Canakinumab did not meet the primary endpoint of reducing daily sickle cell anemia (SCA)-related pain, but was associated with improvements in inflammation markers, occurrence of SCA-related adverse events (AEs), hospitalizations, pain, and absence from school or work, according to the results of randomized, phase 2a study published in the journal Blood.

Upregulation of proinflammatory cytokines, including interleukin (IL)–1β, are modulated by the inflammasome, which is activated by the excessive intravascular release of intracellular contents of damaged red blood cells.

“We hypothesized that IL-1β blockade by canakinumab in patients with SCA would reduce markers of inflammation and clinical disease activity,” the authors wrote.

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The multicenter, phase 2a trial randomly assigned patients aged 8 to 20 with SCA in a double-blind setting to receive 6 doses of canakinumab or matched placebo. At the end of this period, patients continued in an open-label period in which all patients received canakinumab without unblinding of the randomized period. The primary endpoint was reduction of daily SCA-related pain averaged over weeks 8 to 12 compared with baseline. Secondary endpoints included perceived fatigue, analgesic use, and school or work attendance.

All patients had experienced a minimum of 2 vaso-occlusive pain episodes, had a highly sensitive C-reactive protein level of >1.0 mg/L, and detectable background pain. The mean age was 15.7, 57% were male, 51% were Black, and 45% were White. The median daily dose of hydroxyurea was 1000 mg.

Although canakinumab decreased daily pain scores during the first 12 weeks, which was maintained to week 24, the difference did not meet the prespecified criteria for clinically meaningful difference from baseline.

However, canakinumab resulted in improvements in other patient-reported outcomes. Average opioid use during a 24-week period was reduced to 26.6 days with canakinumab compared with 47.8 days with placebo. Nonopioid analgesic use increased in the canakinumab arm compared with the placebo arm at 112.2 and 106.0 days, respectively, suggesting more patients in the canakinumab arm used non-opioid agents to relieve pain.

Daily fatigue ratings decreased steadily during the 24-week period in the canakinumab arm, but remained similar throughout the same time period in the placebo arm, resulting in a clinically meaningful difference by week 20.

School or work absences were reduced with canakinumab beginning at 16 weeks into treatment compared with baseline, whereas patients in the placebo group experienced an increase in absences relative to baseline.

Additional outcomes were also improved with canakinumab. The number of hospitalizations and the overall time spent in the hospital were lower with canakinumab compared with placebo. Patients in the canakinumab group were hospitalized for acute pain crises, whereas patients in the placebo group were hospitalized for severe SCA-related complications.

Canakinumab also resulted in progressive reductions in hsCRP and absolute levels of leukocytes, neutrophils, and monocytes. There were no changes in oxygen saturation or hemolysis parameters.

The authors concluded that “these study results suggest that selective blockade of IL-1β-mediated inflammation by canakinumab in adolescent and young adults with SCA could lead to therapeutic benefits without major safety issues.”

Disclosures: This study was funded by Novartis Pharma AG. Please see the original reference for a full list of disclosures.


Rees DC, Kilinc Y, Unal S, et al. A randomized, placebo-controlled, double-blind trial of canakinumab in children and young adults with sickle cell anemia. Blood. 2022;139:2642-2652. doi:10.1182/blood.2021013674