Maria Dall'Era1, Andrea Fava2, Christine Henning3, Angela R Jones-Leone4, Angela S Carroll5, Julia H N Harris6, Anne E Hammer7, Roger A Levy4, Laurence S Magder8 and Michelle Petri2, 1University of California, Division of Rheumatology, San Francisco, CA, 2Johns Hopkins University School of Medicine, Division of Rheumatology, Baltimore, MD, 3GlaxoSmithKline, Global Medical Affairs, Durham, NC, 4GlaxoSmithKline, Global Medical Affairs, Collegeville, PA, 5GlaxoSmithKline, US Medical Affairs, Research Triangle Park, NC, 6GlaxoSmithKline, Immunology Biostatistics, Brentford, United Kingdom, 7GlaxoSmithKline, Immunology Biostatistics, Collegeville, PA, 8University of Maryland, Department of Epidemiology and Public Health, Baltimore, MD
Background/Purpose: BEL, an approved SLE treatment,1 improved kidney outcomes in initial Phase 3 SLE trials.2,3 This post hoc analysis evaluates the effect of BEL on kidney outcomes in patients (pts) with SLE across a large, integrated population.
Methods: The BEL Summary of Lupus Efficacy (Be-SLE) post hoc analysis evaluated data (collected every 4 weeks [wks]; baseline [BL] to Wk 52) from adults with SLE from 5 BEL trials: BLISS-76, BLISS-52, BLISS-NEA, BLISS-SC, and EMBRACE (GSK Studies BEL110751, BEL110752, BEL113750, BEL112341, and BEL115471). Pts received BEL (10 mg/kg/month intravenously or 200 mg/wk subcutaneously) or placebo (PBO), plus standard therapy. Time to first kidney flare (defined in Table 1), SELENA-SLEDAI and BILAG kidney improvement and worsening, and kidney biomarker changes were assessed.
Results: Among 3086 pts (BEL, N=1869; PBO, N=1217), most were female (94.4%); mean (SD) age was 37.0 (11.64) years. Mean (SD) SLE duration was 6.4 (6.36) years. BL medication use was similar across groups. By Wk 52, 18.8% of BEL and 23.7% of PBO pts had withdrawn from the study.
Over 52 wks, fewer BEL vs PBO pts had ≥1 kidney flare in the overall population (4.5% vs 6.4%; hazard ratio, HR [95% confidence interval, CI]: 0.58 [0.42, 0.78]; p=0.0005) and in pts with BL proteinuria >0.5 g/24 hr (BEL, n=461; PBO, n=292; 12.4% vs 18.5%; HR [95% CI]: 0.53 [0.37, 0.78]; p=0.0011; Table 1). Among pts with a kidney flare, BEL vs PBO pts had a shorter median (interquartile range, IQR) time to first flare in the overall population (118 [57, 226] days vs 127 [85, 254] days) and among pts with BL proteinuria >0.5 g/24 hr (92 [57, 222] days vs 112 [57, 170] days).
Among pts with BL SELENA-SLEDAI kidney involvement (SELENA-SLEDAI score >0; BEL, n=319; PBO, n=233), significantly more BEL vs PBO pts had kidney improvement at Wk 52 (53.3% vs 40.3%; p=0.0033; Figure 1A); among pts with no BL kidney involvement (SELENA-SLEDAI score =0; BEL, n=1550; PBO, n=984), there was no significant difference in kidney worsening between groups (6.5% vs 7.0%; p=0.6241; Figure 1B). Among pts with BL kidney BILAG =A/B (BEL, n=249; PBO, n=165), there was no significant difference in kidney improvement (BILAG A score change to B/C/D/E, or from B to C/D/E) between groups at Wk 52 (58.2% vs 55.2%; p=0.5446; Figure 1C); among pts with BL kidney BILAG =B/C/D/E (BEL, n=1846; PBO, n=1207), significantly fewer BEL vs PBO pts had kidney worsening (BILAG B/C/D/E score change to A/B) at Wk 52 (12.4% vs 19.8%; p< 0.0001; Figure 1D).
At Wk 52, in the overall population, significantly fewer BEL vs PBO pts had a ≥30% estimated glomerular filtration rate (eGFR) reduction (2.1% vs 3.1%; p=0.0463), while the proportion of pts with ≥30% serum creatinine (sCr) increase was similar (5.6% vs 5.5%; p=0.5703; Table 2). In pts with BL proteinuria >0.5 g/24 hr, more BEL vs PBO pts shifted to ≤0.5 g/24 hr (45.0% vs 33.7%).
Conclusion: Favorable kidney outcomes were observed for BEL vs PBO in pts with SLE, including fewer kidney flares, greater kidney improvement (SELENA-SLEDAI), less kidney worsening (BILAG), and improved eGFR.
Funding: GSK
References 1GlaxoSmithKline. Benlysta US prescribing information. 2021 2Dooley MA, et al. Lupus. 2013;22:63–72 3Manzi S, et al. Ann Rheum Dis. 2012;71:1833–8 <img src=https://www.abstractscorecard.com/uploads/Tasks/upload/17574/QHOPTGBB-1290194-1-ANY.jpg width=440 height=293.24644549763 border=0 style=border-style: none;>
Figure 1. Kidney improvement* among pts with defined BL kidney organ system involvement† (A: SELENA-SLEDAI, C: BILAG), and kidney worsening‡ among pts without defined BL kidney organ system involvement (B: SELENA-SLEDAI, D: BILAG)
*Kidney improvement by SELENA-SLEDAI is defined as a decrease in kidney SELENA-SLEDAI score compared with BL. Kidney improvement by BILAG is defined as a kidney BILAG score change from A to B/C/D/E, or B to C/D/E; †kidney involvement is defined as either a SELENA-SLEDAI score >0 in the kidney organ system, or as a BILAG kidney score of A/B at BL; ‡kidney worsening by SELENA-SLEDAI is defined as an increase in SELENA-SLEDAI kidney score compared with BL; kidney worsening by BILAG is defined as a kidney score change from B to A, or from C/D/E to A/B. Treatment groups were compared using Fisher’s exact test. SE, standard error
Table 1. Time to first kidney flare* over 52 wks in the overall population (BEL, Nf1869; PBO, Nf1217) and among pts with BL proteinuria >0.5 g/24 hr (BEL, n=461; PBO, n=292)
*Kidney flare was defined as the development of ≥1 of the following 3 factors: increased proteinuria (reproducible increase in 24 hr urine protein levels to >1.0 g if BL value was < 0.2 g, >2 g if BL value was 0.2–1.0 g, or more than twice the value at BL if BL value was >1.0 g), impaired kidney function (reproducible increase in sCr of >20% or an increase of at least 0.3 mg/dL/reproducible >20% decrease in GFR, accompanied by proteinuria [>1.0 g/24 hr], hematuria [≥4 RBCs/hpf], and/or cellular [RBC and WBC] casts), and new hematuria (11–20 RBCs/hpf or a reproducible increase in hematuria by 2 grades vs BL, associated with >25% dysmorphic RBCs [glomerular in origin, exclusive of menses] accompanied by an 800 mg increase in 24 hr urinary protein levels or new RBC casts). In the EMBRACE study, new hematuria was not required; †a Cox proportional hazards model was used for the comparison between treatment groups, adjusting for study and BL SELENA-SLEDAI score (≤9 vs ≥10); ‡among pts who experienced a kidney flare in the overall population (BEL, n=85; PBO, n=78) and among pts with BL proteinuria >0.5 g/24 hr (BEL, n=57; PBO, n=54). hpf, high power field; RBC, red blood cell; WBC, white blood cell
Table 2. Changes in kidney biomarkers from BL at Wk 52 in the overall population (BEL, n=1869; PBO, n=1217) and among pts with BL proteinuria >0.5 g/24 hr (BEL, n=461; PBO, n=292)
*Logistic regression models were used to compare treatment groups for eGFR reductions and sCr increase with covariates for treatment group, study, BL eGFR/sCr value and BL SELENA SLEDAI score (≤9 vs ≥10). Analyses were not adjusted for multiplicity; †calculated based on last observation carried forward; ‡among pts who completed Wk 52 of the study. OR, odds ratio
Disclosures: M. Dall'Era, GlaxoSmithKline (GSK), AstraZeneca, Aurinia, BMS, Amgen; A. Fava, Sanofi; C. Henning, GlaxoSmithKline; A. Jones-Leone, GlaxoSmithKline (GSK); A. Carroll, GlaxoSmithKline (GSK); J. Harris, GlaxoSmithKline; A. Hammer, GlaxoSmithKline (GSK); R. Levy, GlaxoSmithKline (GSK); L. Magder, None; M. Petri, Exagen, AstraZeneca, Alexion, Amgen, AnaptysBio, Argenx, Aurinia, Biogen, Caribou Biosciences, CVS Health, EMD Serono, Eli Lilly, Emergent Biosolutions, GlaxoSmithKline (GSK), IQVIA, Janssen, Kira Pharmaceuticals, MedShr, Sanofi, SinoMab, Thermofisher, BPR Scientific Advisory Committee.
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