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Proposal 1343

Title of the Proposed Research

Improving the Assessment of Systemic Lupus Erythematosus Disease Activity

Lead Researcher

Zahi Touma

Affiliation

University of Toronto
University Health Network

Funding Source

GlaxoSmithKline

Potential Conflicts of Interest

Funding for this project is provided by GSK

Data Sharing Agreement Date

6 December 2016

Lay Summary

Lupus is an autoimmune disease which has the potential to cause inflammation and dysfunction in all organ systems of the body. Lupus has a worldwide distribution with a 9:1 female to male ratio and inflicts a high personal and societal cost. Research has improved our understanding of lupus, provided better diagnostic strategies and lead to better treatments. However, despite our advancements in understand lupus, physicians’ assessment of disease activity in lupus is very challenging.

Disease activity can be defined as a reversible state, manifested by clinical and laboratory features that are lupus specific. The grading of disease activity in clinical practice or in research settings is essential in patient care and can be achieved with the application of disease activity instruments. The Systemic Lupus Erythematosus Disease Activity Index (SLEDAI-2K) is one of the most commonly used disease activity indices. Clinical trials experience suggested disease activity instruments did not function well on their own and composite measures were developed to address this issue. This approach has been adopted after learning from clinical trials that the absence of a robust sensitive index is a major flaw when designing a trial. Another issue with clinical trials is the confounding effect of corticosteroids, which to date have been the most effective treatment for the management of lupus. However, unregulated use of corticosteroids in drug trials decrease our ability to differentiate between the tested drugs and placebo as they appear to enhance response among the placebo arm and thus mask the effect of the tested drug.

In this study we aim to develop and validate a new index, SLEDAI-2K Steroid Index (SSI). It is very challenging to evaluate improvement in drug trials in the context of the standard of care treatment which includes corticosteroids. This novel index, SSI will help to overcome the confounding effect of corticosteroids and to allow for more accurate description of disease improvement and thus facilitate accurate investigations of new therapeutic agents.

Objectives: To describe the development and initial validation of theSLEDAI-2K Steroids Index (SSI) using the Toronto Lupus Cohort (TLC) database; to conduct further validation of SSI using BLISS trial data and to assess concurrent construct validity of SSI prospectively in the University of Toronto Lupus Clinic.

Objective one is a single center study aiming to derive a new index, SSI, based on SLEDAI-2K. Scoring of SSI will be determined in this study. Objective two is a retrospective analysis conducted on prospectively collected data from two clinical trials, BLISS-52 and BLISS-76. Objective three is a single centre prospective study.

Multiple abstracts and manuscripts will result from this project corresponding to each objective.

Study Data Provided

GSK-HGS1006-C1056: 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)
GSK-HGS1006-C1057: 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)

Statistical Analysis Plan

Publication Citation

The publication citation will be added after the research is published.

Summary Results

Results summary or link will be posted when available.