Background/Purpose: Belimumab (BEL) is a disease-modifying systemic lupus erythematosus (SLE) treatment that inhibits B-lymphocyte stimulator. BEL has demonstrated a consistent efficacy profile across 4 pivotal Phase 3 trials^1-4 and has improved renal outcomes in active LN and reduced SLE organ damage progression^5,6. In 2011, BEL became the first biologic approved for SLE treatment in the USA⁷ with additional approvals in >70 countries. Severe flares in SLE are linked to poor long-term outcomes and increased healthcare resource utilization⁸. BEL has been shown to decrease severe flare risk²; however, data are lacking for specific patient (pt) subgroups. This analysis evaluated the role of BEL in preventing severe flares across a large pooled population as well as by subgroups.

Methods: The B­elimumab Summary of Lupus Efficacy (Be-SLE) analysis assessed data from 5 double-blind, placebo (PBO)-controlled BEL studies: BLISS-76, BLISS-52, BLISS-NEA, BLISS-SC, and EMBRACE. Data from pts receiving BEL (10 mg/kg intravenously or 200 mg subcutaneously) were compared with PBO; both groups received also standard therapy (ST). Data were collected every 4 weeks from baseline until Week 52. Severe flare was defined using the Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA)-SLE Disease Activity Index (SLEDAI) flare index. The number of pts and time to first severe flare (days) were determined for both groups. Time to first severe flare was evaluated by the following subgroups: SLE International Collaborating Clinics (SLICC)/American College of Rheumatology (ACR) Damage Index (SDI) score, disease duration, anti-double stranded deoxyribonucleic acid (dsDNA), serum levels of C3 and C4 proteins, steroid use, and immunosuppressant use. Hazard ratios (HR) for severe flare risk between groups were calculated using Cox proportional hazards model, adjusted for study and baseline SELENA-SLEDAI score.

Results: The analysis included 1869 pts receiving BEL and 1217 pts receiving PBO. Mean age (~37 years) and percentage of females (~94%) were similar between treatment groups. Over 52 weeks, 13.8% (n=258) of pts receiving BEL had severe flares versus 22.2% (n=270) of pts receiving PBO. BEL yielded a 39% reduction in the risk of severe flares versus PBO (HR: 0.61; 95% confidence interval [CI]: 0.51, 0.72). BEL also consistently reduced the risk of severe flares versus PBO across various pt subgroups (Figure); risk reductions appeared greater in pts with anti-dsDNA+ and ≥C3/C4, or SDI=0.

Conclusion: Pts receiving BEL had a reduced risk of severe flares versus pts receiving PBO. Some subgroups had greater risk reduction; these pts in particular may benefit from BEL. These results reinforce the advantage of BEL in ST in the treatment of SLE.

Funding: GSK

References:

¹Navarra SV, et al. Lancet 2011;377(9767):721–31

²Furie RA, et al. Arthritis Rheum 2011;63(12):3918–30

³Zhang F, et al. Ann Rheum Dis 2018;77(3):355–63

⁴Stohl W, et al. Arthritis Rheum 2017;69(5):1016–27

⁵Urowitz MB et al. Ann Rheum Dis 2019;78(3):372–9

⁶Furie R, et al. N Engl J Med. 2020;383(12):1117-1128.

⁷GlaxoSmithKline. Benlysta Prescribing Information 2021

⁸Garris C et al. J Med Econ. 2013;16(5):667–77

Figure: Risk of severe flares HR for BEL versus PBO for various pt characteristic subgroups AM, antimalarial; ISA, immunosuppressant The orange box denotes the 95% CI for the overall (intention-to-treat) HR

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/belimumab-reduces-severe-flares-in-systemic-lupus-erythematosus-across-multiple-patient-subgroups-results-of-a-large-integrated-analysis/