Abstract: Background: There are few clinical studies on the efficacy and safety of exon 51 skipping therapy for Duchenne muscular dystrophy(DMD)，and the efficacy and safety are not clear. Objective: To systematically evaluate the efficacy and safety of exon 51 skipping therapies for DMD. Design: Systematic review and meta-analysis. Methods: PubMed, Embase, The Cochrane Library, clinicaltrials.gov, CBM, CNKI, WanFang Data and VIP databases were electronically searched to collect RCTs related to exon 51 skipping Eteplirsen, Drisapersen, Suvodirsen and SRP-5051 for DMD. The retrieval period was from the establishment of the database to October 21, 2021. The risk of bias assessment tool for RCT recommended by the Cochrane Handbook was used to evaluate the the included literature. Then meta-analysis was performed using RevMan 5.3 software. Main outcome measures: Changes in 6-minute walk test (6MWT) and North Star Ambulatory Assessment (NSAA) scores from baseline to 24 weeks after treatment. Results: A total of 5 RCTs involving 322 DMD children were included, investigating Eteplirsen in one study and Drisapersen in 4 studies. As for literature risk of bias evaluation, the specific method of randomization and whether allocation concealment was implemented were not explained in one literature about Eteplirsen. Except for one study that did not blind the evaluator of outcome, all the other studies were blind to the study object, the study implementor and the study evaluator, and the risk of implementation bias and measurement bias was low. All 5 RCTs were registered with no missing data, so the risk of loss of follow-up bias and reporting bias were low. The results of meta-analysis showed that there were no significant differences in changes in 6MWT(MD=-9.16, 95%CI: -21.94~3.62, P=0.16) and NSAA scores (MD=1.20, 95%CI: -2.35~4.75, P=0.51) between the treated group and placebo group. Incidence of renal toxicity （29.0% vs 16.0%, RR=2.2, 95%CI:1.2~4.0, P=0.01）and injection site reactions （52.4% vs 12.0%, RR=7.4, 95%CI:3.4~15.7,P<0.001） in the Drisapersen group was higher than that in placebo group, and the difference was statistically significant. Conclusion: The therapeutic effect of exon 51 skipping on DMD at 24 week is not significant, and there may be side effects such as renal toxicity and injection site reactions.

Key words: Duchenne muscular dystrophy, Eteplirsen, Drisapersen, Randomized controlled trial, Meta-analysis