SLE-DAS responder index: a novel outcome measure with high performance for physician and patient outcomes in anifrolumab phase 2-3 trials.

Abstract

The objectives of this study were to develop and evaluate the performance of the novel SLE-DAS Responder Index (RI) as an efficacy end point in SLE trials, and to assess the utility of SLE-DAS in identifying moderate-to-severe disease activity (MSDA). This post-hoc analysis pooled data from the placebo arms of three randomized controlled trials of anifrolumab (MUSE, TULIP-1, and TULIP-2). The SLE-DAS RI was defined as a reduction in SLE-DAS of ≥1.72 and a score of ≤7.64 at week 52. Associations between SLE-DAS RI and changes in disease activity, glucocorticoid exposure, and health-related quality of life (HR-QoL) were evaluated using regression models. The predictive performance of SLE-DAS RI for HR-QoL was compared with the BILAG-based Composite Lupus Assessment (BICLA) and the SLE Responder Index (SRI-4). Flare occurrence was analysed using the SLE-DAS flare tool and Cox regression. The ability of SLE-DAS to identify MSDA was assessed at screening and week 12, using BILAG-2004 and SLEDAI-2K as comparators. Of 438 patients, 34.0% achieved SLE-DAS RI response at week 52. Responders showed greater reductions in disease activity, lower cumulative glucocorticoid exposure, and significantly improved HR-QoL. Multiple linear regression identified SLE-DAS RI response as the most significant predictor of HR-QoL improvements across multiple domains. SLE-DAS RI responders had 41.9% lower risk of flare. At screening, SLE-DAS MSDA identified 96.1% of patients with MSDA and better reflected HR-QoL burden at week 12. The SLE-DAS RI is a robust efficacy end point in SLE trials, associated with sustained disease control and meaningful improvements in patient-reported outcomes. SLE-DAS also enables accurate identification of MSDA, supporting its broader utility in trial design.