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Outcome measures and baseline predictors of response to belimumab treatment.








Outcome measures and baseline predictors of response to belimumab treatment.


Ioannis Parodis


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


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


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.


21 September 2017


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.



[{ "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, Sponsor: GSK"},{"PostingID":20307,"Title":"GSK-BEL114333","Description":"A Phase 3, BEL114333, a Multicenter, Continuation Study of Belimumab in subjects with Systemic Lupus Erythematosus (SLE) who Completed the Phase III study BEL113750 in Northeast Asia or completed the open-label extension of HGS1006-C1115 in Japan, Sponsor: GSK"},{"PostingID":14488,"Title":"GSK-HGS1006-C1115","Description":"A Phase 3, Multi-Center, Randomized, Double-Blind, Placebo-Controlled, 52-Week Study to Evaluate the Efficacy and Safety of Belimumab (HGS1006) Administered Subcutaneously (SC) to Subjects with Systemic Lupus Erythematosus (SLE), Sponsor: GSK"},{"PostingID":19767,"Title":"GSK-BEL112233","Description":"A Multi-Center, Continuation Trial of Belimumab (HGS1006, LymphoStat-B™), a Fully Human Monoclonal Anti-BLyS Antibody, in Subjects with Systemic Lupus Erythematosus (SLE) who Completed the Phase 3 Protocol HGS1006-C1056 in the United States, Sponsor: GSK"},{"PostingID":20055,"Title":"GSK-BEL112234","Description":"A Multi-Center, Continuation Trial of Belimumab (HGS1006, LymphoStat-B™)a Fully Human Monoclonal Anti-BLyS Antibody in Subjects with Systemic Lupus Erythematosus (SLE) who completed the Phase 3 Protocol HGS1006-C1056 or HGS1006-C1057, Sponsor: GSK"}]

Statistical Analysis Plan


Ioannis Parodis, Sharzad Emamikia, Alvaro Gomez, Iva Gunnarsson, Ronald F. van Vollenhoven & Katerina Chatzidionysiou
(2018): Clinical SLEDAI-2K zero may be a pragmatic outcome measure in SLE studies, Expert Opinion on Biological Therapy,

https://www.tandfonline.com/doi/full/10.1080/14712598.2019.1561856

http://dx.doi.org/10.1136/annrheumdis-2018-214880

https://academic.oup.com/rheumatology/advance-article/doi/10.1093/rheumatology/kez191/5510116?guestAccessKey=3ad38e37-5e79-460f-af2b-37672a291dee

Antimalarial agents diminish while methotrexate, azathioprine and mycophenolic acid increase BAFF levels in systemic lupus erythematosus. Hernández-Breijo B, Gomez A, Soukka S, Johansson P, Parodis I.
Autoimmun Rev. 2019 Aug 10:102372. doi:
10.1016/j.autrev.2019.102372

https://doi.org/10.1016/j.autrev.2019.102372