Frailty Predicts Damage in SLE: Patients considered frail at baseline had twice the rate of lupus damage
A frailty index helped predict future disease damage in patients with systemic lupus erythematosus (SLE), an international group of researchers and experts reported.
On a multivariable analysis, each 0.05-point increase in the baseline frailty index developed by the Systemic Lupus International Collaborating Clinics (SLICC) group was associated with a 20% higher rate of later damage accumulation (95% CI 14%-27%), according to John G. Hanly, MD, of Dalhousie University in Halifax, Nova Scotia, and colleagues. That calculation was made after adjustment for baseline age, sex, ethnicity, education, SLE Disease Activity Index (SLEDAI), and use of corticosteroids, antimalarials, and immunosuppressives, the investigators reported online in Arthritis & Rheumatology.
"In geriatric medicine and other disciplines, susceptibility to adverse outcomes is quantified using the construct of frailty, defined as increased vulnerability due to diminished ability to respond to physiologic stressors," the team explained.
The SLICC investigators recently developed a frailty index specific to SLE, and found that it was predictive of mortality. To further explore the utility of this tool, Hanley and co-authors calculated an individual score for 1,549 patients enrolled in their multinational inception cohort and analyzed the relationship with organ damage measured on the SLICC/American College of Rheumatology Damage Index (SDI). Increasing damage in SLE has been linked with mortality, greater healthcare costs, and worse health-related quality of life.
The index includes 48 specific health deficits, including symptoms, functional impairments, and laboratory abnormalities, with each item scored as zero (complete absence) or one (fully present). The final score was calculated as the sum of individual deficit scores divided by the total number of deficits. For example, a patient with a sum of 12 deficits out of a possible 48 would have a frailty index of 0.25. Baseline frailty scores ranged from 0.004 to 0.510, with a median of 0.16. A total of 27.2% of patients were considered frail at baseline, in that their index was higher than 0.21, and 23.9% had organ damage at baseline, with SDI scores higher than zero. During a mean follow-up of 7.2 years, 21.4% of patients had a one-point increase on the SDI, 11.5% had a 2-point increase, and 9.2% had an increase of three or more points. The remaining 57.8% had no increase.
Patients who were considered frail at baseline had twice the rate of increase in SDI per patient-year compared with those classified as non-frail, with an incidence rate ratio of 1.98 (95% CI 1.68-2.34). Those with damage present at baseline also had higher rates of increase in SDI compared with those without damage at baseline (IRR 1.70, 95% CI 1.43-2.01). In an unadjusted model, each additional 0.05 points on the baseline frailty index was associated with a 26% higher rate of change on the SDI (IRR 1.26, 95% CI 1.20-1.33), while each one-point increase in baseline SDI was associated with an increase of 31% in the rate of later damage accrual (IRR 1.31, 95% CI 1.20-1.43). Other factors that were associated with increasing damage in the univariate analysis included male sex, older age, higher scores on the SLEDAI, and use of corticosteroids or immunosuppressives. Protective factors included use of antimalarial drugs and post-secondary educational achievement. In a multivariable model that included both the baseline frailty index and SDI as independent variables, both factors had statistically significant associations with the rate of SDI increase per patient-year:
- SLICC frailty index (per 0.05 increase): IRR 1.19, 95% CI 1.13-1.25 (P<0.001)
- SDI (per one-point change): IRR 1.10, 95% CI 1.01-1.21 (P=0.038)
Moreover, the multivariable model that included both baseline frailty index and SDI score more accurately predicted damage accumulation, with a likelihood ratio test statistic of 40.49 (P<0.001).
"Importantly, this study focused on predictors of damage accrual based on information available to clinicians early in the course of incident SLE," Hanly and colleagues wrote.
However, the overall impact of increasing frailty over time remains to be examined, and whether there are varying influences on different types of organ damage is not known.
"The SLICC frailty index holds potential value as a prognostic tool for identifying SLE patients who are at increased risk for the development of significant organ damage. As frailty is potentially reversible, the SLICC frailty index may also be useful as an outcome measure in future intervention studies," the researchers concluded.
A limitation of the study, they said, was the different duration of follow-up among patients.
The authors reported support from the Canadian Institutes of Health Research; Lupus UK; the National Health Services Trust; the National Institute for Health Research/Wellcome Trust; the National Institutes of Health; the Singer Family Fund for Lupus Research; the Arthritis Society; Arthritis Research UK; the Danish Rheumatism Association; the Novo Nordisk Foundation; and the Department of Education, Universities and Research of the Basque Government.