Author(s): Tonin, Fernanda ; Ginete, Catarina ; Ferreira, Joana ; Delgadinho, Mariana ; Santos, Brígida ; Fernandez‐Llimos, Fernando ; Brito, Miguel
Date: 2023
Persistent ID: http://hdl.handle.net/10400.21/15924
Origin: Repositório Científico do Instituto Politécnico de Lisboa
Subject(s): Adolescents; Children; Disease-modifying agents; Sickle cell disease; Meta-analysis; Systematic review; FCT_UIDB/05608/2020; FCT_UIDP/05608/2020
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, the surface under the cumulative ranking curve (SUCRA) and stochastic multicriteria acceptability analyses (SMAA) (CRD42022328471). Eighteen 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.
