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Crystalline Arthritis
Published in Jason Liebowitz, Philip Seo, David Hellmann, Michael Zeide, Clinical Innovation in Rheumatology, 2023
Anti-IL-1β biologics have limited gastrointestinal, renal, and metabolic adverse effects but are costlier than traditional agents. In a trial comparing anakinra to usual care (colchicine, naproxen, or prednisone) for treating gout flares, anakinra was noninferior with respect to pain reduction.26 Similarly, canakinumab in the β-RELIEVED and β-RELIEVED-II trials demonstrated efficacy for treating and preventing gout flares in those with frequent flares (≥ 3/year) for whom traditional agents were deemed inappropriate. One dose of canakinumab 150 mg was superior to triamcinolone acetonide 40 mg to prevent new and delay subsequent flares, although cytopenias and infections were more common with canakinumab.27
Convalescent Plasma and Antibody Therapy in COVID-19
Published in Debmalya Barh, Kenneth Lundstrom, COVID-19, 2022
Didem Rıfkı, Eymen Ü. Kılıç, Şükrü Tüzmen
Subcutaneous canakinumab administration (against human IL-1) was associated with a rapid reduction in the systemic inflammatory response and an increase in oxygenation without causing any serious side effects [29]. It was also associated with a reduced need for intrusive mechanical ventilation, earlier hospital discharge, and a better prognosis than standard of care, according to previous studies [29] (Table 8.2). As a result, it represents a therapeutic alternative for adult hospitalized patients with moderate to serious non-ICU complications [30].
Oxidative Stress, Inflammation, Immune System and Hypertension
Published in Giuseppe Mancia, Guido Grassi, Konstantinos P. Tsioufis, Anna F. Dominiczak, Enrico Agabiti Rosei, Manual of Hypertension of the European Society of Hypertension, 2019
Damiano Rizzoni, Livia L. Camargo, Francisco J. Rios, Augusto C. Montezano, Rhian M. Touyz
An important study recently highlighted the significance of inflammation, immunity and atherosclerotic vascular disease in clinical medicine. A randomized double-blind trial in over 10,000 patients investigated the effects of canakinumab, a therapeutic monoclonal antibody targeting IL-1β, on nonfatal myocardial infarction, nonfatal stroke or cardiovascular death (CANTOS study). Results demonstrated that anti-inflammatory therapy targeting IL-1β, at a dose of 150 mg every 3 months, resulted in a lower recurrent cardiovascular event versus placebo, independent of lipid lowering. This was associated with reduced levels of proinflammatory markers, IL-6 and C-reactive protein. This large clinical trial provides important evidence that innate immunity can be modulated to reduce cardiovascular risk. Targeting inflammation may be a potentially interesting strategy to reduce atherosclerotic disease. However, whether this approach would also influence blood pressure reduction in hypertension is unknown.
Current and emerging drugs for the treatment of atherosclerosis: the evidence to date
Published in Expert Review of Cardiovascular Therapy, 2022
Ali A. Rizvi, Djordje S. Popovic, Nikolaos Papanas, Anca Pantea Stoian, Wael Al mahmeed, Amirhossein Sahebkar, Andrej Janez, Manfredi Rizzo
Canakinumab is a human anti-interleukin-1β monoclonal antibody [71]. Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS) was a randomized, double-blind, placebo-controlled trial [72]. It has involved 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein (hsCRP) level of ≥2 mg/l. The CANTOS atrial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every three months) with the placebo group. The primary efficacy endpoint was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. Unlike the other two doses, the canakinumab dose of 150 mg met the prespecified multiplicity-adjusted threshold for statistical significance for the primary endpoint. In addition, Canakinumab was associated with a higher incidence of fatal infection than placebo [71].
Anti-inflammatory strategies for atherosclerotic artery disease
Published in Expert Opinion on Drug Safety, 2022
Federica Agnello, Davide Capodanno
Canakinumab is a human monoclonal antibody anti IL-1β, currently approved for a group of rare auto-inflammatory syndromes. The CANTOS trial (The Canakinumab Antiinflammatory Thrombosis Outcome Study) of canakinumab is historically recognized as the first study to confirm the so-called inflammatory hypothesis. The trial enrolled 1,061 patients with prior MI and a pro-inflammatory state (hs-CRP >2 mg/L), who were randomized to different doses of canakinumab (50 mg, 150 mg, 300 mg) or placebo. In the group treated with 150 mg of canakinumab, after 3.2 years of follow-up, a 15% relative risk reduction compared with placebo was observed with respect to the composite of combined MI, non-fatal stroke or cardiovascular death (HR 0.85, 95% CI 0.74–0.98, p = 0.02), coupled with a 35% reduction in hs-CRP, despite no changes in LDL cholesterol levels were observed [76]. Of note, after the first dose, patients with persistent hs-CRP value >2 mg/L did not experience a significant clinical benefit. The European and United States regulatory authorities did not approve canakinumab for secondary prevention of cardiovascular events, mostly because of the risk of sepsis and fatal infections observed in CANTOS. In fact, patients who received canakinumab experienced higher rates of neutropenia leading to death, especially in older and diabetic patients. Moreover, the high cost of canakinumab makes it a less favorable strategy for widespread use compared with other more economic compounds [77,78].
Canakinumab injection for the treatment of active Still’s disease, including adult-onset Still’s disease
Published in Expert Opinion on Orphan Drugs, 2021
Alessandro Tomelleri, Corrado Campochiaro, Giacomo De Luca, Nicola Farina, Giulio Cavalli, Lorenzo Dagna
Additional data on the use of canakinumab in adults were provided by Feist et al., who reported the results of a pooled analysis of 4 sJIA studies gathering patients into 3 groups according to an age criterion [77]. Of note, one of these groups included 29 patients diagnosed in the early adolescence but older adolescents or young adults (mean age, 17.1 ± 0.95 years) at canakinumab start – and therefore considered to represent an AOSD population. The main efficacy outcomes in this subgroup of patients were comparable to those in children (2 to <12 years) and young adolescents (12 to <16 years). Specifically, they described a remarkable drop of inflammatory laboratory markers along with a significant improvement of both articular manifestations and quality of life measures. These responses were rapidly achieved and consistently maintained at 85 days.