The concurrent CH mutations and anemia enhance the suppression of inflammatory pathways mediated by canakinumab. Pre- and post-treatment proteomic data from SomaScan and individual cytokine ELISA discovered more substantial suppression of inflammatory pathways by canakinumab in patients with CH mutations and anemia (CCUS) than patients with only CH mutations (CHIP). (A) Forest plot of mean differences in change of IL-6 (left), hepcidin (middle), and TNF-α (right) levels at months 3 and 12 in patients with CH mutations compared to those in patients without CH mutations, adjusted for baseline hemoglobin, hsCRP, and age. (B) Forest plot of mean differences in change of IL-6, hepcidin, and TNF-α levels at months 3 (top) and 12 (bottom) in patients with baseline anemia, compared to those in patients without baseline anemia among patients with CH mutations, adjusted for baseline hemoglobin, hsCRP, and age. (C) Changes of pathway enrichment scores associated with defense and immune response from baseline to months 3 (top) and 12 (bottom) of canakinumab treatment in patients stratified based on the presence of baseline anemia among patients with CH mutations, adjusted for baseline hemoglobin, hsCRP, and age. (D) Association of inflammation and erythroid response to canakinumab in patients with only CH mutations (CHIP) and concurrent CH mutations and anemia (CCUS). More elevated levels of inflammation and higher response to canakinumab were observed in patients with CCUS than in those with CHIP or no CH mutations.