CANTOS — Canakinumab Anti-Inflammatory Trial

Design

CANTOS randomised >10,000 adults with prior myocardial infarction and elevated hsCRP (≥2 mg/L) despite optimal medical therapy to one of three doses of canakinumab (an anti-IL-1β monoclonal antibody) subcutaneously every 3 months versus placebo, for ~4 years.

Findings

• Cardiovascular: 15% relative reduction in major adverse cardiovascular events at the 150 mg dose.
• Inflammation: substantial reductions in hsCRP and IL-6, no change in lipids.
• Cancer (unexpected): significant reduction in lung-cancer incidence and lung-cancer mortality — consistent with inflammation contributing to lung-cancer biology.
• Trade-off: increased fatal infections (~1 extra per 1,000 patient-years).
• No effect on all-cause mortality in primary analysis.

Why it matters

CANTOS established that inflammation is a causal driver of atherosclerosis (not just a marker) by lowering inflammation without touching lipids and still reducing events. It validated the “inflammaging” framework and motivated subsequent trials of colchicine, ziltivekimab (IL-6 blockade), and others.

Commercial follow-up

Canakinumab is not used in routine cardiovascular practice (cost, infection risk). Colchicine (LoDoCo2) emerged as a low-cost anti-inflammatory alternative with modest event reduction.

Related entries

Chronic inflammation, hsCRP, IL-6, Cardiovascular disease.