Lupus Frailty Index Predicts Organ Damage

Patients with longstanding systemic lupus erythematosus (SLE) who were considered frail were more likely to accrue disease damage over time, a secondary analysis of data from a Chicago lupus cohort found.

On a multivariate analysis that controlled for age, race, and duration of disease, a 0.05-point increase on the baseline frailty scale was associated with a 28% greater likelihood of disease damage at 5 years (OR 1.28, 95% CI 1.01-1.63), reported Rosalind Ramsey-Goldman, MD, DrPH, of Northwestern University Feinberg School of Medicine in Chicago, and colleagues.

And while most frail patients remained stable over time, almost one-third had a decrease at 5 years. "Importantly, frailty is reversible," the researchers wrote in their study online in Arthritis Care & Research.

Frailty is defined as a clinical phenotype characterized by weight loss, sedentary lifestyle, exhaustion, slow gait, and lack of hand grip strength. "The etiology of frailty is complex and includes chronic inflammation and immune activation as evidenced by elevated levels of interleukin-6, tumor necrosis factor-α, and C-reactive protein," the team explained.

A lupus-specific frailty index was developed by the Systemic Lupus International Collaborating Clinics (SLICC) group; the index includes multiple health deficits associated with disease activity, organ damage, and quality of life, and has been shown to be predictive of adverse outcomes in the SLICC inception cohort.

The SLICC/American College of Rheumatology Damage Index (SDI) is a widely used tool for evaluation of organ damage in SLE, also reflecting health and mortality risk. The prevention of irreversible damage is a major goal of lupus management, but it has been challenging to predict which SLE patients are at risk for organ damage. The SLICC Frailty Index accurately predicted poor outcomes in the patients in the inception cohort, whose mean age at baseline was 35.7 years and whose disease duration averaged only 14 months, but the utility in longstanding disease had not been determined.

Ramsey-Goldman and colleagues therefore decided to analyze data from the longitudinal epidemiologic Study of Lupus Vascular and Bone Long-Term Endpoints (SOLVABLE), including 149 patients enrolled from 2004 to 2013 who had baseline and 5-year follow-up visits.

In the analysis, the SLICC Frailty Index included 46 health deficits, each being scored from 0 (no deficit) to 1 (full deficit). Patients were categorized as being frail if they had a Frailty Index above 0.21; as least fit, with an index of 0.10 to 0.21; or relatively fit, with an index of 0.10 or lower. A change greater than 0.03 at 5 years was considered clinically significant.

Damage accrual was defined as any rise in the SDI at 5 years.

All participants in the study were women; mean age was 43.3, and mean disease duration was 11.9 years at baseline. Mean baseline SDI was 1.64, and mean baseline SLICC Frailty Index was 0.18.

A total of 35.6% of patients were considered frail at baseline, 43% were least fit, and 21.6% were relatively fit.

The overall mean change in the SLICC Frailty Index at 5 years was -0.01. No clinically significant change at 5 years was observed for 47.7% of the patients, a clinically significant increase was seen in 21.5%, and a decrease was observed in 30.9%, the researchers reported.

At 5 years, 38.9% of patients showed increases of at least one point on the SDI, while the remainder had no increase in damage. Of the 58 patients with increases in SDI, the increase was one point in 33 patients, two points in 16, and three or more points in nine.

In a univariate analysis, no significant associations with damage at 5 years other than for baseline SLICC Frailty Index were seen for potential confounders including age, baseline disease activity or SDI, or medication use.

For the individual medications on the multivariate analysis, similar results to the primary outcome were seen for corticosteroid and antimalarial use, although a nonsignificant increase in risk for damage accrual was seen with immunosuppressant use (OR 1, 95% CI 0.81-1.28, P=0.98).

"The finding that frailty is a robust predictor of damage accrual in patients with longstanding SLE aligns with the concept that frailty arises via the accumulation of deficits within a complex network of interconnected elements, with greater deficit accumulation indicating a loss of physiologic reserve and increased susceptibility to future health threats," the researchers wrote.

They noted that the observation that baseline SDI failed to predict later damage in patients with established disease supported previous findings that damage tends to plateau later in the course of SLE -- typically after about 10 years.

"Unlike damage, frailty is reversible and future work should investigate how an individual's SLICC Frailty Index trajectory impacts health outcomes, as well as the potential usefulness of the [index] as an outcome measure in future SLE intervention studies," Ramsey-Goldman and co-authors concluded.

Limitations of the study, the team said, included the relatively small sample size and the enrollment of women only.

Comment