Richard Furie1, Brad H Rovin1, Frédéric Houssiau1, Ana Malvar1, Y K Onno Teng1, Gabriel Contreras1, Zahir Amoura1, Xueqing Yu1, Chi-Chiu Mok1, Mittermayer B Santiago1, Amit Saxena1, Yulia Green1, Beulah Ji1, Christi Kleoudis1, Susan W Burriss1, Carly Barnett1, David A Roth1. 1. From the Division of Rheumatology, Northwell Health, Donald and Barbara Zucker School of Medicine at Hofstra-Northwell, Great Neck, NY (R.F.); the Division of Nephrology, Ohio State University, Columbus (B.H.R.); Pôle de Pathologies Rhumatismales Inflammatoires et Systémiques, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, and Service de Rhumatologie, Cliniques Universitaires Saint-Luc - both in Brussels (F.H.); Organización Médica de Investigación, Buenos Aires (A.M.); the Department of Internal Medicine, Section of Nephrology, Leiden University Medical Center, Leiden, the Netherlands (Y.K.O.T.); the Division of Nephrology, Division of Hypertension, Department of Medicine, University of Miami Miller School of Medicine, Miami (G.C.); Sorbonne Université, INSERM Unité 1135 (Z.A.), and Assistance Publique-Hôpitaux de Paris Sorbonne Université, Service de Médecine Interne 2, Institut Endocrinologie, Maladies Métaboliques et Médecine Interne, Centre de Référence National du Lupus et Syndrome des Antiphospholipides, Hôpital Pitié-Salpêtrière (Z.A.) - both in Paris; the Department of Nephrology, Guangdong Provincial People's Hospital and Guangdong Academy of Medical Sciences, Guangzhou (X.Y.), and the Department of Medicine, Tuen Mun Hospital, Hong Kong (C.C.M.) - both in China; Escola Bahiana de Medicina e Saúde Pública, Salvador, Brazil (M.B.S.); the Division of Rheumatology, New York University School of Medicine, New York (A.S.); GlaxoSmithKline, Stockley Park, Uxbridge, United Kingdom (Y.G., B.J.); Parexel, Durham, NC (C.K.); and GlaxoSmithKline, Collegeville, PA (S.W.B., C.B., D.A.R.).
Abstract
BACKGROUND: In adults with active lupus nephritis, the efficacy and safety of intravenous belimumab as compared with placebo, when added to standard therapy (mycophenolate mofetil or cyclophosphamide-azathioprine), are unknown. METHODS: In a phase 3, multinational, multicenter, randomized, double-blind, placebo-controlled, 104-week trial conducted at 107 sites in 21 countries, we assigned adults with biopsy-proven, active lupus nephritis in a 1:1 ratio to receiveintravenous belimumab (at a dose of 10 mg per kilogram of body weight) or matching placebo, in addition to standard therapy. The primary end point at week 104 was a primary efficacy renal response (a ratio of urinary protein to creatinine of ≤0.7, an estimated glomerular filtration rate [eGFR] that was no worse than 20% below the value before the renal flare (pre-flare value) or ≥60 ml per minute per 1.73 m2 of body-surface area, and no use of rescue therapy), and the major secondary end point was a complete renal response (a ratio of urinary protein to creatinine of <0.5, an eGFR that was no worse than 10% below the pre-flare value or ≥90 ml per minute per 1.73 m2, and no use of rescue therapy). The time to a renal-related event or death was assessed. RESULTS: A total of 448 patients underwent randomization (224 to the belimumab group and 224 to the placebo group). At week 104, significantly more patients in the belimumab group than in the placebo group had a primary efficacy renal response (43% vs. 32%; odds ratio, 1.6; 95% confidence interval [CI], 1.0 to 2.3; P = 0.03) and a complete renal response (30% vs. 20%; odds ratio, 1.7; 95% CI, 1.1 to 2.7; P = 0.02). The risk of a renal-related event or death was lower among patients who received belimumab than among those who received placebo (hazard ratio, 0.51; 95% CI, 0.34 to 0.77; P = 0.001). The safety profile of belimumab was consistent with that in previous trials. CONCLUSIONS: In this trial involving patients with active lupus nephritis, more patients who received belimumab plus standard therapy had a primary efficacy renal response than those who received standard therapy alone. (Funded by GlaxoSmithKline; BLISS-LN ClinicalTrials.gov number, NCT01639339.).
RCT Entities:
BACKGROUND: In adults with active lupus nephritis, the efficacy and safety of intravenous belimumab as compared with placebo, when added to standard therapy (mycophenolate mofetil or cyclophosphamide-azathioprine), are unknown. METHODS: In a phase 3, multinational, multicenter, randomized, double-blind, placebo-controlled, 104-week trial conducted at 107 sites in 21 countries, we assigned adults with biopsy-proven, active lupus nephritis in a 1:1 ratio to receive intravenous belimumab (at a dose of 10 mg per kilogram of body weight) or matching placebo, in addition to standard therapy. The primary end point at week 104 was a primary efficacy renal response (a ratio of urinary protein to creatinine of ≤0.7, an estimated glomerular filtration rate [eGFR] that was no worse than 20% below the value before the renal flare (pre-flare value) or ≥60 ml per minute per 1.73 m2 of body-surface area, and no use of rescue therapy), and the major secondary end point was a complete renal response (a ratio of urinary protein to creatinine of <0.5, an eGFR that was no worse than 10% below the pre-flare value or ≥90 ml per minute per 1.73 m2, and no use of rescue therapy). The time to a renal-related event or death was assessed. RESULTS: A total of 448 patients underwent randomization (224 to the belimumab group and 224 to the placebo group). At week 104, significantly more patients in the belimumab group than in the placebo group had a primary efficacy renal response (43% vs. 32%; odds ratio, 1.6; 95% confidence interval [CI], 1.0 to 2.3; P = 0.03) and a complete renal response (30% vs. 20%; odds ratio, 1.7; 95% CI, 1.1 to 2.7; P = 0.02). The risk of a renal-related event or death was lower among patients who received belimumab than among those who received placebo (hazard ratio, 0.51; 95% CI, 0.34 to 0.77; P = 0.001). The safety profile of belimumab was consistent with that in previous trials. CONCLUSIONS: In this trial involving patients with active lupus nephritis, more patients who received belimumab plus standard therapy had a primary efficacy renal response than those who received standard therapy alone. (Funded by GlaxoSmithKline; BLISS-LN ClinicalTrials.gov number, NCT01639339.).