Among patients with systemic lupus erythematosus (SLE), increased adjusted mean scores of the Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA) version of the SLE Disease Activity Index (SLEDAI) may be associated with risk for death and development of cardiovascular and renal damage, according to study results published in Lupus Science & Medicine.

In the last 40 years, the 5-year survival in patients with SLE has increased to 95%, with 10-year survival rates following similar trends; however, irreversible damage to organ systems is still a major concern among patients with SLE because of accrual of additional damage and death. Results from previous studies have suggested that disease activity can predict SLE prognosis and survival.

To determine the effects of mild to moderate SLE disease activity on the risk for death or organ system damage, a team of researchers conducted an analysis using the SELENA-SLEDAI score to measure disease activity over a 12-month period.


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Patients with a clinical diagnosis of SLE who had at least a 24-month follow-up were included in the study. Follow-up was divided into a background period (the first 12 months after cohort entry), an observation period (the second 12 months after cohort entry), and the follow-up period (the remaining time until organ damage or death). At every clinic visit, disease activity was measured using the SELENA-SLEDAI score and damage accrual was measured using the Systemic Lupus International Collaborating Clinics (SLICC) and the American College of Rheumatology (ACR) Damage Index (SDI).

A total of 1168 patients (92.9% women; 55.1% White) were included in the current analysis. During the observation period, obesity, hypertension, and diabetes therapy (with oral hypoglycemic agents or insulin) were noted 51.7%, 55.8%, and 10.1% of the population, respectively; 54.9% of patients had an adjusted mean SELENA-SLEDAI score of less than 3 in the background period. Median adjusted mean SELENA-SLEDAI score in the observation and follow-up periods was 2 (range, 0-13).

During the follow-up period, 7.9% of patients died, and after 7 years of follow-up, adjusted mean SELENA-SLEDAI score of 5 or more significantly increased the risk for death (log rank P <.001). Results from a multivariable model suggested that every 1-unit increase in the adjusted mean SELENA-SLEDAI score during the observational period was linked to a 22% increase in the risk for death in the follow-up period (hazard ratio [HR], 1.22; P <.001). In addition, the use of hydroxychloroquine during the observation period was linked to a 54% reduction in the risk for death during the follow-up period (HR, 0.46; P <.05).

Of the 888 patients who did not have an overall history of organ system damage, 38.5% of patients developed organ damage (SDI ≥1) by the end of the follow-up period. After adjustment, multivariable models suggested that a 1-unit increase in adjusted mean SELENA-SLEDAI in the observation period was linked to an increased risk of accumulating further organ damage (HR, 1.09; P <.001), especially among women who did not have previous organ damage (HR, 1.08, P =.002).

Of the 1147 patients who did not have renal damage in the observation period, 2.7% developed renal damage in the follow-up period. During the observation period, every 1-unit increase in mean adjusted SELENA-SLEDAI increased renal damage by 24% in the follow-up period (HR, 1.24; P =.003). Hydroxychloroquine use in the observation period reduced the risk for renal damage in the follow-up period by 70% (HR, 0.30; P <.05).

Cardiovascular damage was reported in 6.5% of 1135 patients in the follow-up period, and every 1-unit increase in mean adjusted SELENA-SLEDAI during the observation period was linked with a 17% increase in the risk of accruing additional cardiovascular damage (HR, 1.17; P <.001). During the observation period, patients who were prescribed nonsteroidal anti-inflammatory (NSAID) drug therapies or any antihypertensive medications had 66% and 81% increases, respectively, in the risk for accrued cardiovascular damage (HR, 1.66; antihypertensives; HR, 1.81). 

“This analysis demonstrates that, even in patients with [mild to moderate] disease activity, an increase in adjusted mean SELENA-SLEDAI score and NSAID use during a 12-month period increases the risk [for] death and organ specific damage, highlighting the need for more active measures to manage SLE disease activity over time and to limit NSAID use,” the researchers concluded.

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.

Reference

Hill DD, Eudy AM, Egger PJ, Fu Q, Petri MA. Impact of systemic lupus erythematosus disease activity, hydroxychloroquine and NSAID on the risk of subsequent organ system damage and death: analysis in a single US medical centre. Lupus Sci Med. 2021;8(1):e000446. doi:10.1136/lupus-2020-000446