Abstract
Background Accurate 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).
Methods Post-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.
Results At 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<0.0001 and p<0.001, respectively) (table 1). In contrast, patients in SDA by SLEDAI-2K did not present significantly severe impact in EQ-5D, FACIT-F, PtGA and 5/8 domains of LupusQoL. Notably, the SLE-DAS SDA presented numerically higher effect sizes for all HR-QoL PROs, as compared to BILAG-2004 and SLEDAI-2K.
Conclusion The SLE-DAS is an easy-to-use tool for identifying patients in SDA. The SLE-DAS SDA identifies patients with worse HR-QoL, thus enabling good agreement between the physicians’ and patients’ perspectives. This study suggests that SLE-DAS SDA may present higher ability to discriminate patients with worse aspects of HR-QoL.
Acknowledgement 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.
