Background: Belimumab (BEL), a monoclonal antibody that antagonizes B-lymphocyte stimulator, was first approved in 2011 for active, autoantibody-positive systemic lupus erythematosus (SLE). BEL has been studied for over 10 years; and while safety data from individual trials have been informative, a large integrated safety analysis has not yet been conducted.

Objectives: Perform pooled analyses to evaluate the safety of BEL in adult patients with SLE.

Methods: Aggregate analyses were performed using safety data for patients ≥18 years of age pooled from six randomised, placebo (PBO)-controlled BEL clinical trials (GSK studies: LBSL02, 110752, 110751, 112341, 113750, and 115471). Patients from GSK studies LBSL02, 110752, and 110751 received intravenous (IV) BEL 1, 4 (LBSL02 only), or 10 mg/kg, or PBO on Days 1, 14, 28, and every 28 days thereafter. Patients from GSK studies 113750 and 115471 received IV BEL 10 mg/kg or PBO on Days 1, 14, 28, and every 28 days thereafter. Patients from GSK study 112341 received subcutaneous (SC) BEL 200 mg, or PBO weekly. Safety analyses included the incidence of adverse events (AEs), serious AEs (SAEs), severe AEs, AEs of special interest (AESI), and mortality of BEL (all doses and formulations combined) vs PBO at Week 52.

Results: The pooled analysis included 4170 patients. Overall, 81.0% (n=2280/2815) of patients receiving BEL and 76.6% (n=1038/1355) of patients receiving PBO completed their respectively enrolled study; the most common reason for withdrawal was occurrence of an AE in both groups. The majority of patients were female (BEL: 94.5%; PBO: 93.6%), the mean age in both groups was 38 years, and baseline characteristics (race, SLE duration, disease activity, SLE damage, complement levels, anti-dsDNA binding, SLE medication usage) were similar between treatments.

The incidence of patients experiencing ≥1 AE, ≥1 SAE, and mortality was similar across treatments ( Table 1 ); the most commonly reported SAEs in both groups were infections and infestations (BEL: 5.4% [n=151/2815]; PBO: 5.9% [n=80/1355]). The mean duration of treatment exposure was similar between groups (BEL: 334.1 days; PBO: 325.3 days).

A greater proportion of patients experienced AESI with BEL vs PBO for post-infusion/injection systemic reactions (from IV or SC administration) and depression/suicide/self-injury ( Table 1 ). The proportion of patients experiencing an AESI of infections and malignancies was similar between groups.

Conclusion: Consistent with individual studies, BEL demonstrated a similar safety profile to PBO in this large integrated safety analysis of six trials. These results support a positive benefit–risk profile of BEL in the treatment of adult SLE.

Funding: GSK

Acknowledgements: Medical writing assistance was provided by Helen Taylor, Fishawack Indicia Ltd., UK, part of Fishawack Health, and was funded by GSK.

Disclosure of Interests: Daniel J. Wallace Speakers bureau: GSK, Consultant of: GSK, Tatsuya Atsumi Speakers bureau: GSK, Consultant of: GSK, Grant/research support from: GSK, Mark Daniels Shareholder of: GSK, Employee of: GSK, Anne Hammer Shareholder of: GSK, Employee of: GSK, Paige Meizlik Shareholder of: GSK, Employee of: GSK, Holly Quasny Shareholder of: GSK, Employee of: GSK, Andreas Schwarting Speakers bureau: Novartis, Roche, GSK, Pfizer, Amgen, Consultant of: GSK, Grant/research support from: AbbVie, Pfizer, Novartis, GSK, Actelion, Fengchun Zhang: None declared, David Roth Shareholder of: GSK, Employee of: GSK