CANTOS Trial of Canakinumab

Canakinumab is a humanized monoclonal antibody targeting interleukin-1β. Experimental and clinical information had suggested that reducing inflammation even without affecting lipid levels may reduce the risk of cardiovascular disease. This novel concept was tested in the CANTOS trial involving over ten thousand patients with prior myocardial infarction and elevated high sensitivity C-reactive protein (hsCRP). Three dosage schedules of canakinumab administered subcutaneously every three months, was compared to placebo. Primary efficacy endpoint for the CANTOS trial was nonfatal myocardial infarction, nonfatal stroke or cardiovascular death.

Median reduction in hsCRP ranged from 26 to 41 percent in the different dosage groups, at 48 months. There was no reduction in lipid levels with canakinumab. The middle dosage scheme of 150 mg canakinumab every three months led to a significantly lower rate of recurrent cardiovascular events. Canakinumab targets the interleukin-1β innate immunity pathway. An important downside noted was higher incidence of fatal infection than placebo. An interesting advantage noted was lower reports of arthritis, gout, osteoarthritis and cancer mortality in the canakinumab group.

Potential roles for the proinflammatory cytokine interleukin-1β in cardiovascular disease are induction of procoagulant activity, promotion of monocyte and leukocyte adhesion to vascular endothelial cells and growth of vascular smooth muscle cells. These have been implicated in the development of atherosclerotic plaques.

Reference

1. Ridker PM, Everett BM, Thuren T, MacFadyen JG, Chang WH, Ballantyne C, Fonseca F, Nicolau J, Koenig W, Anker SD, Kastelein JJP, Cornel JH, Pais P, Pella D, Genest J, Cifkova R, Lorenzatti A, Forster T, Kobalava Z, Vida-Simiti L, Flather M, Shimokawa H, Ogawa H, Dellborg M, Rossi PRF, Troquay RPT, Libby P, Glynn RJ; CANTOS Trial Group. Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease. N Engl J Med. 2017 Sep 21;377(12):1119-1131. doi: 10.1056/NEJMoa1707914. Epub 2017 Aug 27. PMID: 28845751.