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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. 1
Objectives: 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 m 2 ; 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 m 2 ; 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.
Responses at OL baseline and OL Week 28 (mITT population, N=254)
| OL baseline* | OL Week 28 | |||
|
PBO to BEL
|
BEL to BEL
|
PBO to BEL
|
BEL to BEL
|
|
| n | 122 | 132 | 118 | 122 |
| PERR, 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 <4 | ||||
| n | 122 | 132 | 120 | 122 |
| Responders, n (% ) | 44 (36.1) † | 64 (48.5) † | 40 (33.3) | 64 (52.5) |
| Prednisone-equivalent dose | ||||
| n | 122 | 132 | 121 | 128 |
| ≤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 ) ‡ | ||||
| n | 85 | 64 | 81 | 61 |
| Median (IQR) levels | 107.0 (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 ) § | ||||
| n | 64 | 60 | 58 | 54 |
| Median (IQR) levels | 71.7 (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 ) ‖ | ||||
| n | 45 | 37 | 44 | 35 |
| Median (IQR) levels | 78.0 (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 ) ‖ | ||||
| n | 18 | 12 | 18 | 11 |
| Median (IQR) levels | 7.5 (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