Indirect Comparison Of Efficacy And Safety Of Topiramate And Atogepant In Migraine Prophylaxis

Objective:By comparing topiramate and Atogepant,a new oral drug,to understand whether there are differences in the efficacy and safety of the two in the preventive treatment of migraine.Due to the lack of head-to-head clinical trials of topiramate versus Atogepant,a systematic review and meta-analysis of the efficacy and safety of topiramate versus Atogepant in the prophylactic treatment of migraine will be conducted by indirect comparison.It is hoped that the results of this study will provide reference for the choice of medication for the prophylactic treatment of migraine.Methods:Two researchers independently searched Pub Med,Embase and The Cochrane Library to collect randomized controlled trials(RCT)of topiramate and Atogepant prophylactic treatment for migraine.The search time is from the establishment of each database to February 2023.Keywords included migraine,preventive therapy,prophylaxis,topiramate,Atogepant,etc.The risk of bias of included studies were assessed by using the Cochrane assessment tool.Efficacy was evaluated using changes in mean monthly migraine days from baseline,treatment response rate,and the change in monthly days of acute medication use from baseline.Safety was evaluated using total adverse event incidence and withdrawal rate.Rev Man 5.4 was used to complete a meta-analysis comparing topiramate/Atogepant directly with placebo and a heterogeneity test of studys.Indirect treatment comparison(ITC)software was used to calculate the efficacy and safety results between topiramate and Atogepant,and Stata 14 software was used to evaluate the publication bias.Results:A total of 1294 literatures were obtained by searching various databases,and 10 literatures were included for meta-analysis and systematic review after strict screening,including three drugs,topiramate,Atogepant and placebo,involving 4097 subjects,including 3348 females and 749 males.For migraine subjects receiving prophylactic therapy,in terms of efficacy,topiramate was better than placebo in the change in the mean monthly migraine days from baseline [MD=-1.34,95%CI(-1.80,-0.88),P < 0.00001],treatment response rate [RR=2.07,95%CI(1.78,2.41),P < 0.00001] and the change in monthly days of acute medication use from baseline [MD=-0.92,95%CI(-1.40,-0.44),P < 0.00001].In terms of safety,topiramate was higher than placebo in the total adverse reaction rate[RR=1.98,95%CI(1.37,2.87),P < 0.0003] and withdrawal rate [RR=2.04,95%CI(1.58,2.62),P < 0.00001].In terms of efficacy,Atogepant was better than placebo in the change in the mean monthly migraine days from baseline [MD=-1.18,95%CI(-1.40,-0.96),P <0.00001],treatment response rate [RR= 1.60,95%CI(1.39,1.84),P < 0.00001] and change in monthly days of acute medication use from baseline [MD=-1.33,95%CI(-1.54,-1.12),P< 0.00001].In terms of safety,there was no significant difference in the total adverse reaction rate of Atogepant versus placebo [RR=1.10,95%CI(0.99,1.22),P=0.09],and the rate of withdrawal with Atogepant was higher than placebo [RR=1.52,95%CI(1.02,2.25),P=0.04].The ITC indirect comparison results showed that,for preventive treatment of migraine,the change in the mean monthly migraine days from baseline [MD=-0.16,95%CI(-0.67,0.35),P=0.90] and treatment response rate [RR=1.29,95%CI(1.05,1.59),P=1.00] of topiramate were higher than Atogepant in terms of efficacy,but the difference was not statistically significant.Topiramate was less effective than Atogepant in monthly days of acute medication use from baseline [MD=0.41,95%CI(-0.11,0.93),P=0.80],but the difference was not statistically significant.In terms of drug safety,the total adverse reaction rate [RR=1.80,95%CI(1.23,2.64),P=0.99] and withdrawal rate [RR=1.34,95%CI(0.84,2.15),P=0.20] of topirate were higher than Atogepant,with no statistically significant difference.Conclusion:Both Atogepant and first-line topiramate showed significant efficacy in the prophylactic treatment of migraine,and Atogepant was effective at 10 mg,30mg and 60 mg doses.The adverse event rate of Atogepant was comparable to placebo.The prophylactic treatment of migraine with Atogepant may be safer than topiramate.