Abstract

Abstract Background and Aims ANCA associated vasculitis (AAV) has a peak incidence in 65 -74 yr olds. As a result, it affects an ageing population who are vulnerable to co-morbidities, polypharmacy and frailty. Due to the high burden of morbidity and mortality in these patients, it is increasingly recognised that individualised management is needed. Whilst current immunotherapies are effective, there remains caution in treating older patients due to the potential risks. Yet despite AAV being a condition that predominantly affects older people, few studies have looked specifically at the benefit of treating AAV in such age groups, or at frailty assessments tools to guide treatment. Method We aimed to evaluate treatment outcomes in older AAV patients, as well as frailty assessment tools to aid prognostication and management. A cohort study evaluating outcomes of induction immunosuppression in patients ≥75yrs was constructed from 2 centres, with subsequent meta-analysis of published data [1]. In addition, studies identifying frail patients, who may be at risk of adverse outcomes, were carried out using the quantitative tools; Hospital Frailty Risk Score (HFRS) [2] and the Clinical Frailty Scale (CFS). Primary outcomes were mortality and end stage kidney disease (ESKD). The HFRS was calculated using hospital coding data from any hospital admissions between a patient's AAV diagnosis to 2yr follow up. Patients were categorized into low, intermediate and high HFRS groups. CFS scores at presentation were documented prospectively and then repeated a minimum of 6 weeks from diagnosis. A CFS score of ≥5 was used to categorise frailty. Differences in the scores were assessed and compared to clinical outcomes. Results Retrospective analysis of our AAV cohort aged ≥75 yrs demonstrated that induction immunosuppression was associated with a significant reduction in the 2yr mortality risk [HR 0.29 (95% CI 0.09–0.93)]. Following systematic review, with a study population of 290 patients, the pooled HR by meta-analysis confirmed a significant reduction in the risk of death with induction treatment [HR 0.31 (95% CI 0.16 - 0.57)]. Treated patients had a lower rate of ESKD, but this was not statistically significant [HR 0.71 (95% CI 0.15 – 3.35)]. Looking separately at frailty assessments, mortality and ESKD were assessed according to HFRS and CFS. Thirty-four patients with AAV aged ≥75 yrs were assessed using HFRS and categorised into the low (n = 18), intermediate (n = 13) and high (n = 3) HFRS groups. All patients in the high HFRS groups had ≥1 episodes of hospitalization after diagnosis of AAV. However, there was no difference in mortality or duration of hospitalisation between the 3 categories. Forty-one patients with AAV aged ≥65yrs were assessed using the CFS. The median CFS at diagnosis and follow-up was 4. There was no significant interval change in CFS (P = 0.16) suggesting that patients did not become frailer. Instead, there was a tendency towards improved frailty scores at reassessment (n = 17, 43%), with some patients going from a CFS of 6 (moderately frail) to 3 (managing well). There was no significant difference in ESKD between those categorised as frail and non-frail (P = 1.0), although crude mortality was higher among those initially categorised as frail (P = 0.03). Conclusion Our research shows that older patients with AAV benefit from standard remission-induction therapy and those treated had favourable mortality outcomes compared to those who were not. Furthermore, frailty assessment tools do not correlate clearly with clinical outcomes. Whilst there is evidence to support the use of HFRS and CFS in a many diseases, its utility in determining frailty and potential susceptibility to adverse effects of therapy in patients with multifaceted, autoimmune inflammatory disease remains limited. Patients may present ‘frail’ as a result of significant disease burden, which has the potential to improve with appropriate treatment. We suggest that age alone and frailty at assessment should not be a limiting factor when considering treatment and prospective studies of this population are needed.

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