Abstract
Background:BLISS-LN (GSK Study BEL114054; NCT01639339), the largest lupus nephritis (LN) study to date, showed that intravenous (IV) belimumab (BEL) + standard therapy (ST) improved outcomes compared with ST alone in patients (pts) with active LN.1Objectives:To assess additional safety and efficacy data of BEL + ST in pts with LN in a 6-month open-label (OL) phase beyond 2 years of double-blind (DB) treatment in BLISS-LN.Methods:In this OL phase, eligible completers of the DB phase received monthly BEL 10 mg/kg IV + ST for 6 months. Endpoints: safety; Primary Efficacy Renal Response (PERR; uPCR ≤0.7; eGFR no worse than 20% below OL baseline eGFR or ≥60 ml/min/1.73 m2; no prohibited medications) and Complete Renal Response (CRR; uPCR <0.5; eGFR no worse than 10% below OL baseline eGFR or ≥90 ml/min/1.73 m2; no prohibited medications) at OL Week 28; proportion of pts with SLEDAI score <4; corticosteroid use; biomarkers. Analyses were based on observed data and summarised relative to the OL baseline (last value measured prior to the first dose of OL treatment).Results:We enrolled 257 pts (57.4% of pts in BEL114054) and treated 255 pts. All treated pts were included in the safety population (123 pts switched from placebo [PBO] to BEL; 132 pts remained on BEL). Efficacy was assessed in the safety population, excluding 1 pt due to non-compliance (mITT population; PBO to BEL: 122 pts; BEL to BEL: 132 pts). 96.5% of pts completed the OL phase; 3.5% withdrew, mainly due to adverse events (AE; 2.0%).Overall, 168/255 (65.9%) pts had ≥1 AE (76/123 [61.8%] PBO to BEL pts; 92/132 [69.7%] BEL to BEL pts); 15/255 (5.9%) pts had ≥1 serious AE (5/123 [4.1%] PBO to BEL pts; 10/132 [7.6%] BEL to BEL pts); 1 (0.8%) pt died in the PBO to BEL group.Proportions of PERR and CRR responders increased from OL baseline to OL Week 28 (Table 1. below)Proportions of pts who attained SLEDAI scores <4 increased from OL baseline to OL Week 28 in the BEL to BEL group and decreased in the PBO to BEL group. Among pts receiving average daily prednisone-equivalent doses of ≤5 mg or ≤7.5 mg dose was maintained from OL baseline to OL Week 28 (Table 1. below)In pts with autoantibodies at OL baseline, anti-dsDNA and anti-C1q levels decreased from OL baseline to OL Week 28 in both groups. Among pts with low C3/C4 levels at OL baseline, C3/C4 levels increased from OL baseline to OL Week 28 in both groups (Table 1. below)Conclusion:In this OL phase of BLISS-LN, proportions of PERR and CRR responders increased in both the BEL-naïve and BEL-experienced groups; and no new safety signals were observed. Improvements in biomarker levels were observed, especially in pts who switched from PBO to BEL.Funding:GSK.References:[1]Furie R, et al. N Engl J Med. 2020;383(12):1117-28.Table 1.Responses at OL baseline and OL Week 28 (mITT population, N=254)OL baseline*OL Week 28PBO to BEL(n=122)BEL to BEL(n=132)PBO to BEL(n=122)BEL to BEL(n=132)n122132118122PERR, n (%)73 (59.8)†93 (70.5)†79 (66.9)91 (74.6)CRR, n (%)44 (36.1)†63 (47.7)†57 (48.3)76 (62.3)SLEDAI score <4n122132120122Responders, n (%)44 (36.1)†64 (48.5)†40 (33.3)64 (52.5)Prednisone-equivalent dosen122132121128≤5 mg, n (%)59 (48.4)78 (59.1)60 (49.6)75 (58.6)≤7.5 mg, n (%)62 (50.8)85 (64.4)66 (54.5)83 (64.8)Anti-dsDNA (IU/ml)‡n85648161Median (IQR) levels107.0 (49.0, 212.0)65.5 (42.5, 126.5)--Median (IQR) % change from baseline---30.2 (-46.3, -6.8)-10.7 (-27.2, 9.1)Anti-C1q (U/ml)§n64605854Median (IQR) levels71.7 (36.6, 167.5)47.1 (33.0, 75.7)--Median (IQR) % change from baseline---23.0 (-41.5, 0.5)-16.5 (-33.0, 6.1)C3 (mg/dl)‖n45374435Median (IQR) levels78.0 (72.0, 83.0)80.0 (71.0, 84.0)--Median (IQR) % change from baseline--6.2 (-4.2, 14.6)4.7 (-4.8, 16.9)C4 (mg/dl)‖n18121811Median (IQR) levels7.5 (6.0, 8.0)7.0 (7.0, 8.5)--Median (IQR) % change from baseline--23.6 (11.1, 37.5)11.1 (0.0, 57.1)*DB Week 104 visit and the OL baseline visit were the same visit; †Post hoc analyses; ‡Among anti-dsDNA positive pts at OL baseline (≥30 IU/ml); §Among anti-C1q positive pts at OL baseline (≥22.2 U/ml); ‖Among pts with low C3 (<90 mg/dl)/C4 (<10 mg/dl) levels at OL baseline.Acknowledgements:Medical writing assistance was provided by Olga Conn, PhD, Fishawack Indicia Ltd., UK, part of Fishawack Health, and was funded by GSK.Disclosure of Interests:Richard Furie Consultant of: GSK, Grant/research support from: GSK, Brad H Rovin Consultant of: GSK, Frederic Houssiau Consultant of: GSK, Grant/research support from: UCB, Gabriel Contreras Consultant of: Genentech, Merck, Grant/research support from: Genentech, Merck, Paula Curtis Shareholder of: GSK, Employee of: GSK, Anuradha Madan Shareholder of: GSK, Employee of: GSK, Angela Jones-Leone Shareholder of: GSK, Employee of: GSK, Mohamed Okily Shareholder of: GSK, Employee of: GSK, David Roth Shareholder of: GSK, Employee of: GSK
