Eltrombopague para adultos e crianças com púrpura trombocitopênica imune refratária: uma revisão sistemática

Abstract

Introduction: Eltrombopag is an agonist that binds to the trans-membrane domain of the thrombopoietin receptor (TPO), resulting in signaling through the JAK/STAT, AKT and MAPK pathways, similar to the TPO signaling mechanism. Objective: To evaluate the efficacy and safety of Eltrombopag in adults and children with refractory Immune Thrombocytopenic Purpura (ITP). Methods: This study was a systematic review of randomized clinical trials investigating the efficacy and safety of Eltrombopag in adults and children with refractory ITP. Searches were performed in six electronic databases from inception to May 5, 2021. Two independent reviewers selected studies, extracted data, and assessed the risk of bias of included studies. Meta-analyses were calculated using random effect models to obtain Risk Ratio and their respective 95% confidence intervals. The assessment of the overall quality of evidence was assessed using the Grades of Recommendation, Assessment, Development and Evaluation (GRADE). Results: Nine studies were considered eligible for this systematic review, 7 studies included adults and 2 included children. The meta-analysis demonstrated that adults who received Eltrombopag were more likely to have a platelet response (7 studies, n=759; RR 3.65; 95% CI: 2.39, 5.55), with no difference between groups for the occurrence of bleeding (6 studies; n = 736. RR 0.8; 95% CI: 0.52, 1.22) or adverse events (5 studies, n=527; RR 0.99, 95% CI: 0.55, 1.78). Regarding children, the meta-analysis revealed no difference between Eltrombopag and placebo for platelet response above 50,000 (2 studies, n=159; RR 3.93, 95% CI: 0.56, 27.79) and number of adverse events (2 studies; n=159; RR 0.99; 95% CI: 0.25, 1.49); there was a difference between the groups for the occurrence of bleeding, which was greater in the placebo group (2 studies; n=159; RR 0.47; 95% CI: 0.27, 0.83). Conclusion: Eltrombopag proved to be effective, with a better platelet response, lower incidence of bleeding, and no difference in adverse events when compared to placebo. However, in children, despite the lower incidence of bleeding observed, more robust studies are needed.