2017, CANTOS Trial: Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease, NEJM
The CANTOS trial evaluated the inflammatory nature of coronary artery disease where hypothesis was that decreasing the inflammation marker such as interleukin 1B will result in lower incidence of cardiovascular events. For this purpose, canakinumab which is a monoclonal antibody against IL-1B was tested against a placebo. The only dose that achieved significance after multiplicity-adjusted threshold for statistical significance was the 150 mg group.
The patients that responded best were those who achieved on-treatment hsCRP concentrations less than 2 mg/L. The authors observed a 25% decrease in major cardiovascular events in these patients. This was in contrast to those who continued to elevated hsCRP levels despite treatment. Based on this observation, the CANTOS trial authors concluded, “the magnitude of hsCRP reduction following a single dose of canakinumab might provide a simple clinical method to identify individuals most likely to accrue the largest benefit from continued treatment.”
With CANTOS trial results, Dr. Paul Ridker et al. decided to take a step forward and tried to inhibit the chain of inflammatory markers including IL-1, IL6 and CRP. They utilized methotrexate for this purpose and described their results in the CIRT trial.