Canakinumab Anti-Inflammatory Thrombosis Outcome Study - CANTOS
Contribution To Literature:
The CANTOS trial showed that canakinumab (150 mg) was superior to placebo at preventing adverse cardiac events.
The goal of the trial was to evaluate canakinumab compared with placebo among patients with a history of myocardial infarction (MI) and elevated high-sensitivity C-reactive protein (hsCRP). Canakinumab is a monoclonal antibody targeting interleukin-1β.
Patients with MI and elevated hsCRP were randomized to canakinumab 50 mg (n = 2,170) vs. canakinumab 150 mg (n = 2,284) vs. canakinumab 300 mg (n = 2,263) vs. placebo (n = 3,344). The study drug was administered subcutaneously once every 3 months.
- Total number of enrollees: 10,061
- Duration of follow-up: median 3.7 years
- Mean patient age: 61 years
- Percentage female: 26%
- Percentage with diabetes: 40%
- Median low-density lipoprotein cholesterol: 82 mg/dl
- History of MI
- hsCRP ≥2 mg/L
- Chronic or recurrent infection
- High risk for tuberculosis or HIV
- History of cancer
- Immunocompromised state
- Systemic use of anti-inflammatory treatment
The primary outcome, incidence of cardiovascular death, MI, or stroke, occurred in 4.11/100 person-years of the 50 mg group vs. 3.86/100 person-years of the 150 mg group vs. 3.90/100 person-years of the 300 mg group vs. 4.50/100 person-years of the placebo group (p = 0.02 for 150 mg group vs. placebo; other comparisons nonsignificant).
- hsCRP reduction from baseline vs. placebo: 26% greater in the 50 mg group, 37% greater in the 150 mg group, and 41% greater in the 300 mg group (p < 0.001 for all comparisons with placebo)
- Fatal infection or sepsis: 0.31/100 person-year in the combined canakinumab vs. 0.18/100 person-year in the placebo group (p = 0.02)
Among patients with a history of MI and elevated hsCRP, canakinumab was effective at preventing adverse cardiac events over a median of 3.7 years. The only dose that achieved significance after multiplicity-adjusted threshold for statistical significance was the 150 mg group. Canakinumab was effective at reducing hsCRP in a dose-response relationship. Canakinumab was associated with an increased risk of fatal infection or sepsis despite exclusion of patients with chronic or recurrent infection.
Ridker PM, Everett BM, McFadyen JG, et al., on behalf of the CANTOS Trial Group. Antiinflammatory therapy with canakinumab for atherosclerotic disease. N Engl J Med 2017;377:1119-31.
Editorial: Harrington RA. Targeting Inflammation in Coronary Artery Disease. N Engl J Med 2017;377:1197-8.
Ridker PM, McFadyen JG, Thuren T, et al., on behalf of the CANTOS Trial Group. Effect of interleukin-1β inhibition with canakinumab on incident lung cancer in patients with atherosclerosis: exploratory results from a randomised, double-blind, placebo-controlled trial. Lancet 2017;Aug 27:[Epub ahead of print].
Presented by Dr. Paul M. Ridker at the European Society of Cardiology Congress, Barcelona, Spain, August 27, 2017.
Keywords: Antibodies, Monoclonal, Anti-Inflammatory Agents, Atherosclerosis, Cholesterol, LDL, C-Reactive Protein, Dyslipidemias, ESC Congress, ESC2017, Inflammation, Myocardial Infarction, Primary Prevention, Thrombosis, Sepsis, Stroke
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