Terapia antiadesão para crise vaso-oclusiva em doença falciforme : revisão sistemática

• Ano de defesa: 2017
• Autor(a) principal: Silva, Adriano Morita Fernandes da [UNIFESP]
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de São Paulo (UNIFESP)
• Palavras-chave em Português: Anemia, sickle cell; Acute pain; Endothelium; Cell adhesion; Therapy; Systematic review; Anemia falciforme; Dor aguda; Endotélio; Adesão celular; Terapia; Revisão sistemática
• Link de acesso: https://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=5632817; http://repositorio.unifesp.br/handle/11600/50395

Objective: To evaluate the efficacy and safety of anti-adhesion agents in the management of painful crises in patients with sickle cell disease. Methods: Systematic review and meta-analysis of randomized controlled trials according to the Cochrane methodology. Participants: individuals with sickle cell disease. Intervention: the following anti-adhesion therapies were considered for inclusion of the study - rivipansel, crizanlizumab, propranolol, poloxamer, pentosan polysulfate sodium, glycosylation inhibitors, anti-p-selectin aptamers and MEK inhibitors. Comparison: standard treatment, placebo or no treatment. Outcomes: rate of painful crisis, duration of the crisis in hospitalized patients, pain intensity, opioid consumption, biomarkers of endothelial activation and adverse effects. Results: We found four studies with a total of 584 participants (children and adults of both sexes) who tested the active drug compared to placebo. Three studies (rivipansel phase II and poloxamer phase II and III) evaluated the effect of the medication as an abortive treatment of the painful crisis. The study poloxamer phase II was described only in a narrative way since the results provided did not allow to perform meta-analysis. This study (high risk of bias) reported a significant reduction in the pain score for the poloxamer arm, but there was no significant difference in the duration of the crisis and opioid use. On the other hand, the studies rivipansel phase II and poloxamer phase III (low risk of bias for both) were combined in meta-analysis. Regarding the duration of the crisis and the intensity of pain, the meta-analysis between the two studies did not show a significant difference between the intervention and placebo groups. At last, the study crizanlizumab tested the drug for prevention of painful crises. This study (198 participants) was considered as low risk of bias, and showed that the annual rate of painful crisis was significant lower (reduction of 62.9%) in the high-dose crizanlizumab group compared to placebo. None of the included studies evaluated the biomarkers of endothelial activation. Adverse effects were, in general, similar between active drugs and placebo groups. Conclusion: Current evidence is insufficient to recommend anti-adhesion agents for manage painful crisis of individuals with sickle cell disease.