Inflammatory cytokines, such as interleukin (IL)-1β, alter iron homeostasis and erythropoiesis, resulting in anemia, but whether inhibition of IL-1β can reverse these effects was unclear until recently. A new randomised study that was published in Annals of Internal Medicine indicates that this seems to be the case.
The CANTOS (Canakinumab Anti-inflammatory Thrombosis Outcomes Study) study involved 8683 participants without anemia, and 1303 participants with anemia in 39 countries. Test subjects received either placebo or canakimumab (50, 100 or 300 mg) in a subcutaneous administration every three months. Primary outcome was the incidence of anemia (hg level <130 g/L in men or <120 g/L in women).
Anemia incidence increased with rising baseline levels of high-sensitivity C-reactive protein (hsCRP), and both hsCRP and IL-6 decreased among participants receiving canakinumab compared with the placebo group. During a median follow-up of 3.7 years, participants without baseline anemia who received canakinumab at any dosage had significantly less incident anemia than those who received placebo (hazard ratio, 0.84 [95% CI, 0.77 to 0.93]; P < 0.001).
Compared with placebo, the greatest benefits of IL-1β inhibition on developing anemia were observed among participants with the most robust anti-inflammatory response. Among those with baseline anemia, canakinumab increased mean hemoglobin levels by 11.3 g/L (P < 0.001) compared with placebo after 2 years of treatment. Canakinumab also increased the risk for infection and was associated with mild cases of thrombocytopenia and neutropenia, none of which was grade 3 or higher.
The trial data provide proof of principle that inflammation inhibition through the IL-1β/IL-6 signaling pathway reduces the incidence of anemia and improves hemoglobin levels in patients with anemia.