Can a core set of disease activity domains define response in systemic lupus erythematosus clinical trials? An analysis of three Phase 3 randomised controlled trials of belimumab.

Can a core set of disease activity domains define response in systemic lupus erythematosus clinical trials? An analysis of three Phase 3 randomised controlled trials of belimumab.

Systemic lupus erythematosus (SLE), is an autoimmune disease in which the immune system attacks its own tissues, causing widespread inflammation and tissue damage in the affected organs. Disease activity in systemic lupus erythematosus (SLE) can affect virtually any part of the body, in different combinations in different patients, which makes measuring disease activity and response to treatment difficult. This is an important issue facing recent clinical trials in SLE, where there have been many challenges in understanding how effective new lupus treatments may be. Part of the issue is that the tools used to capture disease activity and response to treatment try to measure almost all manifestations that can occur in lupus. However, many of these manifestations are extremely rare, poorly defined, or very difficult to measure accurately, which compromises the accuracy with which clinical trials can distinguish how well new treatments work. We propose that measuring a smaller “core set” of active disease features in SLE may be a more effective approach in SLE clinical trials, focusing on the most common and measurable features. Other features that are very rare or difficult to measure accurately, could then be captured using simpler methods (such as a visual analogue scale of activity), with the purpose of ensuring important activity outside the "core set" is not missed. Our study aims to test this hypothesis and see whether responders in three previous belimumab clinical trials can be identified by measuring a smaller “core set” of disease features. This has the potential to make clinical trial measurement simpler, as well as making it more feasible to perform more detailed assessments of activity and treatment response for the lupus disease features most relevant for patients who enter clinical trials. Belimumab is a monoclonal antibody drug targeting B cell activating factor. It is an approved effective treatment for SLE, and one of only very few advanced treatments to have had efficacy successfully proven in clinical trials. The Phase 3 trials in which we propose to conduct our study represent the largest accessible clinical trial dataset in SLE, thus offering an ideal dataset to investigate our research question.

[{ "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)" },{ "PostingID": 19766, "Title": "GSK-BEL113750", "Description": "GSK1550188 A 52 week study of belimumab versus placebo in the treatment of subjects with systemic lupus erythematosus (SLE) located in Northeast Asia" }]