P67 The SLE-DAS enables easy identification of SLE patients with severe disease activity and worse health-related quality of life: derivation and validation in post-hoc study of anifrolumab phase 2 and 3 clinical trials

BackgroundAccurate and practical outcome measures for clinical trials in SLE are lacking.Objectives(i) To derive and validate the SLE-DAS cut-off value for defining severe disease activity (SDA); (ii) to evaluate if patients in SDA by SLE-DAS, SLEDAI-2K and BILAG-2004 present worse health-related quality of life (HR-QoL).MethodsPost-hoc analysis of aggregated intention-to-treat data from the placebo arms from MUSE, TULIP-1 and -2 trials (NCT01438489, NCT02446912 and NCT02446899) of anifrolumab versus placebo for moderate-to-severe SLE. We analyzed the BILAG-2004, SLEDAI-2K and the patient reported outcomes (PROs) [(LupusQoL, EQ-5D, FACIT-F and Patient Global Assessment (PtGA)]. The SLE-DAS was retrospectively scored. Derivation of the SLE-DAS cut-off for SDA, was performed using data from the MUSE and TULIP-2 trials at week 12, through bootstrap based method for ROC curve analysis against BILAG-2004 (numerical score >11). Performance of the SLE-DAS SDA cut-off was assessed using TULIP-1 trial data. We further compared the HR-QoL PROs between patients in SDA vs non-SDA by SLE-DAS, SLEDAI-2K (>12) and BILAG-2004, using Mann-Whitney test. The magnitude of these differences was compared using Cohen’s d.ResultsAt week 12, from 438 SLE patients, 46.6% and 42.4% were classified in SDA by BILAG-2004 in the derivation and validation cohorts, respectively. In the derivation cohort, the best cut-off to identify patients in SDA was SLE-DAS >9.90 (AUC=0.847, 95%CI:0.811–0.882). When applied in the validation cohort this cut-off showed a sensitivity =77.8% and a specificity =79.6%. Patients in SDA by SLE-DAS and BILAG-2004 presented significantly worse impact in all HR-QoL PROs (p