Efficacy and Safety of Calcitonin Gene-related Peptide Monoclonal Antibodies in the Preventive Treatment of Migraine：A Bayesian Network Meta-analysis / 中国药房

OBJECTIVE：To systematically evaluate th e efficacy and safety of 4 kinds of calcitonin gene-related peptide （CGRP）monoclonal antibodies in the preventive treatment of migraine ，and to provide evidence-based reference for the clinical treatment of migraine. METHODS ：Retrieved from the Cochrane Library ，PubMed，Embase，CJFD，VIP and Wanfang database ， RCTs about 4 kinds of CGRP monoclonal antibodies （trial Δ 基金项目 ：四川省科技厅重点研发 （重大科技专项 ）项目 group） versus placebo （control group ） in the preventive （No.2019YFS0180） ＊硕士研究生 。研究方向 ：临床药学 、循证药学 。电话：0830- treatment of migraine were collected. After literature screening 3165787。E-mail：lewxinn@outlook.com and data extraction ， the quality evaluation of included # 通信作者：教授，硕士生导师，硕士。研究方向：临床药学、循证 literature was performed by using the bias risk assessment tool 药学。电话：0830-3165787。E-mail：hyl3160131@163.com provided by the Cochrane system evaluator manual 5.1.0. 中国药房 2020年第31卷第18期 China Pharmacy 2020Vol. 31 No. 18 ·2275· Bayesian network Meta-analysis was performed by using GeMTC 0.14.3 software and Stata 16.0 software. RESULTS ：A total of 19 RCTs involving 11 392 patients were included ，involving 10 interventions，such as Erenumab 70，140 mg/month；Fremanezumab 675 mg/3 months，225 mg/month；Galcanezumab 120，240，300 mg/month；Eptinezumab 100 mg/3 months，300 mg/3 months and placebo. Results of Meta-analysis showed that compared with control group ，4 kinds of CGRP monoclonal antibodies significantly reduced the change of mean monthly migraine days （MMD）（P＜0.05）. Among trial groups ，compared with Galcanezumab 300 mg/month [MD ＝－1.30，95％CI（－2.59，－0.05），P＜0.05] and Eptinezumab 100 mg/3 months [MD ＝－1.18， 95％CI（－2.26，－0.03），P＜0.05]，Fremanezumab 225 mg/month could significantly reduce MMD. Network Meta-analysis ranking showed that Fremanezumab 225 mg/month＞Fremanezumab 675 mg/3 months＞Galcanezumab 120 mg/month＞Erenumab 140 mg/month＞Galcanezumab 240 mg/month＞Eptinezumab 300 mg/3 months＞Erenumab 70 mg/month＞Eptinezumab 100 mg/3 months＞Galcanezumab 300 mg/month＞placebo. Compared with control group ，4 kinds of CGRP monoclonal antibodies were significantly increased of the proportion of patients whose mean monthly migraine days reduction ≥50％ compared with baseline （MMD 50）（P＜0.05）. Among trial groups ，compared with Eptinezumab 100 mg/3 months group ，MMD 50 of Fremanezumab 675 mg/3 months group [OR ＝1.51，95％CI（1.02，2.31），P＜0.05]，Fremanezumab 225 mg/month group [OR ＝1.58，95％CI （1.05，2.44），P＜0.05] were increased significantly. Network Meta-analysis ranking showed that Fremanezumab 225 mg/month＞ Fremanezumab 675 mg/3 months＞Erenumab 140 mg/month＞Galcanezumab 120 mg/month＞Eptinezumab 300 mg/3 months＞ Galcanezumab 240 mg/month＞Erenumab 70 mg/month＞Galcanezumab 300 mg/month＞Eptinezumab 100 mg/3 months＞placebo. In terms of safety ，incidence of total adverse events （AE）of trial groups receiving Fremanezumab 675 mg/3 months [OR ＝1.31， 95％CI（1.05，1.64），P＜0.05]，Galcanezumab 240 mg/month [OR ＝1.39，95％CI（1.09，1.74），P＜0.05] were significantly higher than control group. Among trial groups ，compared with Galcanezumab 240 mg/month group ，AE of Erenumab 70 mg/month group [OR ＝0.67，95％CI（0.50，0.93），P＜0.05]，Erenumab 140 mg/month group [OR ＝0.70，95％CI（0.51，0.98），P＜0.05] were decreased significantly. Compared with Fremanezumab 675 mg/3 months group ，AE of Erenumab 70 mg/month group [OR ＝ 0.72，95％CI（0.52，0.98），P＜0.05] were decreased significantly. Network Meta-analysis ranking showed that Galcanezumab 240 mg/month＞ Fremanezumab 675 mg/3 months＞Galcanezumab 120 mg/month＞Galcanezumab 300 mg/month＞Eptinezumab 300 mg/3 months＞Fremanezumab 225 mg/month＞Eptinezumab 100 mg/3 months＞placebo＞Erenumab 140 mg/month＞Erenumab 70 mg/month. CONCLUSIONS ：Four kinds of CGRP monoclonal antibodies are effective in the preventive treatment of migraine ， among which Fremanezumab 225 mg/month is most likely to have the best efficacy and Erenumab 70 mg/month is most likely to have the highest safety.

Efficacy and Safety of Ubrogepant and Rimegepant in the Treatment of Acute Migraine ：A Meta-analysis / 中国药房

OBJECTIVE：To systemat ically evaluate the efficacy and safety of Ubrogepant and Rimegepant in the treatment of acute migraine ，and to provide evidence-based reference for the clinical treatment. METHODS ：Retrieved from PubMed ，Embase， Cochrane Library ，CNKI，VIP，Wanfang database and Clinicaltrials. gov ，randomized controlled trials （RCTs） about the Ubrogepant and Rimegepant （trial group ）versus placebo （control group ）in the treatment of acute migraine were collected during the inception to Jan. 2020. After literature screening and data extraction ，quality assessment was performed using the bias risk assessment tool provided by the Cochrane system evaluator manual 5.1.0. Meta-analysis was performed by using Stata 16.0 software. RESULTS ：Eight RCTs with a total of 7 989 patients were included. The results of Meta-analysis showed that the proportion of patients who were free from pain at 2 h postdose in Ubrogepant group [RR ＝1.65，95％CI（1.38，1.98），P＜0.001] and Rimegepant group [RR ＝1.69，95％CI（1.46，1.95），P＜0.001]，the proportion of patients who were free from the most bothersome symptom at 2 h postdose in Ubrogepant group [RR ＝1.35，95％ CI（1.20，1.53），P＜0.001] and Rimegepant group [RR ＝1.37，95％CI（1.24，1.51），P＜0.001]，and other secondary outcome indicators （ i.e. the proportion of patients with pain relief at 2 h postdose ，the proportion of patients with sustained freedom from pain from 2-24 h postdose ，the proportion of patients with sustained pain relief from 2-24 h postdose ，the proportion of patients without photophobia at 2 h postdose ，the proportion of patients without phonophobia at 2 h postdose ，the proportion of patients without nausea at 2 h postdose ）were all significantly better than control group （P＜0.05）. In terms of safety ，there was no statistical significance in the incidence of total ADR between Ubrogepant group and control group [RR ＝1.04，95％CI（0.87，1.25），P＝0.646]，but the incidence of total ADR in Rimegepant group were significantly higher than control group [RR ＝1.23，95％ CI（1.01，1.50），P＝0.043]. There was no statistical significance in other security indicators （i.e. incidence of nausea ，dizziness，dry mouth ，somnolence，urinary tract infection）in 2 groups（P＞0.05）. CONCLUSIONS ：Ubrogepant and Rimegepant are effective in the treatment of acute migraine. Ubrogepant is safe ，while Rimegepant may increase the incidence of ADR.