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Comparative efficacy and safety of pharmacological interventions for sickle cell disease in children and adolescents: a network meta-analysis

2023-04Conference object Open access
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dc.contributor.authorTonin, Fernanda
dc.contributor.authorGinete, Catarina
dc.contributor.authorFerreira, J.
dc.contributor.authorDelgadinho, Mariana
dc.contributor.authorFernandez-Llimos, Fernando
dc.contributor.authorBrito, Miguel
dc.date.accessioned2023-08-25T11:56:18Z
dc.date.available2023-08-25T11:56:18Z
dc.date.issued2023-04
dc.description.abstractBackground: Sickle cell disease (SCD), an inherited hemoglobinopathy characterized by anemia, severe pain, acute chest syndrome (ACS), and vaso-occlusive crisis (VOC), has an important impact on morbidity and mortality worldwide, especially in the pediatric population (over 50% die before age of 5). Although few treatment options are available, new disease-modifying therapies, intended to prevent or reduce SCD-related complications are under development. Previous systematic reviews are limited to adult patients or focused only on gathering data on a few therapies. Aims: Our aim was to synthetize the evidence on the efficacy and safety profiles of pharmacological interventions for managing SCD in children and adolescents. Methods: A systematic review with searches in PubMed, Scopus, and Web of Science was performed (May-2022). The protocol is registered at PROSPERO CRD42022328471. We included randomized controlled trials comparing any disease-modifying agent used to treat SCD complications in patients under 18 years old. The outcomes of interest included: VOC, ACS, transfusions, hospital admission, discontinuation, and serious adverse events. Data were pooled by means of Bayesian network meta-analyses with the surface under the cumulative ranking curve analyses (SUCRA). Results were reported as odds ratio (OR) with 95% credibility intervals (CrI). Additionally, stochastic multicriteria acceptability analyses (SMAA) were performed. The methodological quality of the trials and certainty of evidence were evaluated through RoB 2.0 tool and the GRADE approach, respectively. Results: Overall, 17 randomized controlled trials (n=1,972 patients) published between 1982-2022, conducted mostly in Africa (41%) and North America (35%) were included for analyses. Around one-third of the trials were restricted to homozygous patients for the SCD allele (SS HMZ); yet when reported, patients with heterozygous S-C combination represented less than 30% of the population. Males accounted for 49.0% of the cases, with ages varying from 1 to 19 years old. Almost all trials (n=15, 88.2%) directly compared active drugs with placebo. The evaluated interventions were: hydroxyurea [n=6 trials], L-arginine [n=3], antiplatelets [n=2], immunotherapy/monoclonal antibodies [n=2], sulfates [n=2], docosahexaenoic acid [n=1], niprisan [n=1] (Figure 1). SUCRA and SMAA revealed that immunotherapy/monoclonal antibodies and hydroxyurea 20 mg/kg are potentially more effective against ACS (17% and 24% probabilities, respectively), VOC (around 29% and 20%, respectively) and needing of transfusions (around 25%), while L-arginine (100-200 mg/kg) and placebo were more associated with these events. Although therapies were overall considered safe, antiplatelet and sulfates may lead to more discontinuations and severe adverse events (uncertainty evidence). Results were similar between age subgroups (<10 years vs. 10-19 years). Summary - Conclusion: The available evidence on the effect of drugs on managing SCD in children and adolescents is still insufficient and weak. No clear definition and reporting criteria for some outcomes exist. Hydroxyurea 20 mg/kg/day may remain the standard of care for these patients, however, long-term, well-designed trials comparing new immunotherapy/monoclonal antibodies should be performed. The use of monotherapies with L-arginine, antiplatelets, or sulfates should be avoided given the poor benefit-risk ratio for this population.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationTonin FS, Ginete C, Ferreira J, Delgadinho M, Fernandez-Llimos F, Brito M. Comparative efficacy and safety of pharmacological interventions for sickle cell disease in children and adolescents: a network meta-analysis. In: Abstract Book for the 17th Annual Sickle Cell and Thalassaemia Conference. HemaSphere. 2023;7(Suppl 1):46.pt_PT
dc.identifier.doi10.1097/01.HS9.0000928488.59931.31pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.21/16411
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherLippincott Williams & Wilkinspt_PT
dc.relation.publisherversionhttps://journals.lww.com/hemasphere/fulltext/2023/04001/5588995_comparative_efficacy_and_safety_of.90.aspxpt_PT
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/pt_PT
dc.subjectSickle cell diseasept_PT
dc.subjectPharmacological interventionpt_PT
dc.subjectChildrenpt_PT
dc.subjectAdolescentpt_PT
dc.titleComparative efficacy and safety of pharmacological interventions for sickle cell disease in children and adolescents: a network meta-analysispt_PT
dc.typeconference object
dspace.entity.typePublication
oaire.citation.endPage46pt_PT
oaire.citation.issueS1pt_PT
oaire.citation.startPage46pt_PT
oaire.citation.titleHemaSpherept_PT
oaire.citation.volume7pt_PT
person.familyNameTonin
person.familyNameHonrado Ginete
person.familyNameNeves Delgadinho
person.familyNameBrito
person.givenNameFernanda
person.givenNameAna Catarina
person.givenNameMariana Isabel
person.givenNameMiguel
person.identifierCAJ-5082-2022
person.identifier.ciencia-idD01C-C700-9411
person.identifier.ciencia-id8715-F62E-1E0F
person.identifier.ciencia-id231E-02E3-D9A9
person.identifier.ciencia-id231F-F341-7E93
person.identifier.orcid0000-0003-4262-8608
person.identifier.orcid0000-0002-2334-782X
person.identifier.orcid0000-0003-0586-9154
person.identifier.orcid0000-0001-6394-658X
person.identifier.ridO-2050-2017
person.identifier.ridA-7970-2016
person.identifier.scopus-author-id56085115800
person.identifier.scopus-author-id35224551000
rcaap.rightsopenAccesspt_PT
rcaap.typeconferenceObjectpt_PT
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relation.isAuthorOfPublicationdfb2fbba-17ff-42fb-905a-fcfc8f326e1c
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relation.isAuthorOfPublication.latestForDiscoverydfb2fbba-17ff-42fb-905a-fcfc8f326e1c

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