135.66) as well as age ≥ 75 years (HR 3.21, 95 CI% 1.87, 5.52), pulmonary involvement (HR 1.98, 95% CI 1.23, 3.18), and higher baseline comorbidity burden (HR 1.13, 95% CI 1.06, 1.20) were associated with severe infection risk. Conclusion Compared to AAV patients aged 65-74 years, AAV patients ≥ 75 years had a higher incidence of death/ESRD and severe infections. Older age but not baseline frailty was associated with ESRD/mortality risk whereas frailty was a very strong risk factor for severe infection. These findings highlight the need for innovative considerations beyond age when assessing outcome risks in AAV. Reference [1]Kim DH, et al. J Gerontol A Biol Sci Med Sci. 2019;74(8):1271-1276 Table 1. Univariate analyses of factors associated with composite outcome and severe infections within 2 years Factors Composite outcome (ESRD/Death) Severe infection HR (95% CI) HR (95% CI) Age ≥ 75 years (Ref, 65-74 years) 4.42 (2.05, 9.51) 3.21 (1.87, 5.52) Female sex (Ref, male) 0.75 (0.41, 1.35) 0.70 (0.44, 1.12) Comorbidities (CCI per 1 unit) 1.07 (0.97, 1.19) 1.13 (1.06, 1.20) Frailty Robust Pre-frail Frail REF 1.85 (0.44, 7.80) 2.71 (0.63, 11.72) REF 4.01 (0.56, 28.72) 19.39 (2.77, 135.66) BVAS (per 1 unit) 1.14 (0.99, 1.31) 1.05 (0.94, 1.18) Organ involvement Renal (Ref, none) Pulmonary (Ref, none) 1.58 (0.76, 3.29) 1.75 (0.95, 3.20) 1.26 (0.74, 2.16) 1.98 (1.23, 3.18) Induction Regimen (CYC-based vs not) 1.45 (0.72, 2.94) 1.07 (0.64, 1.78) ESRD = end-stage renal disease, HR = hazard ratio, CI = confidence interval, CCI = Charlson Comorbidity Index, BVAS = Birmingham Vasculitis Activity Score, CYC = cyclophosphamide Figure 1. Composite outcome (A) and severe infections (B) by frailty status at baseline. Acknowledgements: NIL. Disclosure of Interests Sebastian E. Sattui Consultant of: Sanofi (unpaid)., Grant/research support from: Dr. Sattui is supported by a Rheumatology Research Foundation RISE Pilot Award and the Bristol Myers Squibb Foundation Winn Career Development Award. Dr. Sattui has received research funding from AstraZeneca., Xiaoqing Fu: None declared, Claire Cook: None declared, Shruthi Srivatsan: None declared, Yuqing Zhang: None declared, Zachary Wallace Consultant of: Dr. Wallace reports consulting fees from Viela Bio, Horizon, Zenas Biopharma, and MedPace, and serves on advisory boards for Horizon, Shinogi, and Visterra/Otsuka., Grant/research support from: Dr. Wallace ZSW is funded by NIH/NIAMS [K23AR073334 and R03AR078938] and the Rheumatology Research Foundation [K Supplement]. Dr. Wallace reports research support from Bristol-Myers Squibb and Principia/Sanofi.