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Impact of belimumab on antiphospholipid antibodies in patients with Systemic Lupus Erythematosus
Proposal
5862
Title of Proposed Research
Impact of belimumab on antiphospholipid antibodies in patients with Systemic Lupus Erythematosus
Lead Researcher
Katerina Chatzidionysiou
Affiliation
1st Department of Propaedeutic and Internal Medicine, Laiko Hospital, Medical School, National and Kapodistrian University of Athens, Greece
Funding Source
Potential Conflicts of Interest
Data Sharing Agreement Date
24 April 2019
Lay Summary
Antiphospholipid antibody syndrome (commonly called antiphospholipid syndrome or APS) is an autoimmune disease present mostly in young women. Those with APS make abnormal proteins called antiphospholipid autoantibodies in the blood. This causes blood to flow improperly and can lead to dangerous clotting in arteries and veins, problems for a developing fetus and pregnancy miscarriage. People with this disorder may otherwise be healthy, or they also may suffer from an underlying disease, most frequently systemic lupus erythematosus (commonly called lupus or SLE).APS affects women five times more commonly than men. It is typically diagnosed between the ages of 30 and 40. While up to 40% of patients with SLE will test positive for the anti-phospholipid autoantibodies, only half will develop thrombosis and/or experience miscarriages. Belimumab is a biologic treatment approved by FDA and EMA for the treatment of SLE. It has been shown that it reduces the titers of autoantibodies found in SLE patients, such as antibodies against dsDNA. However, its impact on antiphospholipid antibodies has not been studied. If treatment with belimumab would be shown to reduce the titers of antiphospholipid antibodies, that might have impact on clinical practice.
Study Data Provided
[{ "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)" }]
Statistical Analysis Plan
First we will characterise patients tested positive for anti-phospholipid antibodies at baseline by means of descriptive statistics, with regard to demographics, disease and treatment characteristics. We will calculate the median (IQR) of the titer of antiphospholipid antibodies at baseline and at all available time-points during follow-up, and we will examine any significant reduction in the belimumab arm and in the placebo arm by Wilcoxon signed-rank test. We will then perform linear regression analysis in order to examine the difference between the belimumab and the placebo arm while adjusting for potential confounders (baseline differences, treatment, etc). We will also assess the frequency of seroconversion, that is the % of patients who tested positive for anti-phospholipid antibodies at baseline and who tested negative at follow-up. By chi-square test we will compare the % of patients who seroconverted in the belimumab arm and in the placebo arm. Logistic regression analysis will also be performed to adjust for potential confounders. We will undertake intention to treat analysis as the main analysis and per-protocol analysis as a sensitivity analysis.
Publication Citation
Chatzidionysiou K, Samoli E, Sfikakis PP, et alEffect of belimumab treatment on antiphospholipid antibody levels: post-hoc analysis based on two randomised placebo-controlled trials in systemic lupus erythematosus Annals of the Rheumatic Diseases 2020;79:304-307.
http://dx.doi.org/10.1136/annrheumdis-2019-216367
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