Op0164 bliss-Ln: A Randomised, Double-Blind, Placebo-Controlled Phase 3 Trial of Intravenous Belimumab in Patients With Active Lupus Nephritis

Abstract

Background:Lupus nephritis (LN), a serious manifestation of systemic lupus erythematosus (SLE), affects nearly 70% of patients (pts) in high-risk groups. To preserve renal function, LN requires fast and effective treatment. Despite medical advances, progression rates at 15 years to end-stage renal disease (ESRD) remain >40% for pts with diffuse proliferative LN. Belimumab (BEL), approved in pts aged ≥5 years with active SLE, improved renal parameters in pts with baseline renal involvement in apost hocanalysis of Phase 3 trials data.Objectives:To assess efficacy and safety of intravenous (IV) BEL vs placebo (PBO), plus standard therapy (ST), in pts with active LN.Methods:BLISS-LN is a Phase 3, randomised, double-blind, PBO-controlled, 104-week study (GSK Study BEL114054,NCT01639339). Adults with SLE and biopsy-proven LN (class III, IV, and/or V) were randomised (1:1) to monthly BEL 10 mg/kg IV or PBO, plus ST. Primary endpoint: Primary Efficacy Renal Response (PERR); defined as urine protein creatinine ratio [uPCR] ≤0.7; estimated glomerular filtration rate [eGFR] within 20% of the pre-flare value or ≥60 ml/min/1.73m2; no rescue therapy) at Week (Wk) 104. Key secondary endpoints: Complete Renal Response (CRR; defined as uPCR <0.5; eGFR within 10% of the pre-flare value or ≥90 ml/min/1.73m2; no rescue therapy) at Wk 104; PERR at Wk 52; time to renal-related event (defined as ESRD/doubling of serum creatinine/renal worsening/renal disease-related treatment failure) or death. Other endpoints: time to PERR/CRR sustained through Wk 104; SLEDAI-S2K score <4 points at Wk 104; safety.Results:Overall, 448 pts were randomised (efficacy: 223/group; safety: 224/group). Significantly more BEL (43%) than PBO (32.3%) pts achieved PERR at Wk 104 (OR 1.55, 95% CI 1.04, 2.32; p=0.0311). More BEL than PBO pts achieved key secondary and other efficacy endpoints (Table).Overall, 214 (95.5%) BEL and 211 (94.2%) PBO pts had ≥1 adverse event (AE); 58 (25.9%) BEL and 67 (29.9%) PBO pts had ≥1 serious AE; 29 (12.9%) pts in each group had ≥1 AE resulting in study treatment discontinuation; 4 (1.8%) BEL and 3 (1.3%) PBO pts developed on-treatment fatal AEs.Conclusion:In the largest LN study to date, data from BLISS-LN demonstrate that BEL plus ST significantly improves LN renal responses compared with ST alone with a favourable safety profile.Study funding: GSK.Table.Endpoint, n (%)PBO(n=223)BEL(n=223)OR/HR (95% CI) vs PBOp-valueCRR at Wk 104*44 (19.7)67 (30.0)OR 1.74(1.11, 2.74)0.0167PERR at Wk 52*79 (35.4)104 (46.6)OR 1.59(1.06, 2.38)0.0245Time to PERR throughWk 104†72 (32.3)96 (43.0)HR 1.46(1.07, 1.98)0.0157Time to CRR throughWk 104†44 (19.7)67 (30.0)HR 1.58(1.08, 2.31)0.0189Time to renal-related event or death†63 (28.3)35 (15.7)HR 0.51(0.34, 0.77)0.0014SLEDAI-S2K score <4 points at Wk 104*41 (18.4)62 (27.8)OR 1.76(1.11, 2.78)0.0164*PBO and BEL columns represent the n (%) responders†Data presented as n (cumulative incidence)Disclosure of Interests:Richard Furie Grant/research support from: GSK, Consultant of: GSK, Brad H Rovin Grant/research support from: GSK, Consultant of: GSK, Frederic Houssiau Grant/research support from: UCB, Consultant of: GSK, Zahir Amoura Grant/research support from: GSK, Roche, Consultant of: GSK, Astra Zeneca, Amgen, Mittermayer Santiago: None declared, Gabriel Contreras Grant/research support from: Genentech, Merck, Consultant of: Genentech, Merck, Ana Malvar Consultant of: GSK and Roche, chi chiu mok: None declared, Amit Saxena Consultant of: GSK, AZ, BMS, Xueqing Yu: None declared, Y.K. Onno Teng Grant/research support from: GSK, Consultant of: GSK, Aurinia Pharmaceuticals, Novartis, Carly Barnett Shareholder of: GSK, Employee of: GSK, Susan Burriss Shareholder of: GSK, Employee of: GSK, Yulia Green Shareholder of: GSK, Employee of: GSK, Beulah Ji Shareholder of: GSK, Employee of: GSK, Christi Kleoudis Shareholder of: GSK, Consultant of: GSK, Employee of: Parexel, David Roth Shareholder of: GSK, Employee of: GSK

Egyptian evidence-based consensus on clinical practice recommendations for the management of lupus nephritis

“…(2) Maintenance phase: which follows the induction phase and involves the continuation of immunosuppressive management. This phase aims at attaining a complete renal response and minimizing or preventing renal flares [46,47]. Sequential immunosuppressive treatments, such as cyclophosphamide followed by azathioprine, or monotherapy, such as MMF, can be used in both the induction and maintenance stages.…”

Anti-CD20 monoclonal antibodies in Systemic Lupus Erythematosus

“…Post marketing studies of Belimumab as well as registry data will provide further insights into real-life utility and its long-term safety profile. Abstract publication of BLISS-LN, a phase III trial of belimumab in patients with active LN demonstrated an 11% increased renal response rate when administering belimumab in addition to standard therapy compared to standard therapy alone (142). We await further studies of anti-BLyS treatment in African-American patients (143) and how other factors such as background therapy affect its outcomes.…”

The dawn of a new era of therapies in systemic lupus erythematosus

“…A recent phase III RCT (BLISS-LN) showed promise of belimumab in LN. [ 12 ] A total of 446 patients with biopsy-proven LN were randomized to receive either IV belimumab (10 mg/kg) or PBO in addition to SOC for induction therapy (74% mycophenolate mofetil (MMF); 26% cyclophosphamide (CYC)/azathioprine (AZA)). At Week 104, the primary outcome renal response (urine protein-to-creatinine ratio (uP/Cr) ≤0.7; estimated glomerular filtration rate (eGFR) ≤20% below pre-flare value or ≥60 mL/min/1.73 m 2 ; and no treatment failure) rate was significantly higher in the belimumab group compared with the than PBO group (43.0% vs. 32.3%; P = 0.03).…”