Overall, our findings demonstrate that the assessment of clinical frailty in AAV is complex and not straight forward (shown in Fig. 2). Patients may present ‘frail’ as a result of significant disease burden, which has the potential to improve with appropriate treatment. Repeated assessments of clinical frailty are seldom done in the outpatient setting and determining change in functional status and physiological reserve is challenging. In the majority of cases presented in our cohort, the CFS stayed the same or improved from initial assessment, highlighting the need for repeated measures to aid management.

Shows the multiple factors that contribute to frailty in patients presenting with AAV. The inner circle demonstrates disease contributing factors and the outer circle represents factors that contribute to frailty prior to diagnosis

AAV; Anti neutrophil cytoplasmic antibody (ANCA) associated vasculitis, CVS; cardiovascular system, VTE; venous thromboembolism

Whilst there is evidence to support the use of CFS as an assessment tool in a variety of diseases, including chronic and end stage kidney disease (12, 13), its utility in determining disease burden and frailty of patients with multifaceted, autoimmune inflammatory disease remains limited. Few studies have used CFS to assess outcomes in AAV. McGovern et al (3) applied retrospective CFS to a cohort of AAV patients and showed that age and CFS were associated with increased mortality. Furthermore, the implication of immunosuppressive treatment, in particular glucocorticoids have been related to poor outcomes, especially in the first 3 months from diagnosis (14–16). Despite this, studies such as Morris et al (17) demonstrates that older aged patients treated with immunosuppressive therapy had favourable mortality outcomes compared to those who received less aggressive treatment (17, 18). Our study further supports this given all patients that had improved CFS (n=17) were treated with immunosuppression and over three quarters received intravenous glucocorticoid treatment at presentation This suggests that despite increasing age and frailty at assessment, the perceived risks associated with immunotherapy are likely outweighed by the benefits of adequate treatment.

CFS is a useful assessment in patients aged over 65 years (10) but has potential limitations. The CFS is a brief frailty screening tool that summarises a healthcare professional’s subjective assessment of frailty status. It is possible that frailty measures that are a more objective assessment of physical frailty, such as the Frailty Phenotype (which includes walking speed and grip strength measurement) (19), are more predictive of adverse outcomes in this setting. That being said, the CFS has good diagnostic accuracy for frailty in the advanced CKD setting when using Frailty Phenotype as the reference standard (13). Regardless, we hypothesise that frailty measures will be vulnerable to the same issues, specifically the ability to differentiate frailty, the age-associated decline in multiple physiological systems (20), from AAV disease burden that is amenable to specific disease therapy.

We also recognise the limitations of this study, including the small sample size. Follow up CFS assessments were performed using different methods with no standardised interval period which may be a confounder.

In conclusion, we recommend caution when determining treatment practices based solely on frailty assessments and the CFS. Based on the current available evidence, we propose that immunosuppressive therapy should be considered even in patients who are considered frail with high CFS scores. The use of other functional assessment tools to determine the patients physiological reserve, disease burden and degree of glucocorticoid toxicity should be considered, alongside a multi-disciplinary approach involving primary care. More work is needed to fully assess the role of frailty measures in patients with AAV, so as to improve outcomes and prevent over or under treatment.