To assess the impact of mild-moderate systemic lupus erythematosus (SLE) disease activity during a 12-month period on the risk of death or subsequent organ system damage.

1168 patients with ≥24 months of follow-up from the Hopkins Lupus Cohort were included. Disease activity in a 12-month observation period was calculated using adjusted mean Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA) version of the SLE Disease Activity Index (SLEDAI), defined as the area under the curve divided by the time interval. Damage accrual in the follow-up period was defined as change in Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) score ≥1 among patients without prior damage. Patients visited the clinic quarterly and had SELENA-SLEDAI and SDI assessed at every visit.

During follow-up (median 7 years), 39% of patients accrued new damage in any organ system (7% cardiovascular and 3% renal) and 8% died. In adjusted models, an increased SELENA-SLEDAI score increased the risk of death (HR=1.22, 95% CI 1.13 to 1.32, p<0.001), renal damage (HR=1.24, 95% CI 1.08 to 1.42, p=0.003) and cardiovascular damage (HR=1.17, 95% CI 1.07 to 1.29, p<0.001). Hydroxychloroquine use reduced the risk of death (HR=0.46, 95% CI 0.29 to 0.72, p<0.05) and renal damage (HR=0.30, 95% CI 0.13 to 0.68, p<0.05). Non-steroidal anti-inflammatory drug use increased the risk of cardiovascular damage (HR=1.66, 95% CI 1.04 to 2.63, p<0.05). Without prior damage, an increased adjusted mean SELENA-SLEDAI score increased the risk of overall damage accrual (HR=1.09, 95% CI 1.04 to 1.15, p<0.001).

Each one-unit increase in adjusted mean SELENA-SLEDAI during a 12-month observation period was associated with an increased risk of death and developing cardiovascular and renal damage.