POS0119 SLE-DAS REMISSION AND LOW DISEASE ACTIVITY STATES ARE ASSOCIATED WITH IMPROVED HEALTH-RELATED QUALITY OF LIFE AND FATIGUE: POST-HOC ANALYSIS OF THE BLISS-52 AND BLISS-76 PHASE III TRIALS.

Abstract

Background: Accurate and practical outcome measures for clinical trials in systemic lupus erythematosus (SLE) are lacking. The SLE Disease Activity Score (SLE-DAS) is a recently validated 17-item instrument, with high accuracy and sensitivity to changes in SLE disease activity. The SLE-DAS defnitions of remission and low disease activity (LDA) were newly validated against disease activity physician-applied measures in the clinical setting [1, 2]. Criterion validity of SLE-DAS for Patient Reported Outcomes, namely health-related quality of life (HR-QoL) and fatigue needs to be assessed. Objectives: To evaluate if the attainment of SLE-DAS remission and LDA states is associated with improvements in HR-QoL and fatigue. Methods: Post-hoc analysis of the merged study population in the BLISS-52 and-76 trials (NCT00424476; NCT00410384) of intravenous belimumab versus placebo for moderate to severe SLE disease activity. We analysed the Functional Assessment of Chronic Illness Therapy (FACIT) and 36-Item Short Form Survey (SF-36) trial data. Fulfllment of SLE-DAS remission (defned as absence of all SLE-DAS clinical items and prednisone ≤5mg/day) and LDA (defned as SLE-DAS≤2.48 and prednisone ≤7.5mg/day) defnitions were retrospectively assessed from the individual participants' data. Mean changes from study baseline to week 52 in FACIT and SF-36 physical component summary (PCS) and mental component summary (MCS) and domain scores were compared between patients attaining at week 52 the SLE-DAS remission vs non-remission and the SLE-DAS LDA vs non-LDA using multivariate regression analysis adjusted for baseline scores. Results: A total of 1684 SLE patients were included. Few patients were in SLE-DAS remission (0.5%) and LDA (0.8%) at study entry. At week 52, 12.5% patients attained SLE-DAS remission and 17.5% attained SLE-DAS LDA. Mean improvements in SF-36 PCS and MCS scores were greater in patients that attained SLE-DAS remission vs non-remission (5.4 vs 3.4, and 4.6 vs 2.7, respectively; multivariate p<0.005 for both) and SLE-DAS LDA vs non-LDA (5.0 vs 3.4 and 4.6 vs 2.6, respectively; multivariate p<0.005 for both), at week 52 (Figure 1). Similarly, improvements in all individual domain scores were greater in SLE-DAS remission vs non-remission patients (all multivariate p<0.005) and SLE-DAS LDA vs non-LDA patients (all multivariate p<0.005) (Figure 1). Importantly, improvements in the summary scores and in all the individual domain scores largely exceeded the minimum clinically important differences (MCIDs) of 2.5 and 5 points, respectively, in those patients attaining SLE-DAS remission or LDA. Additionally, mean improvements in FACIT scores were higher in SLE-DAS remission than non-remission (6.3 vs 3.6, multivariate p<0.001) and in SLE-DAS LDA than non-LDA (5.9 vs 3.6, multivariate p<0.001), and exceeded the MCID of 4 points. Conclusion: Attainment of SLE-DAS remission and LDA is associated with meaningful improvement in HR-QoL and fatigue.