Progression and clinical implications of frailty in patients with systemic sclerosis

Introduction/objectives: To identify the frequency, correlates and progression of frailty in systemic sclerosis (SSc).

Method: All Australian Scleroderma Cohort Study participants meeting ACR/EULAR criteria with a calculable FRAIL Scale score were included. FRAIL Scale scores were calculated annually and were used to group participants as 'robust', 'pre-frail' or 'frail'. Progression of frailty over time was examined by comparing first-recorded, highest-recorded and last-recorded FRAIL Scale scores for each participant. Determinants of frailty at each visit were evaluated with ordinal logistic regression. Survival was analysed using Cox hazard modelling.

Results: Of 1703 participants, 14% and 53% met criteria for frailty or pre-frailty respectively, with 33% consistently robust. Among initially frail participants, 40% remained frail and 60% improved to pre-frailty/robustness. Of pre-frail participants, 15% became frail while 32% improved to robustness. One-third of initially robust participants progressed to pre-frailty/frailty. SSc-specific determinants of frailty included diffuse SSc (odds ratio (OR) 1.4, 95% confidence interval (CI) 1.1-1.8, p < 0.01), pulmonary arterial hypertension (OR 7.1, 95% CI 5.1-9.9, p < 0.01), interstitial lung disease (OR 1.6, 95% CI 1.3-2.0, p < 0.01), proximal weakness (OR 1.5, 95% CI 1.2-2.0, p < 0.01) and lower-tract gastrointestinal symptoms (OR 1.5, 95% CI 1.3-1.8, p < 0.01). Older age (OR 1.1, 95% CI 1.1-1.2, p < 0.01), raised CRP (OR 1.7, 95% CI 1.4-2.0, p < 0.01) and anaemia (OR 1.4, 95% CI 1.2-1.7, p < 0.01) were also significantly associated with frailty. A graded risk of death was observed with the diagnosis of pre-frailty and frailty states (hazard ratio (HR) 3.5, 95% CI 2.6-4.8, p < 0.01; and HR 9.8, 95% CI 6.8-14.1, p < 0.01 respectively). Frailty and pre-frailty were associated with reduced health-related quality-of-life and physical function (p < 0.05).

Conclusions: Frailty and pre-frailty are common in SSc and contribute to morbidity and mortality. Both SSc and non-SSc determinants of frailty exist. Frailty in SSc is a dynamic phenomenon with potential to deteriorate or improve over time.