Efficacy And Safety Of Rituximab For Patients With Immune Thrombocytopenia:A Systematic Review And Meta-analysis

Objective:Rituximab(RTX),one of the second-line treatments for pediatric immune thrombocytopenia(ITP),has relatively definite efficacy in adult with ITP.In recent years,some reports of clinical research on the efficacy and safety of ITP in children have been published,but the overall number of cases is relatively small,and there is no meta-analysis on the RTX treatment in children with ITP.The study aimed to evaluate the efficacy and safety of RTX in children with ITP by systematic review and meta-analysis,thus providing more reliable evidence of evidence-based medicine for the further application and its status.Methods:Two independent researchers searched CNKI,Wanfang Database,CBM,VIP Database,PubMed,OVID&EMBASE,Web of science,Clinical Trials.gov and Cochrane Library respectively and independently.Search terms include:"Purpura,Thrombocytopenic,Idiopathic",immune thrombocytopenia,ITP,idiopathic thrombocytopenia,autoimmune thrombocytopenia,primary thrombocytopenia,rituximab、"CD20 antibody and rituximab",adolescent、child,"child,preschool"、infant、age before 18 and thrombocytopenia.From the establishment of each database to November 2019,eligible researches on RTX treatment in children with ITP were obtained.Analysis indexes include:overall response(OR),complete response(CR),relapse and adverse events(AEs).The meta-analysis was performed using Stata software(version 15.0).Random effects models and fixed effect models were used to pool outcomes across studies.Sensitivity analysis was performed to determine if the results would be different.Results:Among the 3457 articles we retrieved,1083 duplicate articles were removed;101 animal experiments or reviews that are obviously not related to the research contents were deleted,and the rest articles were kept for primary screen.After reading the title and abstract of the literature,2124 articles that are inconsistent with the research content were excluded,and the rest were downloaded.The references were excluded according to the inclusion criteria(all prospective clinical trials of rituximab treatment in children with ITP;children aged from 1 month to under 19 years old;English or Chinese data)and exclusion criteria(the number of cases was less than 10;full text could not be obtained;retrospective study).By reading the full text carefully,139 articles did not meet the standard of this study.In the end,10 studies met the inclusion criteria of meta-analysis.Among them,there were 3 qualified references in the low-dose rituximab group,with 92 cases of children with ITP;7 qualified references in the standard dose rituximab group,with 156 cases of children with ITP.OR,CR,relapse rate and adverse events rate were 0.58(95%CI 0.47～0.69,I2=70.4%)、0.37(95%CI 0.28～0.46,I2=50.5%)、0.26(95%CI 0.14～0.38,I2=61.8%)、0.17(95%CI 0.08～0.27,I2=59.6%)respectively.Conclusion:The results of this study show that RTX is an effective second-line treatment drug in children with ITP.However,the long-term efficacy of the drug is still unclear.In the future,large samples of high-quality randomized controlled trials are needed to further evaluate the efficacy and safety of RTX in children with ITP.