POS0696 SAFETY AND EFFICACY OF BELIMUMAB IN OLDER ADULTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS: RESULTS OF AN INTEGRATED ANALYSIS

Abstract

Background:Systemic lupus erythematosus (SLE) is a chronic, autoimmune disease characterised by persistent B-cell activation. Belimumab (BEL), a monoclonal antibody that inhibits B-lymphocyte stimulator, is approved in patients aged ≥5 years with active autoantibody-positive SLE; however, safety and efficacy data of BEL in older adults are limited.Objectives:Assess the safety and efficacy of BEL in older adults with SLE.Methods:A meta-analysis (GSK study 116559) was performed on the subpopulation of patients aged ≥65 years and compared with the overall population pooled from six controlled, repeat-dose (CRD) BEL trials in adults with SLE (GSK studies: 110752, 110751, LBSL02 [safety only], 112341, 113750, and 115471). Additional safety data were obtained from GSK study 115467.In each trial, patients were randomised to BEL or placebo (PBO) and received ≥1 treatment dose (GSK studies 110752 and 110751: intravenous [IV] BEL 1 or 10 mg/kg; LBSL02: IV BEL 1, 4, or 10 mg/kg; GSK study 112341: subcutaneous BEL 200 mg; GSK studies 113750, 115471, and 115467: IV BEL 10 mg/kg) plus standard therapy. Safety assessments included: incidence of serious adverse events (SAE), mortality and adverse events of special interest (AESI). The primary efficacy analysis for the CRD trials was the SLE Responder Index 4 (SRI4) response rate.Results:Older adults (CRD studies: N=63; study 115467: N=156) had lower disease activity and more organ damage compared with the overall populations, and a greater proportion were of white race compared with the overall population in the CRD studies. There were no clinically relevant differences in the incidence of SAE or death between older adults and the overall populations (Table 1). Rates of AESI (post-infusion/injection systemic reactions [PISR], serious infections of special interest, malignancies, psychiatric events) were generally similar or lower in older adults compared with the overall populations with no imbalances between BEL and PBO in older adults (Table 1). No malignancies were reported in older adults. The SRI4 response rate in older adults favoured BEL vs PBO (OR [95% CI], 1.49 [0.49, 4.58]), consistent with the overall populations of the individual CRD studies (110752 and 110751 pooled [10 mg/kg IV]: 1.68 [1.32, 2.15]; 112341: 1.68 [1.25, 2.25]; 113750: 1.99 [1.40, 2.82]; 115471: 1.42 [0.94, 2.15]).Conclusion:In patients with SLE, the safety and efficacy of BEL in older adults were generally consistent with the overall population and suggest a favourable benefit–risk profile. Due to the small number of older adults analysed, these data should be interpreted with caution.Funding:GSKTable 1.SAE, deaths, and AESIN (%)*Study 115467CRD studies†Older adults(N=156)Overall(N=4003)Older adults(N=63)Overall(N=4170)PBON=82BELN=74PBON=2001BELN=2002PBON=27BELN=36PBON=1355BELN=2815SAE9 (11.0)6 (8.1)222 (11.1)220 (11.0)5 (18.5)10 (27.8)230 (17.0)421 (15.0)Death‡1 (1.2)1 (1.4)11 (0.5)12 (0.6)006 (0.4)16 (0.6)AESI PISR§,‖,¶----02 (5.6)110 (8.1)286 (10.2) Serious PISR002 (<0.1)8 (0.4)002 (0.1)13 (0.5)Infections of SI (opportunistic, herpes zoster, tuberculosis, sepsis)§02 (2.7)50 (2.5)36 (1.8)1 (3.7)097 (7.2)173 (6.1)Serious infections of SI02 (2.7)17 (0.8)17 (0.8)0017 (1.3)40 (1.4)Malignancies ex. non-melanoma skin cancer§005 (0.2)5 (0.2)002 (0.1)8 (0.3)Depression(inc. mood disorders /anxiety)/suicide/self-injury§,¶,**-‖---3 (11.1)3 (8.3)92 (6.8)210 (7.5)Serious depression/ suicide/self-injury01 (1.4)6 (0.3)18 (0.9)1 (3.7)05 (0.4)9 (0.3)*Patients counted once/category; †Pooled data from all studies except 115467; ‡Study 115467: fatal SAEs that started during on-treatment period; death may have occurred after period end. CRD studies: all deaths during double-blind period; §Per custom MedDRA query; ‖Occurring on/within 3 days of infusion/injection; ¶Study 115467: only serious PISR and serious depression/suicide/self-injury events collected; **Per standard MedDRA query.MedDRA, Medical Dictionary for Regulatory Activities; SI, special interestAcknowledgements:Medical writing assistance was provided by Helen Taylor, Fishawack Indicia Ltd., UK, part of Fishawack Health, and was funded by GSK.Disclosure of Interests:David d’cruz Speakers bureau: GSK, Consultant of: GSK, Eli Lilly, Gina Eriksson Shareholder of: GSK, Employee of: GSK, Yulia Green Shareholder of: GSK, Employee of: GSK, Anne Hammer Shareholder of: GSK, Employee of: GSK, Beulah Ji Shareholder of: GSK, Employee of: GSK, Paige Meizlik Shareholder of: GSK, Employee of: GSK, David Roth Shareholder of: GSK, Employee of: GSK