SLE-DAS enables an accurate definition of severe lupus disease activity: derivation and validation in a post hoc study of anifrolumab phase II and III studies

Abstract

Objectives: This study aimed to derive and validate a cut-off for severe disease activity (SDA) using the SLE Disease Activity Score (SLE-DAS) and compare its accuracy and impact on health-related quality of life (HR-QoL) with the British Isles Lupus Assessment Group 2004 (BILAG-2004) and SLE Disease Activity Index 2000 (SLEDAI-2K).

Methods: We performed a post hoc analysis of pooled placebo arm data from the MUSE (A Phase II, Randomized Study to Evaluate the Efficacy and Safety of MEDI-546 in Subjects with Systemic Lupus Erythematosus), TULIP-1 and TULIP-2 (Treatment of Uncontrolled Lupus via the Interferon Pathway) trials, including 438 patients with moderate-to-severe SLE. SLE-DAS was scored retrospectively, and a cut-off for SDA was derived using receiver operating characteristic (ROC) curves against the BILAG-2004 numerical score >11 as gold standard. Multiple linear regression analysis and Cohen's d effect size were applied to evaluate the effectiveness of SLE-DAS, BILAG-2004 and SLEDAI-2K SDA classifications in capturing HR-QoL patient-reported outcomes (PROs).

Results: The optimal SLE-DAS cut-off for SDA was >9.90 (area under the ROC curve=0.847, sensitivity=77.8%, specificity=79.6%). Patients classified as SDA by both SLE-DAS and BILAG-2004 or only by SLE-DAS exhibited similar disease activity, while those classified by BILAG-2004 alone had less severe disease and better HR-QoL. The SLE-DAS cut-off was associated with worse HR-QoL across multiple PROs more consistently than BILAG-2004 or SLEDAI-2K.

Conclusion: The SLE-DAS cut-off for SDA provides an accurate definition of SDA in SLE, with good discriminative power and consistent associations with worse HR-QoL. This SLE-DAS definition enhances disease activity classification and offers a practical tool for guiding treatment decisions in clinical practice, as well as selecting patients with SDA for inclusion in clinical trials.

Keywords: Health-Related Quality Of Life; Outcomes research; Systemic Lupus Erythematosus.

Figure 1. Comparison of Lupus Quality of Life domain scores of patients fulfilling the severe disease activity (SDA) definition by SLE Disease Activity Score (SLE-DAS) and British Isles Lupus Assessment Group 2004 (BILAG-2004) with those classified as SDA only by SLE-DAS (but not BILAG-2004) or only by BILAG-2004 (but not SLE-DAS) at week 12. The height of the bars represents the mean values, and the number in each bar of the graph represents the median and the IQRs are listed below. P values were calculated using the Mann-Whitney U test.

Figure 2. Health-related quality of life patient-reported outcomes among patients fulfilling the severe disease activity (SDA) definition by SLE Disease Activity Score (SLE-DAS) and British Isles Lupus Assessment Group 2004 (BILAG-2004) and those in SDA only by SLE-DAS (but not BILAG-2004) or only by BILAG-2004 (but not SLE-DAS) at week 12. (A) Comparison of Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-F). (B) Comparison of Patient Global Assessment. (C) Comparison of EuroQol 5 Dimension (EQ-5D) visual analogue scale (VAS). (D) Comparison of the EQ-5D index. The height of the bars represents the mean values, and the numbers inside the bars represent the median and the IQRs. P values were calculated using the Mann-Whitney U test.

Figure 3. Health-related quality of life patient-reported outcomes among patients classified as severe disease activity (SDA) and non-SDA according to SLE Disease Activity Score (SLE-DAS) at week 12. The radial chart (A) illustrates the comparisons of Lupus Quality of Life (LupusQoL) mean domain scores; the bar charts (B), (C), (D) and (E) illustrate the comparisons of Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-F), Patient Global Assessment, EuroQol 5 Dimension (EQ-5D) visual analogue scale (VAS) and EQ-5D index, respectively. The height of the bars represents mean scores, while the whiskers represent SD. P values were calculated using the Mann-Whitney U test, and Cohen’s d was assessed to compare the magnitude of these differences.