Data sources
Data for this analysis were extracted from a systematic literature review (see Figure 1 and Appendix S1 ). In brief, electronic databases including Embase, MEDLINE, and the Cochrane Library were searched for randomised, controlled trials of migraine-preventive treatments from inception to June 2021. Additional grey literature searching encompassed 2020–2021 headache/migraine congresses, the ClinicalTrials.gov website, and several Health Technology Assessment websites. Only clinical studies in humans, published in English language, were selected. While the literature review was not fully comprehensive, it was judged to be sufficiently complete for the purposes of informing the current analysis. In addition, data on file from the DELIVER trial (which was not yet published at the time of conducting the analysis) was used to supplement the data identified by the SLR.
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We included data from published, placebo-controlled trials for anti-CGRPs (18 articles detailing 14 studies) conducted in patients with either episodic or chronic migraine . Where available, phase 3 or phase 4 randomised, controlled trials with a double-blind period of at least 12 weeks’ duration were identified. If such studies were unavailable for any anti-CGRP, data from phase 2 randomised, controlled studies were used instead. For this analysis, only data from the placebo arm of each included trial were evaluated. For a few phase 3, anti-CGRP therapeutic trials (ARISE, PROMISE-1, and PROMISE-2), the percentage of patients who had failed ≥2 prior preventive migraine treatments could not be identified in the literature; thus assumptions were made. The phase 3 ARISE study of erenumab 70 mg vs placebo in patients with episodic migraine reported only the percentage of patients who had failed 1 or more prior treatment (n=115/291, 39.5%) ; however, as this was comparable with that reported in another phase 3 study of erenumab in episodic migraine (STRIVE; n=127/391, 39.8%), it was assumed that the percentage of patients who had failed ≥2 treatments in ARISE was the same as the percentage in STRIVE. For the phase 3 studies of eptinezumab (PROMISE-1 in episodic migraine ; PROMISE-2 in chronic migraine ), the percentages of patients with ≥2 treatment failures were not captured in the case report form; thus, it was assumed that there were no patients with ≥2 treatment failures in either study. The potential implications of this assumption are presented in the Discussion section. Informed consent and Institutional Review Board approval were not applicable for this publication.