Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease
Language English Country United States Media print-electronic
Document type Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't
Grant support
K23 NS073806
NINDS NIH HHS - United States
PubMed
28845751
DOI
10.1056/nejmoa1707914
Knihovny.cz E-resources
- MeSH
- Anti-Inflammatory Agents administration & dosage adverse effects MeSH
- Atherosclerosis blood drug therapy MeSH
- C-Reactive Protein metabolism MeSH
- Stroke prevention & control MeSH
- Double-Blind Method MeSH
- Antibodies, Monoclonal, Humanized MeSH
- Incidence MeSH
- Myocardial Infarction drug therapy prevention & control MeSH
- Infections etiology MeSH
- Interleukin-1beta antagonists & inhibitors immunology MeSH
- Cardiovascular Diseases epidemiology mortality MeSH
- Middle Aged MeSH
- Humans MeSH
- Lipids blood MeSH
- Antibodies, Monoclonal administration & dosage adverse effects MeSH
- Neutropenia chemically induced MeSH
- Secondary Prevention MeSH
- Aged MeSH
- Dose-Response Relationship, Drug MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Research Support, Non-U.S. Gov't MeSH
- Randomized Controlled Trial MeSH
- Names of Substances
- Anti-Inflammatory Agents MeSH
- C-Reactive Protein MeSH
- canakinumab MeSH Browser
- Antibodies, Monoclonal, Humanized MeSH
- Interleukin-1beta MeSH
- Lipids MeSH
- Antibodies, Monoclonal MeSH
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. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P=0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P=0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P=0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P=0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P=0.31). CONCLUSIONS: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846 .).
References provided by Crossref.org
The Perivascular Fat Attenuation Index: Bridging Inflammation and Cardiovascular Disease Risk
The Use of Autologous Cell Therapy in Diabetic Patients with Chronic Limb-Threatening Ischemia
Microenvironmental regulation of T-cells in pulmonary hypertension
Rapid Drop in Coronary Heart Disease Mortality in Czech Male Population-What Was Actually behind It?
Specialized Proresolving Lipid Mediators: A Potential Therapeutic Target for Atherosclerosis
Cholesterol in the Cell Membrane-An Emerging Player in Atherogenesis
Adipose tissue macrophages and atherogenesis - a synergy with cholesterolaemia
Interleukin-1 Blockade in Polygenic Autoinflammatory Disorders: Where Are We now?
Subsequent Event Risk in Individuals With Established Coronary Heart Disease
ClinicalTrials.gov
NCT01327846, NCT01327846