Lupus Low Disease Activity State (LLDAS), defined as a disease state associated with a low probability of irreversible organ damage, has been adopted as an attainable endpoint for lupus treatment to replace the often-unachievable state of remission. It has therefore been recently identified as a potential treat-to-target goal in systemic lupus erythematosus (SLE), a complex disease with poorly defined and typically unattainable endpoints (e.g., remission). In this study, Hopkins investigators sought to determine the time to LLDAS attainment in a group of lupus patients and identify useful predictors of achieving this low disease state.
Why was this study done?
Lupus low disease activity state (LLDAS) has been associated with reduced SLE-induced damage and mortality, and has therefore been proposed as a promising treat-to-target goal in SLE. This study was untaken to determine whether time to attainment of LLDAS is a feasible target endpoint for clinical trials and treat-to-target goal to prevent early organ damage. The researchers additionally sought to identify meaningful patient characteristics to act as predictors of time to LLDAS attainment, including the effect of ethnicity.
How was this study done?
1,426 patients enrolled in the Johns Hopkins Lupus Cohort, who had not achieved LLDAS prior to entry into the cohort, were analyzed prospectively by following patient disease development to determine the time to LLDAS attainment. In this cohort, LLDAS was defined as a low overall disease activity score with no major organ involvement (e.g., kidneys, central nervous system, heart, lungs, and gastrointestinal system), no persistently active disease, and low steroid usage, among other criteria, while time to LLDAS was defined as the time between cohort entry and the first clinic visit at which LLDAS was attained. Patient characteristics such as ethnicity, disease duration, medications, and disease biomarkers were investigated for an association with time to LLDAS attainment.
What were the major findings?
The study found that patients were able to attain LLDAS within a median of 1.1 years from cohort entry. The probability of LLDAS attainment within one year was 52% for Caucasians, but just 36% for African-Americans. In an analysis of baseline characteristics of the entire cohort, disease duration of less than one year, taking less than 10 mg of prednisone daily, taking hydroxychloroquine, and having normal levels of disease biomarkers were associated with faster achievement of LLDAS. Conversely, African-American ethnicity and baseline renal activity or damage were associated with later attainment. Among African-Americans, those taking >10 mg prednisone with low complement levels and baseline renal activity took longer to attain low disease activity state.
What is the impact of the work?
Most patients in the study achieved LLDAS within 5 years of cohort entry with a median time to LLDAS of 1.1 years, confirming the feasibility of LLDAS as a target endpoint for randomized clinical trials. LLDAS was further validated as an attainable treat-to-target goal to prevent early organ damage in SLE for both Caucasian and African-American patients. Finally, the study highlighted the stark ethnic disparities in SLE outcomes, particularly for African-American SLE patients who were found to take longer to achieve LLDAS and who are typically underrepresented in SLE clinical trials. The researchers therefore emphasize the importance of including African-Americans and patients of other ethnicities in clinical trials and research studies to account for disparate disease outcomes.
This research supported by:
- NIH AR 43727
Time to Lupus Low Disease Activity State in the Hopkins Lupus Cohort: Role of African‐American Ethnicity Hakan Babaoglu, Jessica Li, Daniel Goldman, Laurence S Magder, Michelle Petri
First published: 10 September 2019 https://doi.org/10.1002/acr.24063