Migraine is a prevalent neurological disease around the globe. However, previous therapies have some limitations or adverse effects, and are unresolved until now. As the importance of CGRP in the pathogenesis has been proved by the previous studies, its receptors are widely distributed in the central nervous system (CNS) and peripheral sensory neurons. Therefore, monoclonal antibodies blocking the CGRP ligand or receptor have a clear advantage in the treatment strategy for episodic and chronic migraine[15].
Our study is the first meta-analysis about different dosage regimens related to the safety and efficacy of eptinezumab in the treatment for migraine, and indicated eptinezumab as excellent therapeutic agent for the migraine. During our study, we pooled 2,739 participators from 4 randomized clinical trials (RCTs), which provided high clinical reliability in the research for the use of eptinezumab. Further, we gathered primary data from those articles and did not discover apparent heterogeneity in our outcomes as indicated by our statistical analysis. Subsequently, we found that eptinezumab had been divided into flexible dosage regimens in these RCTs, including 10 mg, 30 mg, 100 mg, 300 mg, 1000 mg. Further, by comparing the primary efficacy outcomes mean monthly migraine days (MMDs), baseline to 12 week, we proved that treatment with 30 mg, 100 mg, 300 mg can cause effective reduction in monthly migraine days (MMDs) compared with placebo. Whereas, for the secondary endpoint, all dosage regimens of eptinezumab increased the proportion of 75% responder rate except 10 mg. Similar results were observed in 50% responder rate. In addition, fewer patients suffered from migraine 1 day after 100 mg and 300 mg eptinezumab administration compared with 30 mg. Due to the lack of research and subsequent data, we could not continue further exploration of 10 mg (only in the study conducted by Dodick et al 2014) and 1000 mg (only in the study conducted by Dodick et al 2019) for the efficacy of eptinezumab. However, it doesn’t mean that these dosage regimens were insignificant, probably research related to it needs more time for comprehensive outcome.
By analyzing the results of different dosage regimens of eptinezumab, we found that the dosage regimens of 100 mg and 300 mg were more significant in the efficacy of the treatment for migraine. Therefore, further study was carried out for these two dosage regimens. From the perspective of the outcome related to the MMDs, baseline to 12 week, 300 mg(P = 0.06) eptinezumab showed no significant difference but potential tendency for the reduction of MMDs compared with 100 mg. Nevertheless, for the 75% responder rate, 300 mg eptinezumab has been proved more increasing proportion than 100 mg. The result of 50% responder rate and patients with migraine 1 day after dosing couldn’t indicate the difference between 100 mg and 300 mg. Nonetheless, we can conclude that the dosage regimen of 300 mg has an advantage on the efficacy of the treatment for migraine.
During our study, the analysis of safety outcomes—TEAEs did not indicate existence of statistical difference between eptinezumab and placebo (P > 0.05). Therefore, generally the use of eptinezumab is safe for the treatment of migraine. The result was consistent with the meta-analysis conducted by Da Xu and Deng Chen [16] which demonstrated monoclonal antibodies blocking the CGRP ligand or receptor are safe. As reported in the previous studies, we observed that eptinezumab rarely causes serious adverse events or even death [17, 18]. Moreover, it only resulted in some mild adverse events such as upper respiratory tract infection, nausea and sinus congestion, just like the other monoclonal antibodies blocking the CGRP ligand or receptor[19]. Certainly, these studies on adverse events merely evaluated 12 weeks after the first dose. We cannot ensure whether eptinezumab will produce long lasting influence. Therefore, it still needs further comprehensive research.
After the analysis of our data, we found few limitations in our study which cannot be avoided through existing researches. First, numerous previous studies have concluded evidence to use other CGRP monoclonal antibodies such as ubrogepant, galcanezumab and rimegepant, for the treatment of migraine [20–22]. However, as interventions in our study were related to different dosage regimens of eptinezumab and placebo, we can only conclude the advantages of eptinezumab compared with placebo. Probably, our study needs more horizontal comparison of eptinezumab with other CGRP monoclonal antibodies in the future. Secondly, considering different dosage regimens in 4 RCTs, 1000 mg eptinezumab merely conducted by Dodick 2014, whereas, 10 mg merely conducted by Dodick 2019. Moreover, part of statistics from Dodick 2019, Ashina 2020 and Lipton 2020 did not indicate standard deviation (SD) clearly. However, in the present study, we ultimately achieved SD using statistical algorithm on our own. Therefore, the accuracy of the results needs further verification. Except for the limitation above, we also cannot ignore the lack of adherence in the therapy of migraine which occurred in our 4 RCTs in a way. This also encountered by few traditional treatments for migraine [23, 24].