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.