Pos0733 Validation of the Sle-Das Responder Index as an Accurate and Feasible Endpoint for Sle Clinical Trials: A Post-Hoc Study in the Phase 2 and 3 Anifrolumab Clinical Trials

Background: Accurate and practical outcome measures for clinical trials in Systemic lupus erythematosus (SLE) are lacking. Currently used primary endpoint measures (i.e. the SRI and BICLA) include over 120 items, are cumbersome to score and not feasible in the clinical setting. 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 1,2. The new SLE-DAS Responder Index (SLE-DAS RI) may provide an outcome measure with high performance and feasibility. The SLE-DAS RI has 17 items and defines a responder as: decrease in SLE-DAS ≥1.72 and no moderate/severe disease activity (SLE-DAS score ≤7.64). Objectives: To evaluate the performance of the SLE-DAS RI to identify improvement in clinical and laboratory aspects of SLE, and in health-related quality of life (HR-QoL) patient reported outcomes (PROs). Methods: Post-hoc analysis of the aggregated intention-to-treat, placebo arm participants, in the anifrolumab versus placebo for moderate-to-severe SLE phase 2 and 3 RCTs MUSE (NCT01438489), TULIP-1 (NCT02446912), TULIP-2 (NCT02446899). We analyzed the physicians' assessments including clinical and analytical data, BILAG-2004, CLASI-A, SLEDAI-2K and Physician Global Assessment (PhGA), the patient reported outcomes (PROs) LupusQoL, SF-36, EQ-5D, FACIT-F and Patient Global Assessment (PtGA) scores and the cumulative glucocorticoid intake. The SLE-DAS score was retrospectively assessed from the individual participants' data. Disease activity was categorized as severe (SLE-DAS >9.90), moderate (SLE-DAS >7.64 to ≤9.90) or mild/remission (SLE-DAS ≤7.64) and the fulfillment of SLE-DAS response was assessed (defined as a decrease in SLE-DAS ≥1.72 + SLE-DAS score ≤7.64). Changes from study baseline to week 52 in clinical, laboratory and HR-QoL PROs were compared among SLE-DAS responders versus non-responders using logistic regression and linear regression models adjusted for baseline scores. Results: We assessed 438 SLE patients. At week 52, 34% (n=149) of the patients achieved a SLE-DAS response, presenting significantly lower disease activity measured by SLE-DAS, SLEDAI-2K and PhGA (Table 1 and Figure 1). None of the SLE-DAS responders presented activity in major organ systems, including the central nervous system, cardiopulmonary, renal, vasculitis, gastrointestinal or hemolytic anaemia). Only 2% (n=3) and 0.6% (n=1) presented ≥1 new BILAG A/B domain and an increase in PhGA ≥0.3 points, respectively. Importantly, the SLE-DAS responders had significantly lower glucocorticoid use during the study follow-up. Additionally, SLE-DAS responder presented significantly higher improvements in all aspects of HR-QoL PROs, namely the LupusQoL, SF-36, EQ-5D, FACIT-F and PtGA. Conclusion: Achievement of SLE-DAS response is associated with significant improvements both in the physician measures of disease activity and the HR-QoL PROs as compared to non-responders. The SLE-DAS RI provides an accurate and feasible endpoint for SLE clinical trials. REFERENCES: 1 Jesus D, Matos A, Henriques C, et al. Derivation and validation of the SLE Disease Activity Score (SLE-DAS): a new SLE continuous measure with high sensitivity for changes in disease activity. Ann Rheum Dis 2019;78:365-71. 2 Jesus D, Larosa M, Henriques C, et al. Systemic Lupus Erythematosus Disease Activity Score (SLE-DAS) enables accurate and user-friendly definitions of clinical remission and categories of disease activity. Ann Rheum Dis 2021;80:1568-74. Acknowledgements: This publication is based on research using data from data contributors AstraZeneca that has been made available through Vivli, Inc. Vivli has not contributed to or approved, and is not in any way responsible for, the contents of this publication. Disclosure of Interests: None declared.