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Canakinumab

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https://www.readbyqxmd.com/read/29146124/relationship-of-c-reactive-protein-reduction-to-cardiovascular-event-reduction-following-treatment-with-canakinumab-a-secondary-analysis-from-the-cantos-randomised-controlled-trial
#1
Paul M Ridker, Jean G MacFadyen, Brendan M Everett, Peter Libby, Tom Thuren, Robert J Glynn
BACKGROUND: Canakinumab, a monoclonal antibody targeting interleukin-1β, reduces inflammation and cardiovascular event rates with no effect on lipid concentrations. However, it is uncertain which patient groups benefit the most from treatment and whether reductions in the inflammatory biomarker high-sensitivity C-reactive protein (hsCRP) correlate with clinical benefits for individual patients. METHODS: The Canakinumab Anti-Inflammatory Thrombosis Outcomes Study (CANTOS) used computer-generated codes to randomly allocate 10 061 men and women with a history of myocardial infarction to placebo or one of three doses of canakinumab (50 mg, 150 mg, or 300 mg) given subcutaneously once every 3 months...
November 13, 2017: Lancet
https://www.readbyqxmd.com/read/29111302/-cryopyrin-associated-periodic-syndromes
#2
P Quartier, F Rodrigues, S Georgin-Lavialle
Cryopyrin-associated periodic syndromes (CAPS) are linked to one single gene mutations, however they are associated with 3 syndromes, which are, from the mildest to the most severe phenotype familial cold urticaria, Muckle-Wells syndrome and chronic, infantile, neurologic, cutaneous, articular (CINCA) syndrome also called neonatal-onset multisystem inflammatory disease (NOMID). Autosomic dominant inheritance is present in most cases but in CINCA/NOMID syndrome where neomutations are more common. Mutations in the gene encoding cryopyrin, NLRP3, are associated with deregulation of caspase-1 activity, excessive interleukin-1 production and an autoinflammatory syndrome, which in familial cold urticaria and Muckle-Wells syndrome may be triggered or worsened by exposure to coldness...
October 27, 2017: La Revue de Médecine Interne
https://www.readbyqxmd.com/read/29110911/blau-syndrome-with-good-reponses-to-tocilizumab-a-case-report-and-focused-literature-review
#3
Li Lu, Min Shen, Dongbin Jiang, Yanmin Li, Xiaolong Zheng, Yao Li, Zhixun Li, Leilei Zhang, Jungen Tang, Yanke Guo, Shengyun Liu, Zhaohui Zheng, Guanmin Gao, Quancheng Kan
OBJECTIVES: Blau syndrome (BS), a rare auto-inflammatory granulomatous disease, is a progressive disorder. Usually the maintenance dose of glucocorticoid may not be tapered below 15 mg per day while immunosuppressives is used. There has been some experience with biologic agents in refractory BS patients. The objective of this study is to describe the case of a BS patient benefiting from Tocilizumab, a humanized monoclonal antibody against interleukin 6 receptor. METHODS: We report the first Chinese patient with BS who was resistant to currently available therapies but had rapid quiescence after using Tocilizumab...
September 25, 2017: Seminars in Arthritis and Rheumatism
https://www.readbyqxmd.com/read/29093432/european-society-of-cardiology-esc-annual-congress-report-from-barcelona-2017
#4
Kimio Satoh, Jun Takahashi, Yasuharu Matsumoto, Shunsuke Tatebe, Tatsuo Aoki, Yoku Kikuchi, Kiyotaka Hao, Kazuma Ohyama, Masamichi Nogi, Akira Suda, Shintaro Kasahara, Koichi Sato, Sadamitsu Ichijo, Hiroaki Shimokawa
From August 26th to 30th, the 2017 Annual Congress of the European Society of Cardiology (ESC 2017) was held in Barcelona, Spain. Despite the terrorism tradegy just before the ESC congress, the congress attracted many medical professionals from all over the world to discuss the recent topics in cardiovascular medicine in more than 500 sessions, including COMPASS (Cardiovascular OutcoMes for People using Anticoagulation StrategieS Trial), CANTOS (Canakinumab Anti-Inflammatory Thrombosis Outcomes Study), and ORION (which assessed the effect of a novel siRNA inhibitor to PCSK9 on reductions in low-density lipoprotein cholesterol)...
November 2, 2017: Circulation Journal: Official Journal of the Japanese Circulation Society
https://www.readbyqxmd.com/read/29045288/effects-of-anti-inflammatory-medications-in-patients-with-coronary-artery-disease-a-focus-on-losmapimod
#5
Bradley Tun, William H Frishman
Inflammation plays an integral role in atherogenesis and the pathogenesis of coronary artery disease (CAD). The question remains as to whether targeted inhibition of specific pathways of inflammation will have any clinical benefits in CAD. In this article we will review p38 mitogen-activated protein kinase (p38 MAPK), one of the key sensors of cellular stress that plays an important role in the inflammatory cascade. In addition, we will review losmapimod, a reversible competitive inhibitor of the α and β isoforms of p38 MAPK, and its efficacy when added to standard of care in patients hospitalized with myocardial infarction...
October 17, 2017: Cardiology in Review
https://www.readbyqxmd.com/read/28992387/a-nationwide-experience-with-the-off-label-use-of-interleukin-1-targeting-treatment-in-familial-mediterranean-fever-patients
#6
Servet Akar, Pınar Cetin, Umut Kalyoncu, Omer Karadag, Ismail Sari, Muhammed Cınar, Sedat Yilmaz, Ahmet Mesut Onat, Bunyamin Kisacik, Abdulsamet Erten, Ayse Balkarli, Orhan Kucuksahin, Sibel Yilmaz Oner, Soner Senel, Abdurrahman Tufan, Haner Direskeneli, Ferhat Oksuz, Yavuz Pehlivan, Ozun Bayindir, Gokhan Keser, Kenan Aksu, Ahmet Omma, Timucin Kasifoglu, Ali Ugur Unal, Fatih Yildiz, Mehmet Ali Balci, Sule Yavuz, Sukran Erten, Metin Ozgen, Mehmet Sayarlıoglu, Atalay Dogru, Gozde Yildirim, Fatma Alibaz Oner, Mehmet Engin Tezcan, Omer Nuri Pamuk, Fatos Onen
OBJECTIVE: Around 30-45% of patients with familial Mediterranean fever (FMF) have been reported to have attacks despite colchicine treatment. Currently, data on the treatment of colchicine-unresponsive or colchicine-intolerant FMF patients are limited; the most promising alternatives seem to be anti-interleukin-1 (anit-IL1) agents. Herein we report our experience with the off-label use of anti-IL1 agents in a large group of FMF patients. METHODS: In all, 21 centers from different geographical regions of Turkey were included in the current study...
October 9, 2017: Arthritis Care & Research
https://www.readbyqxmd.com/read/28980900/one-year-in-review-2017-beh%C3%A3-et-s-syndrome
#7
REVIEW
Gulen Hatemi, Emire Seyahi, Izzet Fresko, Rosaria Talarico, Vedat Hamuryudan
A meta-analysis showed that methodological differences in prevalence studies such as a sample survey design or census design may be responsible for some of the variance in BS prevalence reported across countries, in addition to a true geographic variation. Efforts towards developing a data driven core set of outcome measures for clinical trials is continuing. Multimodal imaging using color fundus photography, fluorescein angiography, and optical coherence tomography is essential in visualising diagnostic features, detecting structural changes, and monitoring disease activity and response to treatment in Behçet's uveitis...
September 29, 2017: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/28968868/international-multi-centre-study-of-pregnancy-outcomes-with-interleukin-1-inhibitors
#8
Taryn Youngstein, Patrycja Hoffmann, Ahmet Gül, Thirusha Lane, Rene Williams, Dorota M Rowczenio, Huri Ozdogan, Serdal Ugurlu, John Ryan, Len Harty, Sean Riminton, Alex P Headley, Joachim Roesler, Norbert Blank, Jasmin B Kuemmerle-Deschner, Anna Simon, Adrian S Woolf, Philip N Hawkins, Helen J Lachmann
Objective: To provide outcome data concerning pregnancies exposed to the Interleukin-1 (IL-1) inhibitors prior to conception in both men and women, during pregnancy and breast feeding. Methods: Retrospective data were collected from members of the International Society for Systemic Autoinflammatory diseases and collated in a single centre. A uniform data collection sheet was used to obtain standardized data including maternal age and diagnosis, type, duration of and response to IL-1 blockade, pregnancy duration, delivery, mode of feeding and neonatal development...
August 23, 2017: Rheumatology
https://www.readbyqxmd.com/read/28855077/effect-of-interleukin-1%C3%AE-inhibition-with-canakinumab-on-incident-lung-cancer-in-patients-with-atherosclerosis-exploratory-results-from-a-randomised-double-blind-placebo-controlled-trial
#9
Paul M Ridker, Jean G MacFadyen, Tom Thuren, Brendan M Everett, Peter Libby, Robert J Glynn
BACKGROUND: Inflammation in the tumour microenvironment mediated by interleukin 1β is hypothesised to have a major role in cancer invasiveness, progression, and metastases. We did an additional analysis in the Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS), a randomised trial of the role of interleukin-1β inhibition in atherosclerosis, with the aim of establishing whether inhibition of a major product of the Nod-like receptor protein 3 (NLRP3) inflammasome with canakinumab might alter cancer incidence...
August 25, 2017: Lancet
https://www.readbyqxmd.com/read/28854317/canakinumab-for-severe-hidradenitis-suppurativa-preliminary-experience-in-2-cases
#10
Carine Houriet, S Morteza Seyed Jafari, Rahel Thomi, Christoph Schlapbach, Luca Borradori, Nikhil Yawalkar, Robert E Hunger
No abstract text is available yet for this article.
November 1, 2017: JAMA Dermatology
https://www.readbyqxmd.com/read/28845751/antiinflammatory-therapy-with-canakinumab-for-atherosclerotic-disease
#11
RANDOMIZED CONTROLLED TRIAL
Paul M Ridker, Brendan M Everett, Tom Thuren, Jean G MacFadyen, William H Chang, Christie Ballantyne, Francisco Fonseca, Jose Nicolau, Wolfgang Koenig, Stefan D Anker, John J P Kastelein, Jan H Cornel, Prem Pais, Daniel Pella, Jacques Genest, Renata Cifkova, Alberto Lorenzatti, Tamas Forster, Zhanna Kobalava, Luminita Vida-Simiti, Marcus Flather, Hiroaki Shimokawa, Hisao Ogawa, Mikael Dellborg, Paulo R F Rossi, Roland P T Troquay, Peter Libby, Robert J Glynn
BACKGROUND: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. METHODS: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter...
September 21, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28798075/cytokines-of-the-il-1-family-recognized-targets-in-chronic-inflammation-underrated-in-organ-transplantations
#12
REVIEW
Ilja Striz
Interleukin 1 (IL-1) family is a group of cytokines with multiple local and systemic effects, which regulates both innate and adaptive immune responses. Generally, most IL-1 family cytokines express prevailing pro-inflammatory activities (IL-1α, IL-1β, IL-18, IL-33, IL-36 α, β, γ), whereas others are anti-inflammatory (IL-1Ra (IL-1 receptor antagonist), IL-36Ra, IL-38, IL-37). In addition to their immunomodulatory roles, some of them are also involved in the physiological modulation of homeostatic processes and directly affect mRNA transcription...
September 1, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28757235/adult-onset-still-s-disease-the-evidence-that-anti-interleukin-1-treatment-is-effective-and-well-tolerated-a-comprehensive-literature-review
#13
REVIEW
Guido Junge, June Mason, Eugen Feist
The literature contains many reports of the use of commercially available anti-IL-1 agents (anakinra/Kineret(®), canakinumab/Ilaris(®), or rilonacept/Arcalyst(®)) in treatment-resistant adult-onset Still's disease (AOSD). These have been widely summarized in many review articles, but a full account of all reports with each of the agents used is not available. This literature review includes all reports of treatment outcomes in patients treated for AOSD with any commercially available anti-IL-1 agent (excluding cases of unconfirmed or atypical AOSD or treatments only for rare AOSD complications)...
June 23, 2017: Seminars in Arthritis and Rheumatism
https://www.readbyqxmd.com/read/28659802/response-to-interleukin-1-inhibitors-in-140-italian-patients-with-adult-onset-still-s-disease-a-multicentre-retrospective-observational-study
#14
Serena Colafrancesco, Roberta Priori, Guido Valesini, Lorenza Argolini, Elena Baldissera, Elena Bartoloni, Daniele Cammelli, Giovanni Canestrari, Luca Cantarini, Elena Cavallaro, Giulio Cavalli, Lucia Cerrito, Paola Cipriani, Lorenzo Dagna, Ginevra De Marchi, Salvatore De Vita, Giacomo Emmi, Gianfranco Ferraccioli, Micol Frassi, Mauro Galeazzi, Roberto Gerli, Roberto Giacomelli, Elisa Gremese, Florenzo Iannone, Giovanni Lapadula, Giuseppe Lopalco, Raffaele Manna, Alessandro Mathieu, Carlomaurizio Montecucco, Marta Mosca, Ilaria Piazza, Matteo Piga, Irene Pontikaki, Micol Romano, Silvia Rossi, Maurizio Rossini, Piero Ruscitti, Elena Silvestri, Chiara Stagnaro, Rosaria Talarico, Angela Tincani, Ombretta Viapiana, Gianfranco Vitiello, Francesca Fabris, Sara Bindoli, Leonardo Punzi, Paola Galozzi, Paolo Sfriso
Background: Interleukin (IL)-1 plays a crucial role in the pathogenesis of Adult onset Still's disease (AOSD). Objectives: To evaluate the efficacy and safety of anakinra (ANA) and canakinumab (CAN) in a large group of AOSD patients. Methods: Data on clinical, serological features, and concomitant treatments were retrospectively collected at baseline and after 3, 6, and 12 months from AOSD patients (Yamaguchi criteria) referred by 18 Italian centers. Pouchot's score was used to evaluate disease severity. Results: One hundred forty patients were treated with ANA; 4 were subsequently switched to CAN after ANA failure...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28659798/il-1%C3%AE-inhibition-in-cardiovascular-complications-associated-to-diabetes-mellitus
#15
REVIEW
Concepción Peiró, Óscar Lorenzo, Raffaele Carraro, Carlos F Sánchez-Ferrer
Diabetes mellitus (DM) is a chronic disease that affects nowadays millions of people worldwide. In adults, type 2 diabetes mellitus (T2DM) accounts for the majority of all diagnosed cases of diabetes. The course of the T2DM is characterized by insulin resistance and a progressive loss of β-cell mass. DM is associated with a number of related complications, among which cardiovascular complications and atherosclerosis are the main cause of morbidity and mortality in patients suffering from the disease. DM is acknowledged as a low-grade chronic inflammatory state characterized by the over-secretion of pro-inflammatory cytokines, including interleukin (IL)-1β, which reinforce inflammatory signals thus contributing to the development of complications...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28624931/familial-mediterranean-fever-review-of-the-literature
#16
Mansour Alghamdi
Familial Mediterranean fever (FMF) is the most common monogenic periodic fever syndrome and characterized by recurrent episodes of fever, serositis, arthritis, dermal manifestations, and long-term renal complications. The MEFV gene was described in 1997 as the gene responsible for FMF and is inherited in autosomal recessive manner. It encodes mutated protein pyrin, an important player in the innate immune system and the component of inflammasome which leads to exaggerated inflammatory response through uncontrolled production of interleukin-1...
August 2017: Clinical Rheumatology
https://www.readbyqxmd.com/read/28589388/-efficacy-and-safety-analysis-of-off-label-treatment-with-biologics-in-autoinflammatory-diseases-experiences-from-a%C3%A2-german-registry%C3%A2-graid2
#17
F Proft, M Fleck, C Fiehn, H Schulze-Koops, M Witt, T Dörner, J C Henes
OBJECTIVE: To evaluate the safety and efficacy of therapy with biologics in patients with autoinflammatory diseases (AIF) or macrophage activating syndrome (MAS) in a real-life setting in Germany. METHODS: The German Register of Autoimmune Diseases 2 (GRAID2) is a retrospective, non-interventional, multicenter registry collecting data from all patients with inflammatory rheumatic diseases refractory to conventional therapy and treated with initial off-label biologics between August 2006 and December 2013...
June 6, 2017: Zeitschrift Für Rheumatologie
https://www.readbyqxmd.com/read/28588486/potential-of-il-1-il-18-and-inflammasome-inhibition-for-the-treatment-of-inflammatory-skin-diseases
#18
REVIEW
Gabriele Fenini, Emmanuel Contassot, Lars E French
In 2002, intracellular protein complexes known as the inflammasomes were discovered and were shown to have a crucial role in the sensing of intracellular pathogen- and danger-associated molecular patterns (PAMPs and DAMPs). Activation of the inflammasomes results in the processing and subsequent secretion of the pro-inflammatory cytokines IL-1β and IL-18. Several autoinflammatory disorders such as cryopyrin-associated periodic syndromes and Familial Mediterranean Fever have been associated with mutations of genes encoding inflammasome components...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28586272/pharmacological-treatment-options-for-cryopyrin-associated-periodic-syndromes
#19
REVIEW
Emmanuelle C Landmann, Ulrich A Walker
Cryopyrin-associated periodic syndromes (CAPS) are rare monogenic autoinflammatory diseases, comprising a spectrum of phenotypes of varying severity. CAPS are associated with gain-of-function mutations in the NLRP3 inflammasome, a multiprotein complex critical for the activation of IL-1ß, and are characterized by episodes of fever, urticaria-like rash, musculoskeletal, ocular, and neurological symptoms. Areas covered: Accounting for the pivotal role of IL-1ß in the pathogenesis of CAPS, three therapeutic options, all blocking the action of IL-1ß, are currently approved: anakinra, a recombinant IL-1 receptor antagonist, the IL-1 trap rilonacept and canakinumab, a monoclonal anti-IL-1ß antibody...
August 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28585601/canakinumab-treatment-in-four-children-with-colchicine-resistant-familial-mediterranean-fever
#20
Solmaz Ozkan, Bulent Atas
Familial Mediterranean Fever (FMF) is an autosomal recessive and autoinflammatory disease, characterized with inflammation of serous membranes such as peritoneum, pleura, synovium with fever and pain. Colchicine is the main treatment of FMF, but 5-10 % of patients are unresponsive to colchicine. We report using anti-interleukin-1 agents anakinra and canakinumab in four colchicine-resistant patients who were successfully treated. Three of the patients were siblings.
June 2017: JPMA. the Journal of the Pakistan Medical Association
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