OBJECTIVE: To assess the efficacy/safety of the B lymphocyte stimulator inhibitor belimumab plus standard therapy compared with placebo plus standard therapy in active systemic lupus erythematosus (SLE). METHODS: In a phase III, multicenter, randomized, placebo-controlled trial, 819 antinuclear antibody-positive or anti-double-stranded DNA-positive SLE patients with scores ≥6 on the Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA) version of the SLE Disease Activity Index (SLEDAI) were randomized in a 1:1:1 ratio to receive 1 mg/kg belimumab, 10 mg/kg belimumab, or placebo intravenously on days 0, 14, and 28 and then every 28 days for 72 weeks. The primary efficacy end point was the SLE Responder Index (SRI) response rate at week 52 (an SRI response was defined as a ≥4-point reduction in SELENA-SLEDAI score, no new British Isles Lupus Assessment Group [BILAG] A organ domain score and no more than 1 new BILAG B score, and no worsening in physician's global assessment score versus baseline). RESULTS:Belimumab at 10 mg/kg plus standard therapy met the primary efficacy end point, generating a significantly greater SRI response at week 52 compared with placebo (43.2% versus 33.5%; P = 0.017). The rate with 1 mg/kg belimumab was 40.6% (P = 0.089). Response rates at week 76 were 32.4%, 39.1%, and 38.5% with placebo, 1 mg/kg belimumab, and 10 mg/kg belimumab, respectively. In post hoc sensitivity analyses evaluating higher SELENA-SLEDAI score thresholds, 10 mg/kg belimumab achieved better discrimination at weeks 52 and 76. Risk of severe flares over 76 weeks (based on the modified SLE Flare Index) was reduced with 1 mg/kg belimumab (34%) (P = 0.023) and 10 mg/kg belimumab (23%) (P = 0.13). Serious and severe adverse events, including infections, laboratory abnormalities, malignancies, and deaths, were comparable across groups. CONCLUSION:Belimumab plus standard therapy significantly improved SRI response rate, reduced SLE disease activity and severe flares, and was generally well tolerated in SLE.
RCT Entities:
OBJECTIVE: To assess the efficacy/safety of the B lymphocyte stimulator inhibitor belimumab plus standard therapy compared with placebo plus standard therapy in active systemic lupus erythematosus (SLE). METHODS: In a phase III, multicenter, randomized, placebo-controlled trial, 819 antinuclear antibody-positive or anti-double-stranded DNA-positive SLEpatients with scores ≥6 on the Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA) version of the SLE Disease Activity Index (SLEDAI) were randomized in a 1:1:1 ratio to receive 1 mg/kg belimumab, 10 mg/kg belimumab, or placebo intravenously on days 0, 14, and 28 and then every 28 days for 72 weeks. The primary efficacy end point was the SLE Responder Index (SRI) response rate at week 52 (an SRI response was defined as a ≥4-point reduction in SELENA-SLEDAI score, no new British Isles Lupus Assessment Group [BILAG] A organ domain score and no more than 1 new BILAG B score, and no worsening in physician's global assessment score versus baseline). RESULTS:Belimumab at 10 mg/kg plus standard therapy met the primary efficacy end point, generating a significantly greater SRI response at week 52 compared with placebo (43.2% versus 33.5%; P = 0.017). The rate with 1 mg/kg belimumab was 40.6% (P = 0.089). Response rates at week 76 were 32.4%, 39.1%, and 38.5% with placebo, 1 mg/kg belimumab, and 10 mg/kg belimumab, respectively. In post hoc sensitivity analyses evaluating higher SELENA-SLEDAI score thresholds, 10 mg/kg belimumab achieved better discrimination at weeks 52 and 76. Risk of severe flares over 76 weeks (based on the modified SLE Flare Index) was reduced with 1 mg/kg belimumab (34%) (P = 0.023) and 10 mg/kg belimumab (23%) (P = 0.13). Serious and severe adverse events, including infections, laboratory abnormalities, malignancies, and deaths, were comparable across groups. CONCLUSION:Belimumab plus standard therapy significantly improved SRI response rate, reduced SLE disease activity and severe flares, and was generally well tolerated in SLE.
Authors: Sandra V Navarra; Renato M Guzmán; Alberto E Gallacher; Stephen Hall; Roger A Levy; Renato E Jimenez; Edmund K-M Li; Mathew Thomas; Ho-Youn Kim; Manuel G León; Coman Tanasescu; Eugeny Nasonov; Joung-Liang Lan; Lilia Pineda; Z John Zhong; William Freimuth; Michelle A Petri Journal: Lancet Date: 2011-02-04 Impact factor: 79.321
Authors: Michelle Petri; Mimi Y Kim; Kenneth C Kalunian; Jennifer Grossman; Bevra H Hahn; Lisa R Sammaritano; Michael Lockshin; Joan T Merrill; H Michael Belmont; Anca D Askanase; W Joseph McCune; Michelene Hearth-Holmes; Mary Anne Dooley; Joan Von Feldt; Alan Friedman; Mark Tan; John Davis; Mary Cronin; Betty Diamond; Meggan Mackay; Lisa Sigler; Michael Fillius; Ann Rupel; Frederick Licciardi; Jill P Buyon Journal: N Engl J Med Date: 2005-12-15 Impact factor: 91.245
Authors: Michelle Petri; William Stohl; Winn Chatham; W Joseph McCune; Marc Chevrier; Jeff Ryel; Virginia Recta; John Zhong; William Freimuth Journal: Arthritis Rheum Date: 2008-08
Authors: William Stohl; Falk Hiepe; Kevin M Latinis; Mathew Thomas; Morton A Scheinberg; Ann Clarke; Cynthia Aranow; Frank R Wellborne; Carlos Abud-Mendoza; Douglas R Hough; Lilia Pineda; Thi-Sau Migone; Z John Zhong; William W Freimuth; W Winn Chatham Journal: Arthritis Rheum Date: 2012-07