Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2022 Nov;31(13):1649-1659.
doi: 10.1177/09612033221131183. Epub 2022 Oct 7.

Safety of belimumab in adult patients with systemic lupus erythematosus: Results of a large integrated analysis of controlled clinical trial data

Daniel J Wallace  1 , Tatsuya Atsumi  2 , Mark Daniels  3 , Anne Hammer  4 , Paige Meizlik  5   6 , Holly Quasny  7 , Andreas Schwarting  8 , Fengchun Zhang  9 , David A Roth  10
Affiliations
Randomized Controlled Trial

Safety of belimumab in adult patients with systemic lupus erythematosus: Results of a large integrated analysis of controlled clinical trial data

Daniel J Wallace et al. Lupus. 2022 Nov.

Abstract

Objectives: Systemic lupus erythematosus (SLE) is a chronic, autoimmune disease that affects multiple organ systems. Belimumab, a targeted human monoclonal antibody, binds to and inhibits soluble B-lymphocyte stimulator. The safety and efficacy of belimumab has consistently been demonstrated in multiple clinical trials for the treatment of patients with active SLE. Integration of these data provides an additional opportunity to explore the safety of belimumab in a larger and more diverse population. This post hoc pooled analysis of clinical studies evaluated the safety profile of belimumab versus placebo in adults with SLE.

Methods: This was a pooled post hoc analysis of 52-week safety data from one Phase 2 and five Phase 3 belimumab trials in adult patients with SLE. Patients received ≥1 dose of placebo or belimumab (1, 4, or 10 mg/kg intravenous or 200 mg subcutaneous), plus standard therapy. Outcomes included the incidence of adverse events (AEs), serious AEs (SAEs), severe AEs, AEs of special interest (AESI), and mortality.

Results: Across 4170 patients (placebo: N = 1355; belimumab: N = 2815), baseline demographics, disease characteristics, and treatment exposure were similar for placebo and belimumab. Most patients (placebo: 76.6%; belimumab: 81.0%) completed the protocol Week 52 visit. Overall, incidence of AEs, SAEs, severe AEs, AESI, and mortality were similar between groups. In both groups, the most commonly reported SAEs by system organ class were infections and infestations (placebo: 5.9%; belimumab: 5.4%) and renal and urinary disorders (placebo: 2.2%; belimumab: 1.7%). Additionally, a greater proportion of patients experienced AESI with belimumab versus placebo for post-infusion/injection systemic reactions (placebo: 8.1%; belimumab: 10.2%). Mortality rates were similar between groups (placebo: 0.4%; belimumab: 0.6%).

Conclusions: These results are consistent with those of the individual studies, BASE, BLISS-LN, and long-term extension studies, making belimumab one of the most studied SLE treatments for safety. Collectively, this evidence continues to support a positive benefit-risk profile of belimumab in the treatment of adult patients with SLE.

Keywords: autoimmune diseases; belimumab; biological products; safety; systemic lupus erythematosus.

PubMed Disclaimer

Conflict of interest statement

The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: DJW has worked as a consultant and has been a paid speaker for GSK. TA has received financial grants from GSK, and has been a consultant and a paid speaker for GSK. MD, AH, HQ, and DAR are employees of GSK and hold stocks and shares in the company. PM was an employee of GSK and held stocks and shares in the company at the time of the study. AS has received financial grants from GSK, AbbVie, Actelion, Novartis, and Pfizer, has been a paid consultant for GSK, and has been a paid speaker for GSK, Amgen, Novartis, Pfizer, and Roche. FZ has been a paid speaker for GSK and has taken part in a GSK advisory board.

Figures

Figure 1.
Figure 1.
Overview of the studies included in the pooled safety analysis population.– *The current analysis used Week 52 safety data from all studies. However, the treatment period of BLISS-76 was 72 weeks. †4 mg/kg for Study LBSL02 only. Five Phase 3 trials and one Phase 2 trial (LBSL02) were included. IV: intravenous; SC: subcutaneous.
Figure 2.
Figure 2.
Summary of AEs, SAEs, and mortality in the pooled safety analysis population by treatment group. AE: adverse event; SAE: serious adverse event.
See this image and copyright information in PMC

References

    1. Fanouriakis A, Kostopoulou M, Alunno A, et al. 2019 update of the EULAR recommendations for the management of systemic lupus erythematosus. Ann Rheum Dis 2019; 78: 736–745. - PubMed
    1. Tunnicliffe DJ, Singh-Grewal D, Kim S, et al. Diagnosis, monitoring, and treatment of systemic lupus erythematosus: a systematic review of clinical practice guidelines. Arthritis Care Res (Hoboken) 2015; 67: 1440–1452. - PubMed
    1. Touma Z, Gladman DD. Current and future therapies for SLE: obstacles and recommendations for the development of novel treatments. Lupus Sci Med 2017; 4: e000239. - PMC - PubMed
    1. Tamirou F, Husson SN, Gruson D, et al. Brief report: the Euro-lupus low-dose intravenous cyclophosphamide regimen does not impact the ovarian reserve, as measured by serum levels of anti-Mullerian hormone. Arthritis Rheumatol 2017; 69: 1267–1271. - PubMed
    1. Hsu CY, Lin MS, Su YJ, et al. Cumulative immunosuppressant exposure is associated with diversified cancer risk among 14.832 patients with systemic lupus erythematosus: a nested case-control study. Rheumatology (Oxford) 2017; 56: 620–628. - PubMed

Publication types