Construction and Validation of a Frailty Index As a Novel Health Measure in Systemic Lupus Erythematosus

Abstract

Background/Purpose: Clinical outcomes in SLE are challenging to predict. In non-SLE populations, susceptibility to adverse outcomes has been measured using a frailty index (FI), which quantifies vulnerability via the accumulation of health deficits. Using data from the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort, we constructed and validated a frailty index for patients with SLE.

Methods: Patients fulfilling ≥4 ACR classification criteria for SLE were recruited within 15 months of diagnosis and were assessed annually for medication use, comorbidities, disease activity (SLEDAI-2K), organ damage [SLICC/ACR Damage Index (SDI)], health-related quality of life [Short-Form 36 (SF-36)] and other measures.

For our analysis, the baseline visit was defined as the first at which both SDI and SF-36 data were available. From this baseline dataset, health deficits were identified for inclusion in the SLICC frailty index (SLICC-FI). Using standard criteria, a health deficit was defined as any symptom, disease process, functional impairment, or laboratory abnormality that is: (i) acquired, (ii) associated with increasing age, (iii) associated with adverse outcomes, (iv) present in ≥1% and ≤80% of patients, and (v) missing values for <5% of patients. Once selected, the health deficits were used to calculate a baseline SLICC-FI score for each patient.

To assess validity, we estimated correlations of the SLICC-FI with existing SLE instruments, including the SDI and the SLEDAI-2K. Multivariable Cox regression was used to estimate associations between baseline SLICC-FI values and mortality risk, adjusting for relevant demographic and clinical variables.

Results: 1682 SLE patients (92.1% of the cohort) were eligible for inclusion and were predominantly female (89%) with mean (SD) age 35.7 (13.4) years and mean (SD) disease duration 18.8 (15.7) months at baseline. Of 222 candidate variables, 48 met the required criteria for inclusion as health deficits in the SLICC-FI. These included items related to organ damage, disease activity, comorbidities, and functional status. The mean (SD) baseline SLICC-FI score was 0.17 (0.08) with a range from 0 to 0.51. At baseline, SLICC-FI values were weakly correlated with both SDI (r=0.262; p<0.0001) and SLEDAI-2K (r=0.227; p<0.0001) scores. These correlations persisted after removing overlapping SDI and SLEDAI-2K items from the SLICC-FI.

Sixty-six deaths occurred during a mean (SD) follow-up of 6.7 (4.0) years. Higher baseline SLICC-FI values (per 0.05 increase) were associated with increased mortality risk (Hazard Ratio [HR] 1.59; 95% CI 1.35-1.87), after adjusting for age, sex, baseline steroid use, race/ethnicity, geographic region, and baseline SDI scores. The association between baseline SLICC-FI scores and mortality risk persisted when damage items were omitted from the SLICC-FI (HR 1.37; 95% CI 1.22-1.53) and when a subgroup of patients without baseline organ damage (SDI=0) was analyzed (HR 1.47; 95% CI 1.18-1.83).

Conclusion: The SLICC-FI is a relevant health measure in SLE. It predicts future mortality risk independent of the SDI and is a potentially valuable tool for identifying SLE patients who are most vulnerable to adverse outcomes.