Meta-analysis Of Therapeutic Efficacy And Safety Of Oral Propranolol Alone Or Combined With Glucocorticoid In The Treatment Of Infantile Hemangiomas

Background:Beta blockers are mainly used to treat cardiovascular diseases such as arrhythmia,hypertension and angina.In 2008,Leaute-Labrèze et al used propranolol in the treatment of 2 children with heart disease with hemangioma.It was discovered by chance that propranolol could inhibit the growth of hemangioma.Since then,propranolol were used in the treatment of hemangioma,and gradually became the first-line therapeutic drug^[1].Hemangioma can be classified into infantile hemangiomas?IHs?,congenital hemangioma and Kasabach-Merritt syndrome according to the latest classification methods,among which infantile hemangiomas is the most common.A large number of retrospective studies and clinical trials have shown that propranolol is effective and safe in the treatment of infantile hemangiomas.In addition,drug combination and laser combination therapy have also begun to be popular.Some studies have pointed out that propranolol combined with glucocorticoid has made achievements in curing or relieving infantile hemangiomas^[2],but the efficacy and safety of the propranolol alone or combined with glucocorticoid has yet to be systematically evaluated.Objective:To systematically evaluate the therapeutic efficacy and safety of propranolol alone or combined with glucocorticoid in the treatment of infantile hemangiomas.Methods:Data sources:We searched Randomized controlled trials?RCTs?from the PubMed,Cochrane Library,Web of Science,CNKI and VIP databases for studies which are published before September 2018.There were no language restrictions.Inclusion and Exclusion Criteria:Include conditions:Randomized controlled trials?RCTs?of propranolol alone or in combination with glucocorticoids in the treatment of infantile hemangiomas;The lesion were limited to the skin of children.Exclude conditions:Data of retrospective analysis and case reports were screened out;Visceral hemangiomas?such as the liver?,choroidal hemangiomas,intraspinal hemangiomas and other special types of hemangiomas?PHACE syndrome etc.?were excluded.Quality evaluation of the included literature:The Cochrane Collaboration's tool for assessing risk of bias was used,and the literature with high risk bias was screened out.Data extraction and Analysis:Two reviewers independently extracted data and discussed to solve the conflicts.For the included literature,Rev Man 5.0 software was used for meta-analysis.If p>0.10 and I²<50%,it was considered that the included literature were not heterogeneous,and the fixed effect model was used for relative risk?RR?and 95%CI to calculate the total effect amount of the data;If p?0.10,it was considered that there was heterogeneity in the included literature,and the random effect model can be used to calculate the total statistic.X² test standard was set at 0.05.Finally,a funnel plot was used for publication bias assessment.Results:A total of 431 related studies were retrieved from this study,and 12 randomized controlled trials were included,totaling 685 children.Meta-analysis shows that for infantile hemangiomas,the efficacy and safety of oral propranolol were statistically different from glucocorticoid[Efficacy:RR=1.48,95%CI?1.29,1.70?,p<0.05;Safety:RR=0.18,95%CI?0.11,0.28?,p<0.05];The efficacy of propranolol combined with glucocorticoid was statistically different from oral propranolol alone[RR=1.27,95%CI?1.04,1.56?,P<0.05];To the children younger than 6 months,propranolol combined with glucocorticoid is more effective than propranolol alone[RR=1.32,95%CI?1.05,1.65?,P<0.05],but there was no difference in the children who are elder than 6 months;There was no significant difference in the incidence of adverse reactions between combined therapy and oral propranolol alone.Conclusions:1.For infantile hemangiomas?IHs?,oral propranolol is more effective and safer than glucocorticoid.2.For IHs of children who are younger than 6 months,oral propranolol combined with glucocorticoid is better than oral propranolol alone,but for IHs of children who are elder than 6 months,there is no difference between the two methods mentioned above.3.For IHs,oral propranolol combined with glucocorticoids does not cause increased adverse reactions,which means that oral propranolol combined with glucocorticoids is safe in treating IHs.