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Robin P Choudhury, Jacqueline S Birks, Venkatesh Mani, Luca Biasiolli, Matthew D Robson, Philippe L L'Allier, Marc-Alexandre Gingras, Nadia Alie, Mary Ann McLaughlin, Craig T Basson, Alison D Schecter, Eric C Svensson, Yiming Zhang, Denise Yates, Jean-Claude Tardif, Zahi A Fayad
BACKGROUND: Evidence suggests that interleukin (IL)-1β is important in the pathogenesis of atherosclerosis and its complications and that inhibiting IL-1β may favorably affect vascular disease progression. OBJECTIVES: The goal of this study was to evaluate the effects of IL-1β inhibition with canakinumab versus placebo on arterial structure and function, determined by magnetic resonance imaging. METHODS: Patients (N = 189) with atherosclerotic disease and either type 2 diabetes mellitus or impaired glucose tolerance were randomized to receive placebo (n = 94) or canakinumab 150 mg monthly (n = 95) for 12 months...
October 18, 2016: Journal of the American College of Cardiology
Tianhe Li, Liming Xu, Guiping Ren, Chengkai Yin, Bing Zhou, Xianlong Ye, Qingcui Li, Ning Li, Deshan Li
OBJECTIVE: RA is one of autoimmune diseases, has drawn great attention of the world. Currently, the anti- IL-1β monoclonal antibody Canakinumab (ACZ885) for treatment of RA has entered into clinical trials. However, Full length antibody has large molecular weight, and is difficult to penetrate the tissue or the nidus. In contrast, scFv has low molecular weight and strong penetration ability, and is favorable to increase the drug concentration in the indus, hence improving the efficacy of the drug...
2013: Current Pharmaceutical Biotechnology
Jasmin B Kuemmerle-Deschner, Eduardo Ramos, Norbert Blank, Joachim Roesler, Sandra D Felix, Thomas Jung, Kirstin Stricker, Abhijit Chakraborty, Stacey Tannenbaum, Andrew M Wright, Christiane Rordorf
INTRODUCTION: Cryopyrin-associated periodic syndrome (CAPS) represents a spectrum of three auto-inflammatory syndromes, familial cold auto-inflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS), and neonatal-onset multisystem inflammatory disease/chronic infantile neurological cutaneous and articular syndrome (NOMID/CINCA) with etiology linked to mutations in the NLRP3 gene resulting in elevated interleukin-1β (IL-1β) release. CAPS is a rare hereditary auto-inflammatory disease, which may start early in childhood and requires a life-long treatment...
2011: Arthritis Research & Therapy
Eugen Dhimolea
Canakinumab (ACZ885, Ilaris) is a human anti-IL-1beta monoclonal antibody developed by Novartis. Its mode of action is based on the neutralization of IL-1beta signaling, resulting in suppression of inflammation in patients with disorders of autoimmune origin. In June 2009 the drug was approved by the US Food and Drug Administration for the treatment of familial cold auto-inflammatory syndrome and Muckle-Wells syndrome, which are inflammatory diseases related to cryopyrin-associated periodic syndromes. The drug is currently being evaluated for its potential in the treatment of rheumatoid arthritis, systemic-onset juvenile idiopathic arthritis, chronic obstructive pulmonary disease, type 1 and 2 diabetes and ocular diseases...
January 2010: MAbs
Helen J Lachmann, Philip Lowe, Sandra Daniela Felix, Christiane Rordorf, Kieron Leslie, Sheril Madhoo, Helmut Wittkowski, Stephan Bek, Nicole Hartmann, Sophie Bosset, Philip N Hawkins, Thomas Jung
The investigation of interleukin 1beta (IL-1beta) in human inflammatory diseases is hampered by the fact that it is virtually undetectable in human plasma. We demonstrate that by administering the anti-human IL-1beta antibody canakinumab (ACZ885) to humans, the resulting formation of IL-1beta-antibody complexes allowed the detection of in vivo-produced IL-1beta. A two-compartment mathematical model was generated that predicted a constitutive production rate of 6 ng/d IL-1beta in healthy subjects. In contrast, patients with cryopyrin-associated periodic syndromes (CAPS), a rare monogenetic disease driven by uncontrolled caspase-1 activity and IL-1 production, produced a mean of 31 ng/d...
May 11, 2009: Journal of Experimental Medicine
Rieke Alten, Hermann Gram, Leo A Joosten, Wim B van den Berg, Joachim Sieper, Siegfrid Wassenberg, Gerd Burmester, Piet van Riel, Maria Diaz-Lorente, Gerardus J M Bruin, Thasia G Woodworth, Christiane Rordorf, Yannik Batard, Andrew M Wright, Thomas Jung
INTRODUCTION: IL-1beta is a proinflammatory cytokine driving joint inflammation as well as systemic signs of inflammation, such as fever and acute phase protein production. METHODS: ACZ885, a fully human monoclonal antibody that neutralizes the bioactivity of human IL-1beta, was generated to study the potent and long-lasting neutralization of IL-1beta in mechanistic animal models as well as in a proof-of-concept study in patients with rheumatoid arthritis (RA). RESULTS: The mouse IL-1 receptor cross-reacts with human IL-1beta, and it was demonstrated that ACZ885 can completely suppress IL-1beta-mediated joint inflammation and cartilage destruction in mice...
2008: Arthritis Research & Therapy
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