AB0288 SAFETY OF BELIMUMAB IN PATIENTS WITH ACTIVE SYSTEMIC LUPUS ERYTHEMATOSUS: YEAR 2 FOLLOW-UP OF A LARGE PHASE 4, RANDOMISED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY
Authors: S. Sheikh, M. Scheinberg, J. C. C. Wei, D. Tegzová, W. Stohl, T. Mucenic, R. Punwaney, R. Kurrasch, J. Harris, S. Muzaffar, S. Fernandes, N. L. Fox, A. Liu, H. Quasny, D. Roth
Journal: Annals of the Rheumatic Diseases (2021)

Background: Belimumab (BEL), a recombinant human monoclonal antibody that inhibits B-lymphocyte stimulator (BLyS), is approved for the treatment of systemic lupus erythematosus (SLE). Clinical studies have yielded varying incidence rates of mortality and adverse events of special interest, such as malignancies, thereby necessitating large-scale, long-term assessment following BEL exposure. Objectives: To assess all-cause mortality and new primary malignancies during post-treatment Year 2 follow-up in adult patients with active, autoantibody-positive SLE who received intravenous (IV) BEL or placebo (PBO), plus standard therapy in the 52-week double-blind treatment period of the ongoing BASE trial. 1 Methods: This was a post-treatment follow-up of the Phase 4, double-blind study (BASE 1 ; GSK Study BEL115467; NCT01705977 ), which randomised 4019 adults with active SLE and receiving standard therapy to BEL (10 mg/kg IV) or PBO on Days 0, 14, 28, and monthly thereafter until Week 48. All patients (including those who discontinued BEL before the end-of-treatment phase) were contacted by phone annually (+/-30-day time window). Rates of mortality and new primary malignancy are summarised for Year 2 follow-up, presented by the treatment received during the 52-week double-blind treatment period (Year 1). Results: Baseline patient characteristics and disease activity collected at the start of the study, evaluated in patients with Year 2 follow-up were similar to the overall Year 1 study population. Cumulatively by Year 2 follow-up, 10.7% and 9.5% of patients had been exposed to commercial BEL in the BEL and PBO groups, respectively. Cumulative follow-up adjusted mortality and malignancy rates (per 100 patient years) were lower in the BEL vs PBO Year 1 treatment group (Table 1). Conclusion: Year 2 follow-up results of BASE, the largest clinical trial of SLE to date, 1 provide continued support for the BEL safety profile. No new BEL safety concerns were identified in patients with active, autoantibody-positive SLE receiving standard therapy. Funding: GSK References: [1]Sheikh SZ, et al. Lancet Rheum . 2020 (ePub ahead of print) doi.org/10.1016/S2665-9913(20)30355-6 Table 1. Year 2 post-treatment* follow-up mortality and new primary malignancy rates by study treatment during Year 1 BEL PBO Total Year 1 as-treated population N=2002 N=2001 N=4003 Year 1 deaths, n (%) 13 (0.65) 22 (1.10) 35 (0.87) Year 1 new primary malignancies, n (%) 9 (0.45) 10 (0.50) 19 (0.47) Year 2 (as-treated in Year 1) population N=1681 N=1666 N=3347 Year 2 deaths by MedDRA SOC, n (% ) 9 (0.54) 21 (1.26) 30 (0.90) Cardiac disorders 2 (0.12) 6 (0.36) 8 (0.24) Infections and infestations 4 (0.24) 2 (0.12) 6 (0.18) Uncoded 1 (0.06) 3 (0.18) 4 (0.12) General disorders/administration site conditions 1 (0.06) 2 (0.12) 3 (0.09) Gastrointestinal disorders 1 (0.06) 1 (0.06) 2 (0.06) Neoplasms 0 2 (0.12) 2 (0.06) Other 0 5 (0.30) † 5 (0.15) Cumulative deaths by Year 2 follow-up, n (% ) 22 (1.10) 43 (2.15) 65 (1.62) Incidence rate per 100 patient years 0.60 1.18 0.89 Year 2 new primary malignancies by MedDRA SOC, n (% ) 3 (0.18) 4 (0.24) 7 (0.21) Neoplasms 2 (0.12) 4 (0.24) 6 (0.18) Hepatobiliary disorders 1 (0.06) 0 1 (0.03) Cumulative malignancies by Year 2 follow-up, n (% ) 12 (0.60) 14 (0.70) 26 (0.65) Patient incidence rate per 100 patient years 0.34 0.40 0.37 *Patients in the post-treatment follow-up period are no longer receiving study treatment; † 1 event/patient: blood/lymphatic system, musculoskeletal/connective tissue, nervous system, psychiatric, and renal/urinary disorders. MedDRA, Medical Dictionary for Regulatory Activities; SOC, system organ class. Acknowledgements: Medical writing assistance was provided by Katalin Bartus, PhD, Fishawack Indicia Ltd., UK, part of Fishawack Health, and was funded by GSK. Disclosure of Interests: Saira Sheikh Grant/research support from: Pfizer, Morton Scheinberg Consultant of: GSK, Pfizer, Alnylam, AbbVie, PTC Therapeutics, James Cheng-Chung Wei Consultant of: TSH Biopharm, AbbVie, BMS, Celgene, Chugai, Eisai, Janssen, Novartis, Pfizer, Sanofi-Aventis and UCB pharma, Grant/research support from: AbbVie, Amgen, Astellas, BMS, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer Sun and UCB, Dana Tegzová: None declared, William Stohl Consultant of: GSK, Grant/research support from: GSK, Pfizer, Gilead, Tamara Mucenic Speakers bureau: Novartis, Janssen, BMS, AbbVie, Pfizer, Roche, Grant/research support from: GSK, Janssen, Roche, Eli Lilly, Gilead, UCB, Raj Punwaney Shareholder of: GSK, Employee of: GSK, Regina Kurrasch Shareholder of: GSK, Employee of: GSK, Julia Harris Shareholder of: GSK, Employee of: GSK, Saima Muzaffar Shareholder of: GSK, Employee of: GSK, Sofia Fernandes Shareholder of: GSK, Employee of: GSK, Norma Lynn Fox Shareholder of: GSK, Employee of: GSK, Andrew Liu Shareholder of: GSK, Employee of: GSK, Holly Quasny Shareholder of: GSK, Employee of: GSK, David Roth Shareholder of: GSK, Employee of: GSK