Efficacy and safety of pharmacological interventions for managing sickle cell disease complications in children and adolescents: Systematic review with network meta‐analysis

Abstract

This study aimed to synthesize the evidence on the effects of disease‐modifying agents for managing sickle cell disease (SCD) in children and adolescents by means of a systematic review with network meta‐analyses, surface under the cumulative ranking curve (SUCRA) and stochastic multicriteria acceptability analyses (SMAA) (CRD42022328471). Eightteen randomized controlled trials (hydroxyurea [n = 7], l‐arginine [n = 3], antiplatelets [n = 2], immunotherapy/monoclonal antibodies [n = 2], sulfates [n = 2], docosahexaenoic acid [n = 1], niprisan [n = 1]) were analyzed. SUCRA and SMAA demonstrated that hydroxyurea at higher doses (30 mg/kg/day) or at fixed doses (20 mg/kg/day) and immunotherapy/monoclonal antibodies are more effective for preventing vaso‐occlusive crisis (i.e., lower probabilities of incidence of this event; 14, 25, and 30%, respectively), acute chest syndrome (probabilities ranging from 8 to 30%), and needing of transfusions (11–31%), while l‐arginine (100–200 mg/kg) and placebo were more prone to these events. Therapies were overall considered safe; however, antiplatelets and sulfates may lead to more severe adverse events. Although the evidence was graded as insufficient and weak, hydroxyurea remains the standard of care for this population, especially if a maximum tolerated dose schedule is considered.

Sickle Cell Disease: Current Drug Treatments and Functional Foods with Therapeutic Potential

“…However, as individuals age, various factors may intervene, influencing the symptomatic expression of SCD [ 10 ]. Individuals with SCA experience reduced red blood cell flexibility due to polymerization, resulting in rheological and biochemical alterations that impede blood flow, ultimately leading to vaso-occlusive crises (VOCs) [ 10 , 11 ]. Studies in genetic mapping and genome-wide association have identified specific genetic loci associated with SCA, including B-cell lymphoma/leukemia 11A (BCL11A), an Xmn1 variant located upstream of the hemoglobin subunit gamma 1 (HBG1), and the HBS1L-MYB intergenic region.…”

“…However, as individuals age, various factors may intervene, influencing the symptomatic expression of SCD [10]. Individuals with SCA experience reduced red blood cell flexibility due to polymerization, resulting in rheological and biochemical alterations that impede blood flow, ultimately leading to vaso-occlusive crises (VOCs) [10,11]. Studies in genetic mapping and genome-wide association have identified specific genetic loci associated with SCA, including B-cell lymphoma/leukemia 11A (BCL11A), an Xmn1 variant located upstream of the hemoglobin subunit gamma 1 (HBG1), and the HBS1L-MYB in- SCD can manifest in various clinical features, including abnormal eye growth in the retina (proliferative retinopathy), tissue death due to blocked blood flow (vascular necrosis), prolonged painful erection (priapism), dilute urine (hyposthenuria), episodes of severely reduced red blood cell production (aplastic crises), kidney problems (nephropathy), and lung disease [5].…”