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Proposal 1695

Title of the Proposed Research

Outcome measures and baseline predictors of response to belimumab treatment.

Lead Researcher

Ioannis Parodis

Affiliation

Department of Medicine, Rheumatology Unit, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden

Funding Source

None. In case we apply for funding that is approved we will acknowledge the funding source(s) in the respective publications.

Potential Conflicts of Interest

Summary for all Researchers and Statistician
Ioannis Parodis has received honoraria (related to SLE) from GSK. Laurent Arnaud has received honoraria (related to SLE) from Amgen, Astra-Zeneca, GSK, Lilly, Pfizer, Roche, Springer. Ioannis Parodis has received honoraria (related to SLE) from GSK.

Data Sharing Agreement Date

21 September 2017

Lay Summary

Belimumab is a monoclonal antibody targeting the soluble form of B lymphocyte stimulator (BLyS) approved for the treatment of systemic lupus erythematosus (SLE). However, which patients are expected to best respond to this treatment has yet to be elucidated. In a recent report from real-life observations, high levels of BLyS have been implied to predict a good response while tobacco smoking and already established damage, previous venous thrombosis in particular, were shown to reduce the efficacy of the drug (Parodis I et al., Autoimmun Rev. 2017). A limitation of this report was the low number of patients observed. The phase III trials of belimumab constitute large cohorts of well-characterised patients with SLE receiving belimumab, and also provide a control group of patients receiving placebo facilitating comparisons. These cohorts could be used to validate the implications from the real-life observations, contributing to a better management of the patients with SLE and, more specifically, a better choice of patients who are expected to benefit from belimumab. Recently, a new definition was proposed for the characterisation of patients with low disease activity state, namely the lupus low disease activity state (LLDAS) (Franklyn K et al., Ann Rheum Dis. 2016). In the phase III clinical trials of belimumab, however, the SLE responder index (SRI) was used to identify responders to the treatment.

The aims of this project are to investigate whether measuring BLyS levels could provide physicians with guidance on whether belimumab is expected to be efficacious in specific cases, whether pre-existing organ damage predicts worse responses to treatment with belimumab, and whether tobacco smoking indeed reduces the efficacy of belimumab in larger SLE populations. Moreover, we aim to apply the more recent definition of lupus low disease activity state (LLDAS) and investigate whether belimumab is more effective than placebo in inducing low disease activity compared with the SLE responder index (SRI). The latter will contribute to the ongoing discussion about which definitions of response and low disease activity and/or remission are more applicable and more realistic to use in clinical trials and observational studies of SLE.

Either logistic or Cox regression models will be used to identify predictors of response and non-response to treatment with belimumab, and either regression models, mixed models, or the chi-square test will be used to investigate the rates of patients attaining LLDAS.

Experts in statistics will be consulted for the right choice of the tests. Experts in the field will participate in the interpretation of the results and their applicability and usefulness in clinical practice. Finally, the results and our conclusions will be communicated at scientific meetings and in research articles, which we will submit to scientific journals for peer review and publication.

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.