A phase III, randomized, placebo-controlled study of belimumab, a monoclonal antibody that inhibits B lymphocyte stimulator, in patients with systemic lupus erythematosus
Richard Furie,Michelle A. Petri,Omid Zamani,Ricard Cervera,Daniel J. Wallace,D. Tegzova,Jorge Sanchez-Guerrero,Andreas Schwarting,Joan T. Merrill,W. Winn Chatham,William Stohl,Ellen M. Ginzler,Douglas R. Hough,Z. John Zhong,William W. Freimuth,Ronald F van Vollenhoven +15 more
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Belimumab plus standard therapy significantly improved SRI response rate, reduced SLE disease activity and severe flares, and was generally well tolerated in SLE.Abstract:
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 (432% versus 335%; P = 0017) The rate with 1 mg/kg belimumab was 406% (P = 0089) Response rates at week 76 were 324%, 391%, and 385% 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 = 0023) and 10 mg/kg belimumab (23%) (P = 013) 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 SLEread more
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American College of Rheumatology guidelines for screening, treatment, and management of lupus nephritis
Bevra H. Hahn,Maureen McMahon,Alan H. Wilkinson,W. Dean Wallace,David I. Daikh,John FitzGerald,George Karpouzas,Joan T. Merrill,Daniel J. Wallace,Jinoos Yazdany,Rosalind Ramsey-Goldman,Karandeep Singh,Mazdak A. Khalighi,Soo I. Choi,Maneesh Gogia,Suzanne Kafaja,Mohammad Kamgar,Christine Lau,William J. Martin,Sefali Parikh,Justin Peng,Anjay Rastogi,Weiling Chen,Jennifer M. Grossman +23 more
TL;DR: The management strategies discussed here apply to lupus nephritis in adults, particularly to those receiving care in the United States of America, and include interventions that were available in theUnited States as of April 2011.
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2019 update of the EULAR recommendations for the management of systemic lupus erythematosus
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TL;DR: The updated recommendations provide physicians and patients with updated consensus guidance on the management of SLE, combining evidence-base and expert-opinion, based on emerging new evidence.
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Systemic lupus erythematosus.
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Trial of Anifrolumab in Active Systemic Lupus Erythematosus
Eric F Morand,Richard Furie,Yoshiya Tanaka,Ian N. Bruce,Anca Askanase,Christophe Richez,Sang Cheol Bae,Philip Z Brohawn,Lilia Pineda,Anna Berglind,Raj Tummala,Tulip Trial Investigators +11 more
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References
More filters
Book
SF-36 health survey: Manual and interpretation guide
TL;DR: TheSF-36 is a generic health status measure which has gained popularity as a measure of outcome in a wide variety of patient groups and social and the contribution of baseline health, sociodemographic and work-related factors to the SF-36 Health Survey: manual and interpretation guide is tested.
Journal ArticleDOI
Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus.
TL;DR: In 1992, Piette and colleagues suggested that the ACR revised criteria be reevaluated in light of the above discoveries, and the presence and clinical associations or antiphospholipid antibodies in patients with SLE was suggested.
Journal ArticleDOI
Efficacy and safety of belimumab in patients with active systemic lupus erythematosus: a randomised, placebo-controlled, phase 3 trial
Sandra V. Navarra,Renato Guzman,Alberto E. Gallacher,Stephen B. Hall,Roger A. Levy,Renato E. Jimenez,Edmund K. Li,Mathew Thomas,Ho-Youn Kim,Manuel G. León,Coman Tanasescu,Eugeny L. Nasonov,Joung-Liang Lan,Lilia Pineda,Z. John Zhong,William W. Freimuth,Michelle A. Petri +16 more
TL;DR: The efficacy and safety of the fully human monoclonal antibody belimumab (BLyS-specific inhibitor) was assessed in patients with active systemic lupus erythematosus in a multicentre phase 3 study done in Latin America, Asia-Pacific, and eastern Europe.
Journal ArticleDOI
BLyS: Member of the Tumor Necrosis Factor Family and B Lymphocyte Stimulator
Paul A. Moore,Ornella Belvedere,Amy Orr,Krystyna Pieri,David W. Lafleur,Ping Feng,Daniel R. Soppet,Meghan Charters,Reiner L. Gentz,David Parmelee,Yuling Li,Olga Galperina,Judith Giri,Viktor Roschke,Bernardetta Nardelli,Jeffrey Carrell,Svetlana Sosnovtseva,Wilbert Greenfield,Steven M. Ruben,Henrik S. Olsen,James Fikes,David M. Hilbert +21 more
TL;DR: The biological profile of BLyS suggests it is involved in monocyte-driven B cell activation, and its expression on human monocytes could be up-regulated by interferon-gamma.
Journal ArticleDOI
Mortality in systemic lupus erythematosus.
Sasha Bernatsky,J. F. Boivin,Lawrence Joseph,S. Manzi,Ellen M. Ginzler,Dafna D. Gladman,Murray B. Urowitz,Paul R. Fortin,M. Petri,Susan G. Barr,Caroline Gordon,Sang Cheol Bae,David A. Isenberg,Asad Zoma,Cynthia Aranow,Mary Anne Dooley,Ola Nived,Gunnar Sturfelt,Kristjan Steinsson,Graciela S. Alarcón,J L Senécal,Michel Zummer,John G. Hanly,Stephanie Ensworth,Janet E. Pope,Steven M. Edworthy,Anisur Rahman,J Sibley,Hani El-Gabalawy,Timothy McCarthy,Y. St. Pierre,Ann E. Clarke,Rosalind Ramsey-Goldman +32 more
TL;DR: The Lupus Survival Study Group data are reviewed and particularly the data from the State University of New York Health Science Center at Brooklyn, NY is reviewed.