Progression and clinical implications of frailty in patients with systemic sclerosis

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

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.

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).

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.