Systemic Lupus Erythematosus Disease Activity Score (SLE-DAS) validation: post-hoc analysis of the BLISS-52 and BLISS-76 phase III trials.

Systemic Lupus Erythematosus Disease Activity Score (SLE-DAS) validation: post-hoc analysis of the BLISS-52 and BLISS-76 phase III trials.

Background: The Systemic Lupus Erythematosus (SLE) Responder Index (SRI) is the most used primary endpoint in recent SLE clinical trials. In the SRI, the SLE Disease Activity Index (SLEDAI) is the core determinant of clinical response. However, the SLEDAI has a limited performance to detect clinically meaningful changes in disease activity, because it scores each item dichotomously as present or absent and as a result only detects total resolution of any manifestation. In fact, SLEDAI totally overlooks partial improvement in any individual lupus manifestation, even if it implies a major clinical change. This limitation has important implications in assessing the efficacy of new drugs and may justify the failure of most promising lupus clinical trials.Recently, our research group derived and validated a new continuous measure of lupus disease activity, the SLE Disease Activity Score (SLE-DAS), with improved sensitivity to detect a clinically meaningful change in lupus disease activity and higher performance in predicting damage accrual, as compared to SLEDAI. SLE-DAS can thus provide a highly sensitive measure for detecting disease activity improvement and to accurately quantify the effect size of interventions. However, there is a need to further validate SLE-DAS in international, multiethnic SLE populations. Study objectives: (i) To evaluate the performance of SLE-DAS to detect a clinically meaningful change in lupus disease activity in BLISS-52 and -76 trials; (ii) To determine the ability of SLE-DAS to discriminate between placebo and belimumab treatment groups; (iii) To evaluate the association between SLE-DAS and health-related quality of life (HRQoL).Study design: Post-hoc analysis of aggregated data from the phase III, multicenter, placebo-controlled BLISS-52 and -76 trials, which jointly provide a large multiethnic, international study population. SLE-DAS will be calculated across all study time points and compared with the other endpoint measures that were prospectively obtained in these clinical trials and required for this study project. Data analysis: Descriptive statistics will be used to summarize demographic variables, disease measures, manifestations, and pharmacological treatment. Data analysis for the objectives of this study will be done, in order to evaluate the performance of SLE-DAS compared to SRI and other clinical parameters of interest. Changes in clinical and laboratory measures and pharmacological treatment from baseline to last observation, between SLE-DAS responders and non-responders, will be assessed using univariate and multivariate statistical techniques chosen according to the type of data and fulfillment of statistical assumptions.Expected results: We aim to further validate the SLE-DAS, comparing it to major indexes of disease activity and HRQoL patient-reported outcomes. Furthermore, we will explore the performance of SLE-DAS as an alternative to SRI as a primary outcome measure for SLE clinical trials.

[{ "PostingID": 1416, "Title": "GSK-HGS1006-C1056", "Description": "A Phase 3, Multi-Center, Randomized, Double-Blind, Placebo-Controlled, 76-Week Study to Evaluate the Efficacy and Safety of Belimumab (HGS1006, LymphoStat-B™), a Fully Human Monoclonal Anti-BLyS Antibody, in Subjects with Systemic Lupus Erythematosus (SLE)" },{ "PostingID": 1417, "Title": "GSK-HGS1006-C1057", "Description": "A Phase 3, Multi-Center, Randomized, Double-Blind, Placebo-Controlled, 52-Wk Study to Evaluate the Efficacy and Safety of Belimumab (HGS1006, LymphoStat-B™), a Fully Human Monoclonal Anti-BLyS Antibody, in Subjects With Systemic Lupus Erythematosus (SLE)" }]