Background Systemic Lupus Erythematosus (SLE) is a heterogeneous disease that can cause multisystem inflammation and damage. There are currently no widely agreed upon targets for determining adequate disease control. Lupus Low Disease Activity State (LLDAS) is a new clinical evaluation tool that assesses low disease activity state in lupus patients (Franklyn, et al. Ann Rheum Dis. 2016; 75: 1615–1621). Our study examines the relationship between the percentage of time patients spend in LLDAS and organ damage accrual, cardiovascular events, and death.
Methods We studied a prospective cohort of 246 patients with SLE during a 5 year follow-up period. Disease activity was measured using the SLE Disease Activity Index 2000 (SLEDAI-2K) and SELENA-SLEDAI physician global assessment (PGA). Cumulative organ damage was assessed at 1 year, 3 year, and 5 year intervals using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). The determination of LLDAS 50% of the time for the year after cohort entry (LLDAS-50) was done retrospectively through clinical chart review. The following criteria for LLDAS included: SLEDAI-2K 4 without major organ activity, no new disease activity, PGA (0–3) 1, prednisone 7.5 mg/day and stable dose of maintenance treatments. The longitudinal presence of carotid plaque and intima-media thickness (IMT) was measured at baseline and follow-up three years later. We determined the relationships between LLDAS, SDI, IMT, carotid plaque, and PREDICTS profile using multivariate regression analysis.
Results The average age was 43.2 years for patients in LLDAS-50 and 39.5 years for those not in LLDAS-50 (p=0.03). Disease duration was 13.4 years for LLDAS 50% vs. 10.9 years for LLDAS<50% (p=0.04). Patients in LLDAS-50 or higher during the year after cohort entry had a mean SDI score of 1.5 (±1.8) at 1 year, a mean SDI of 1.6 (±1.9) at 3 years, and 1.9 (±2.1) at 5 years after cohort entry. On average, patients who were in LLDAS-50 during the first year after cohort entry had lower SDI scores at 3 years and 5 years than patients who were not, reaching significance (p=0.04) for both.
There was no significant difference in measured IMT or plaque between patients in LLDAS-50 and those not in LLDAS-50 for the first year after baseline. However, patients in LLDAS-50 were significantly less likely to have major cardiac events (major stroke, myocardial infarction, positive stress test, angioplasty or percutaneous coronary intervention) or death compared with patients who were not in LLDAS-50, 17.1% and 31.4%, respectively (p=0.01).
Conclusions With regard to damage progression, there was significantly less damage at 3 and 5 years among those in LLDAS 50% of the time during the first year after cohort entry. Interestingly, although there were no differences between IMT, presence of carotid plaque, or plaque progression at any of the three time points, there was a statistically significant difference in number of cardiovascular events or deaths in the LLDAS-50 group. This supports LLDAS as a valid predictor of lower overall and cardiovascular damage in SLE patients.
Funding Source(s): NCATS Grant No: UL1TR00188
NIH Grant No: 5R01AR063754-02
Correlation Between LLDAS and Cardiovascular Events or Death. Patients in LLDAS 50% of the time suffer from significantly fewer cardiovascular events or deaths than their non-LLDAS counterparts.
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