In patients with sickle cell anemia (SCA), the excessive intravascular release of lysed cellular contents from damaged red blood cells (RBCs) can activate the inflammasome, a multiprotein oligomer that promotes the maturation and secretion of proinflammatory cytokines like interleukin-1β (IL-1β). Researchers expected that canakinumab, which blocks IL-1, will lower inflammatory indicators and clinical disease activity in individuals with SCA. Patients aged 8 to 20 years old with SCA (HbSS or HbSβ0-thalassemia), a history of acute pain episodes, and an elevated high-sensitivity C-reactive protein >1.0 mg/L at screening were randomized 1:1 to receive 6 monthly treatments with 300 mg subcutaneous canakinumab or placebo in the randomized, double-blind, multicenter phase 2a study. Electronic patient-reported outcomes, hospitalization rate, adverse events (AEs), and major AEs were all measured at baseline and weeks 4, 8, 12, 16, 20, and 24. (SAEs).
All but one of the 49 patients in the study were on stable hydroxyurea treatment. Although the primary goal (a reduction in pain) was not met, patients who received canakinumab had lower levels of inflammation, fewer SCA-related AEs, and SAEs, and fewer and longer hospitalizations, as well as improvements in pain intensity, fatigue, and absences from school or work, compared to those who received placebo. Treatment benefits on weight were discovered in a post hoc study, but only in pediatric patients. There were no treatment-related SAEs and no new safety signals with canakinumab. The data showed that canakinumab, a specific IL-1 blocker, can lower the inflammation associated with SCA, potentially resulting in therapeutic advantages.