Search results
Sixty-nine studies and abstracts were retrieved from MEDLINE and Embase, as well as 42 studies from the Cochrane Library and clinicaltrials.gov. 73 studies were removed owing to duplication, and 7 studies were eliminated because they were not directly related to the topic, such as studies of other drugs or pathophysiological study of migraine. After removing duplicates and irrelevant articles, 31 articles were directly related to the topic of interest. However, 28 of these articles were excluded because there were 1 conference, 2 protocol, 4 post-hoc analysis studies, 6 unfinished RCTs, 1 meta-analysis (Interventions are not atogepant versus placebo), 8 comments and 6 reviews. Eventually, 3 RCTs were included in our study and related information was shown in supplementary materials S1. The complete search process was detailed in the Fig. 1.
Primary efficacy outcomes
After measurement, we considered one metric in this study as primary outcomes, namely monthly migraine days (Fig. 2). In terms of this, each of the different doses of atogepant group showed a certain amount of advantages. The mean monthly migraine days during 3 months in the atogepant 10 mg group was 0.41 days less than the days in the placebo group (SMD = − 0.41, 95%CI: [− 0.56, − 0.25], P < 0.00001), the atogepant 30 mg group (SMD = − 0.41, 95%CI: [− 0.55, − 0.27], P < 0.00001) and the atogepant 60 mg group (SMD = − 0.42, 95% CI: [− 0.73, − 0.11], P = 0.007) as well.
Secondary efficacy outcomes
In this part, a number of endpoint measures were also estimated to explore the efficacy of atogepant for migraine, including monthly headache days, acute medication use days per month and ≥ 50% reduction in monthly migraine days (Fig. 3, 4 and 5). It revealed that the mean monthly headache days in the atogepant 10 mg (SMD = − 0.43, 95%CI: [− 0.59, − 0.28], P < 0.00001), 30 mg (SMD = − 0.42, 95%CI: [− 0.60, − 0.24], P < 0.00001), 60 mg once-daily groups (SMD = − 0.41, 95%CI: [− 0.73, − 0.10], P = 0.01) were all less than the days in the placebo group. Moreover, the decrease in the average number of days of medication use monthly in 3 months was also an indication of the change in the number of days of migraine attacks and thus confirmed the preventive effect of the drugs. Specific results were as follows: the atogepant 10 mg group (SMD = − 0.45, 95%CI: [− 0.61, − 0.30], P < 0.00001), the atogepant 30 mg group (SMD = − 0.49, 95%CI: [− 0.63, − 0.35], P < 0.00001), the atogepant 60 mg group (SMD = − 0.46, 95%CI: [− 0.60, − 0.32], P < 0.00001). In regard to the outcomes of ≥ 50% reduction in monthly migraine days, the proportion of patients in the atogepant 10 mg group with a 50% or more reduction in mean migraine days per month during 3 months had a pronounced increase than the placebo group (RR = 1.66, 95%CI: [1.23, 2.23], P = 0.0008), after that, the same was true for the atogepant 30 mg group (RR = 1.63, 95%CI: [1.07, 2.49], P = 0.02) and the atogepant 60 mg group (RR = 1.64, 95%CI: [1.01, 2.66], P = 0.04).
Safety outcomes
Since the types of adverse events could not be discriminated clearly, only the total number of adverse events was analyzed. As a result, there were no significant differences in outcomes of adverse events between the treatment groups and the placebo group. (atogepant 10 mg: RR = 1.11, 95%CI: [0.78, 1.56], P = 0.57, atogepant 30 mg: RR = 1.08, 95%CI: [0.79, 1.48], P = 0.64, atogepant 60 mg: RR = 0.96, 95%CI: [0.79, 1.17], P = 0.68, Fig. 6).
Subgroup analysis
We separately conducted a comparative analysis of atogepant 10 mg and 30 mg, 10 mg and 60 mg, 30 mg and 60 mg about their efficacy (monthly migraine days, monthly headache days and monthly medication use days) and safety. The results showed that none of the differences in present outcomes (all p > 0.05) (Shown in supplement materials S2 and S3).
Risk of bias
The independent risk of bias of the three included trials has been appraised with details of Fig. 7. The risks for blinding of outcome assessment (detection bias) are all unclear in the Goadsby et al. 2020 study, Allergan et al. 2021 and Ailani et al. 2021 study. Study conducted by Allergan et al. 2021 had three additional biases that were unclear because the details of the relevant research were not yet available. In addition to the above mentioned, other risks were all low risks of bias in the three trials.