PO:15:217 | Improved efficacy and safety outcomes in patients with systemic lupus erythematosus treated with belimumab vs. immunosuppressants, in addition to antimalarials and glucocorticoids: a post-hoc summary of five phase 3 trials

Mariele Gatto¹, Karen H. Costenbader², Andreas Schwarting³, Julia Hn Harris⁴, Ciara O'Shea⁵, Roger A. Levy⁶, Andrea Doria⁷ | ¹Centro Accademico Reumatologia, Dipartimento Scienze Cliniche Biologiche, Università degli Studi Torino, Osp. Mauriziano, Italy; ²Brigham and Women's Hospital, Divisione di Reumatologia, Infiammazione e Immunità, Harvard Medical School, Boston, MA, USA; ³Università Johannes Gutenberg di Mainz, Centro medico universitario, Germany; ⁴GSK, Immunologia Biostatistica London, UK; ⁵GSK, Global Medical Affairs Reumatologia, Dublin, Ireland; ⁶GSK, Global Medical Affairs Collegeville, PA, USA; ⁷Divisione di Reumatologia, Dipartimento di Medicina, Università di Padova, Italy

Background. To assess efficacy and safety of BEL relative to being on IS at baseline, in combination with standard treatment (ST) which includes AM and GC, using pooled data from past clinical trials in patients with SLE.

Materials and Methods: This post hoc pooled Week 52 data for adults with active SLE from 5 Phase 3 trials (BLISS-52 [NCT00424476]; BLISS-76 [NCT00410384]; North East Asia [NCT01345253]; BLISS-SC [NCT01484496]; EMBRACE [NCT01632241]). In these studies, patients were randomised to receive BEL or placebo (PBO) in addition to ST. This summary grouped patients by study treatment: an IS cohort (receiving PBO and IS at baseline, defined as pre-treatment) and a BEL cohort (BEL 10 mg/kg IV or 200 mg SC, and no baseline IS); all patients received AM and GC at baseline. Efficacy endpoints included proportion of patients with SRI-4 response through 52 weeks, and cumulative GC dose (mg) between baseline and Week 52. Adverse events (AEs) and serious AEs (SAEs), also included data from an additional Phase 2 trial (LBSL02 [NCT00071487]).

Results: Of the pooled population (N=3086), 552 patients were in the BEL cohort and 358 in the IS cohort. Baseline characteristics were similar between cohorts (Table 1). A higher proportion of BEL patients vs IS patients were SRI-4 responders at most time points, with a difference of 22% at Week 52 between BEL (61%) and IS (39%) cohorts (Figure 1A). The mean (SD) cumulative GC dose decreased by −192 (2510.8) mg atWeek 52 in the BEL cohort and increased by 339 (4725.5) mg in the IS cohort (Figure 1B). Fewer patients had AEs and SAEs in the BEL vs IS cohort (AEs: 79% vs 90%; SAEs: 11% vs 20%), with one death reported in the BEL cohort (pneumonia; treatment-unrelated). Fewer patients in the BEL vs IS cohort discontinued treatment due to AEs (6% vs 8%). Most common AEs were infections and infestations (53% vs 64%). The most frequent SAEs were infections and infestations (BEL: 4% vs IS: 8%).

Conclusions: This post hoc summary adds clinical data supporting the benefits of initiating BEL in patients not receiving IS at baseline versus PBO and IS at baseline, in those not well controlled with AM and GC at baseline. Patients treated with BEL but not IS were also able to reduce GC dose even if taper was not mandated, and had fewer AEs.