Abstract
Background Adoption of treat to target approaches for Systemic Lupus Erythematosus (SLE) requires the definition of a target state validated for improved patient outcomes. The Lupus Low Disease Activity State (LLDAS) has been shown in multiple retrospective and cross-sectional studies to have face, content, construct and criterion validity and be associated with better quality of life. We report on a multinational prospective study undertaken to determine whether LLDAS attainment is associated with protection from flare and damage accrual.
Methods A prospective multinational cohort study was undertaken in 13 centres between 2013–2017. Patients with SLE were recruited, SLEDAI-2k, SELENA flare index, PGA, and medication data collected at every visit, and damage (SLICC-ACR damage index (SDI)) collected annually. Time-dependent Cox proportional hazards models were used to assess the association of LLDAS at any time point, as well as the effect of the proportion of time spent in LLDAS, with disease flare and damage accrual (increase in SDI).
Results 1735 patients were followed for (mean ±SD) 2.2±0.9 years, totalling 12 717 visits. LLDAS was achieved in 54.6% of visits. Attainment of LLDAS at any timepoint was associated with reduction in subsequent flare (HR 0.65, 95% CI 0.56–0.76, p<0.001) and damage accrual (HR 0.55, 95% CI 0.43–0.70, p<0.001). Similarly, patients who spent 50% of their observed time in LLDAS had reduction in risk of flare (RR 0.41, p<0.001) and damage accrual (RR 0.59, p<0.001), compared to those with <50% of observed time in LLDAS. Increased durations of sustained LLDAS were associated with incremental reduction in risk of damage accrual. The protective association of LLDAS with reduced damage accrual was maintained in subgroup analysis of patients with active disease at baseline (SLEDAI-2K>6) or pre-existing damage (SDI>0).
Conclusions LLDAS attainment provides significant protection against disease flare and damage accrual thereby supporting its use as a treatment target in SLE, and as an outcome measure for clinical trials and treat-to-target strategies.
Funding Source(s): The Asia Pacific Lupus Collaboration receives project support grants from UCB, GlaxoSmithKline, Janssen, Bristo-Myers Squibb, and AstraZeneca.
