What Are the Factors That Influence Response to Canakinumab Therapy?

Inhibition of the proinflammatory cytokine interleukin (IL)-1β via canakinumab appears to be feasible as a treatment for patients with concurrent anemia and clonal hematopoiesis mutations, according to a post-hoc analysis of the CANTOS study, published in Blood Advances.

“A higher association of hematological response to canakinumab was observed in patients with concurrent [clonal hematopoiesis] mutations and anemia compared with patients without [clonal hematopoiesis] mutations or with only [clonal hematopoiesis] mutations without cytopenia,” wrote Janghee Woo, MD, PD, from the Novartis Institutes for Biomedical Research in Cambridge, Massachusetts.

This analysis included 4,595 patients from CANTOS who were treated with either canakinumab or placebo. Researchers found that incident anemia was more frequent in patients with clonal hematopoiesis mutations, but was ameliorated by canakinumab treatment.

Canakinumab treatment was significantly associated with higher hemoglobin ranges in patients with clonal hematopoiesis mutations with anemia versus those with either mutations or anemia alone. Additionally, the presence of clonal hematopoiesis mutations was associated with proteomic inflammation markers, defense response to infection, and markers for high-risk cardiovascular disease compared with patients without mutations.

Canakinumab had the greatest suppression of hepcidin, proinflammatory cytokines, myeloid activation, and complement pathways, as well as reversal of deregulated pathways, in patients with mutations and anemia.

“These results are hypothesis-generating and warrant further studies,” suggested Dr. Woo and colleagues.

Reference

Woo J, Lu D, Lewandowski A, et al. Effects of IL-1β inhibition on anemia and clonal hematopoiesis in the randomized CANTOS trial. Blood Adv. 2023;7(24):7471-7484. doi:10.1182/bloodadvances.2023011578