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Papers of the Week

Papers: 26 Feb 2022 - 4 Mar 2022

Pharmacology/Drug Development

2022 Feb 28


A randomized, placebo-controlled, double-blind trial of canakinumab in children and young adults with sickle cell anemia.


Rees DC, Kilinc Y, Unal S, Dampier CD, Pace B, Kaya B, Trompeter S, Odame I, Mahlangu J, Unal S, Brent J, Grosse R, Fuh B, Inusa BPD, Koren A, Leblebisatan G, Levin C, McNamara E, Meiser K, Hom D, et al.
Blood. 2022 Feb 28.
PMID: 35226723.


Excessive intravascular release of lysed cellular contents from damaged red blood cells (RBCs) in patients with sickle cell anemia (SCA) can activate the inflammasome, a multiprotein oligomer promoting maturation and secretion of pro-inflammatory cytokines, including interleukin 1-beta (IL-1b). We hypothesized that IL-1b blockade by canakinumab in patients with SCA would reduce markers of inflammation and clinical disease activity. In this randomized, double-blind, multi-center phase 2a study, patients aged 8-20 years old with SCA (HbSS or HbSb0thalassemia), history of acute pain episodes and elevated hsCRP >1.0 mg/L at screening were randomized 1:1 to received 6 monthly treatments with 300 mg s.c. canakinumab or placebo. Measured outcomes at baseline and weeks 4, 8, 12, 16, 20 and 24 included electronic patient-reported outcomes, hospitalization rate and adverse events (AEs) and serious AEs (SAEs). All but one of the 49 enrolled patients were receiving stable background hydroxyurea therapy. Although the primary objective (pre-specified reduction of pain) was not met, compared to placebo-arm patients, canakinumab-treated patients had reductions in markers of inflammation, occurrence of SCA-related AE and SAE, and number and duration of hospitalizations, as well as trends for improvement in pain intensity, fatigue and absences from school or work. Post-hoc analysis revealed treatment effects on weight, restricted to pediatric patients. Canakinumab was well tolerated with no treatment-related SAEs and no new safety signal. These findings demonstrate that the inflammation associated with SCA can be reduced by selective IL-1b blockade by canakinumab with potential for therapeutic benefits. This trial was registered at www.clinicaltrials.gov as NCT02961218.