Canakinumab Antiinflammatory Thrombosis Outcome Study (CANTOS) trial
Last reviewed 03/2021
Canakinumab Antiinflammatory Thrombosis Outcome Study (CANTOS) trial
Canakinumab targets IL-1beta, a highly specific mediator of inflammation
- the IL-1 pathway has considerable preclinical data to support its involvement
in atherogenesis
- atherogenesis can be described as an inflammatory processs that leads
to lipid accumulation in monocyte-derived macrophages that become foam
cells
- atherogenesis can be described as an inflammatory processs that leads
to lipid accumulation in monocyte-derived macrophages that become foam
cells
- CANTOS investigators tested the hypothesis that inhibiting the action of
the cytokine interleukin-1 (IL-1) beta would have beneficial effects on a
composite endpoint in patients with a prior myocardial infarction and a high-sensitivity
C-reactive protein (hsCRP) level that constituted a vascular risk (=2 mg/L)
(2)
- three different doses of the IL-1 beta neutralising antibody Canakinumab
were tested against placebo over 48 months
- 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.
- 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.
- a dose-dependent reduction in hsCRP was demonstrated without significant
alteration in lipid levels
- Canakinumab did not reduce lipid levels from baseline
- there was a dose graded reduction in the primary endpoint of first
occurrence of nonfatal myocardial infarction, nonfatal stroke, or
cardiovascular death with the pre-specified, complex statistical threshold
for primary and secondary endpoints being met with the 150-mg dose.
There was no difference in all-cause mortality, however, there was
a significant increase in infection-related deaths when all treated
patients were compared with placebo
- the study authors concluded "Antiinflammatory therapy targeting the interleukin-1ß 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"
- Canakinumab did not reduce lipid levels from baseline
- three different doses of the IL-1 beta neutralising antibody Canakinumab
were tested against placebo over 48 months
Reference:
- Tabas I, Lichtman AH. Monocyte-macrophages and T cells in atherosclerosis. Immunity 2017;47:621-34
- Ridker PM, Everett BM, Thuren T, et al. Antiinflammatory therapy with canakinumab for atherosclerotic disease. N Engl J Med 2017;377:1119-31