Lupus Activity Affects Mortality Save

Each one-unit increase on a disease activity score during the first year after enrollment into a systemic lupus erythematosus (SLE) cohort was associated with a significant increased risk for death and organ damage during subsequent follow-up, researchers reported.

On a multivariable analysis, a one-unit increase on the Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA) version of the SLE Disease Activity Index (SLEDAI) was associated with a 22% higher risk of death during an average 7 years of follow-up (HR 1.22, 95% CI 1.13-1.32, P<0.001) after adjustment for age, sex, race, duration of disease, and use of high-dose prednisone, according to Michelle A. Petri, MD, of Johns Hopkins University School of Medicine in Baltimore, and colleagues.

In addition, among patients with no organ damage at baseline, each one-unit increase on the SELENA-SLEDAI during the first year after entrance into the Hopkins Lupus Cohort was associated with an increased risk in overall organ damage during the subsequent 7 years (HR 1.09, 95% CI 1.04-1.15, P<0.001), which was a relatively short follow-up time, the researchers reported online in Lupus Science & Medicine. However, treatment with hydroxychloroquine significantly reduced the likelihood of damage.

Survival rates have risen dramatically in recent decades, but irreversible organ damage remains an important concern, with patients who have organ damage being likely to develop more damage, thus lessening their likelihood of survival.

Therefore, to explore the current pattern of damage accrual among patients with SLE in a racially diverse study population, Petri's group analyzed data from their cohort, including 1,168 patients enrolled from 1987 to 2010. Patients with at least 2 years of follow-up were included in the analysis.

Disease activity was assessed at each quarterly clinic visit, along with data on medication use, comorbidities, and damage to the renal, cardiovascular, peripheral vascular, pulmonary, neuropsychiatric, and musculoskeletal systems.

More than 90% of patients were women, 55% were white, and 39% were of Black African ancestry.

Median age at cohort enrollment was 36. The mean adjusted SELENA-SLEDAI was 3 during the first year after enrollment, with 55% of patients having mild-to-moderate disease activity, defined as a SELENA-SLEDAI below 3.

Medication use included oral prednisone in 60.1% of the patients, oral prednisone in daily doses above 7.5 mg in 36.6%, hydroxychloroquine in 65%, nonsteroidal anti-inflammatory drugs (NSAIDs) in 38.3%, and immunosuppressants in 22.4%.

A total of 8% of patients died during follow-up, but the use of hydroxychloroquine was associated with a 54% lower risk of death (HR 0.46, 95% CI 0.29-0.72, P<0.05).

Among patients without organ damage at the outset, 39% developed damage during follow-up. There were no differences in the risk of damage when the analysis was stratified by race.

During follow-up, 3% of patients without renal damage at baseline developed this organ damage, and each one-unit increase in adjusted mean SELENA-SLEDAI was associated with a 24% increased risk of renal damage (HR 1.24, 95% CI 1.08-1.42, P=0.003). Having ever been treated with hydroxychloroquine lowered the likelihood of renal damage by 70% (HR 0.30, 95% CI 0.13-0.68, P<0.05), the researchers reported.

Among patients with no cardiovascular damage at the time of enrollment, 7% subsequently developed this type of damage, and each one-unit increase in SELENA-SLEDAI was associated with a 17% higher risk (HR 1.17, 95% CI 1.07-1.29, P<0.001). However, patients who used NSAIDs were found to have a 66% increased risk of cardiovascular damage (HR 1.66, 95% CI 1.04-2.63, P<0.05).

Moreover, patients who were treated with antihypertensives had an 81% greater risk of cardiovascular damage (HR 1.81, 95% CI 1.09-3.02, P<0.05).

The findings of increased cardiovascular damage with NSAID and antihypertensive use "may suggest that the known cardiovascular risk of NSAIDs in the general population is also applicable to patients with SLE and highlights the importance of assessing cardiovascular risk in this patient population," Petri and colleagues wrote.

Changes in SELENA-SLEDAI did not influence the risk for damage among other organ systems, including the peripheral vascular, pulmonary, and neuropsychiatric systems.

The study confirmed that even minor fluctuations in disease activity in patients with mild-to-moderate disease "underscore the need for active measures to manage SLE disease activity over time," the authors concluded.

A limitation of the study, they noted, was that it was performed at a single tertiary center.

Source Reference: Hill D, et al "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 center" Lupus Sci Med 2021; doi:10.1136/lupus-2020-000446.