Although several controlled clinical trials have established the efficacy and safety of eptinezumab [17,18,19,20,21], this study examined the effectiveness and satisfaction of eptinezumab in a real-world clinical setting of 94 patients with CM from multiple headache centers in the United States. In contrast to the participant populations in the eptinezumab clinical trials, this study included a broader range of patients with comorbidities, and patients with prior exposure to newer migraine-specific preventive therapies, including anti-CGRP mAbs, onabotulinumtoxinA, and gepants, thus more accurately reflecting current real-world patient characteristics.

Data from this study indicate that, despite prior exposure to various preventive therapies, patients self-reported a positive impact on a variety of domains after initiating eptinezumab treatment. Moreover, patients reported a higher degree of confidence in their overall well-being. Remarkably, this study demonstrated that patients experiencing continued migraine burden who had previously tried other anti-CGRP mAb preventive treatments responded positively to eptinezumab; this suggests empirically that exposure and trial of one anti-CGRP mAb does not necessarily preclude a positive response to eptinezumab treatment. Recent studies also corroborate this finding [22,23,24,25], with one study showing that patients with previous exposure to erenumab or galcanezumab who subsequently initiated eptinezumab treatment had an overall reduction in monthly migraine days of ∼ 8.4 and ∼ 8.2, respectively, over a 6-month period [22]. These findings have implications for public health and best practices for clinicians navigating through treatment decisions among a variety of advanced migraine therapies. They substantiate the existence of human-to-human variability in responsiveness to anti-CGRP mAbs. They also suggest that general policies from payors and government health plans at both local and national levels, which dictate the selection of some treatments while not offering others, are not fully supported by the most current evidence [26].

Patients reported that their number of monthly “good” days doubled after commencing eptinezumab treatment. This is important, as the definition of “good days” was defined by the individual patient. Additionally, this outcome measure shifts the focus to a patient feeling well compared to other measures which solely focus on when a patient feels poorly. These findings underscore a substantial improvement in patients’ perception of overall well-being through eptinezumab treatment. This is especially noteworthy in a subpopulation with a history of trying several preventive therapies for CM. Illness perception has been demonstrated to influence factors such as chronicity, quality of life, treatment adherence, and psychosocial responses in various diseases, including those with a high burden of headache. In the case of CM, this connection is particularly relevant, as it correlates with a lower quality of life. Therefore, this self-reported measure suggests that positively influencing illness perception in CM may serve as a proxy for improved quality of life and reducing the burden of the disease.

Patients experiencing a high frequency of monthly migraine days often rely on frequent use of acute headache medication, which can lead to medication overuse [27,28,29]. Acute medication overuse is associated with many negative outcomes, including the risk of migraine chronification (progression from episodic migraine to chronic migraine) and medication-overuse headache [30]. In this study, patients, supported by the physicians’ report, reported a decrease in the use of acute migraine medications after initiating treatment with eptinezumab.

It is well known that migraine symptoms can vary from attack to attack and across individual patients. In this study, patients treated with eptinezumab reported high satisfaction with its ability to impact migraine symptomology. Offering patients a therapeutic option that effectively addresses their individualized symptoms can improve adherence, reduce or prevent the frequent use of acute medication, and ultimately lead to higher patient satisfaction.

Migraine-related comorbidities and burden can significantly affect various aspects of a patient’s life [31]. As a result, it is valuable to assess the disease-related burden beyond the impacts of migraine symptoms alone. In this study, questions were posed to explore theses effects on daily living. After initiating eptinezumab, patients reported higher satisfaction with elements of daily living, such as planning life and participation in social/family life and overall well-being. No treatment-related change and/or no worsening was observed in domains, including energy levels, sleep quality, and anxiety/stress levels. Patients may have comorbidities or social determinants of health that can affect these aspects of overall well-being, and these factors may be independent of the specific impact on migraine burden.

Brain fog, often associated with migraine, can have a debilitating impact on cognition and may occur during or between migraine attacks [32, 33]. The ability of migraine-specific therapies to improve brain fog has rarely been studied in clinical trials [18, 19, 34,35,36]. In this population of patients with CM, 80% had reported experiencing brain fog (i.e., feeling confused, difficulty learning or remembering, or trouble speaking or reading), indicating the pervasiveness of this symptom in this population. Remarkably, of the patients who said they had experienced brain fog, a large majority (86%) reported that they experienced some level of improvement in their brain fog after initiating eptinezumab treatment. To date, research evaluating the impact of preventive treatments on cognition are limited, with focus on traditional oral therapies and onabotulinumtoxinA [37]. These findings suggest that further research is needed to fully understand cognitive burden and the impact of preventive therapies.

A previous patient preference study evaluated attributes of non-oral preventive migraine medications that are most important to individuals with migraine. It was shown that individuals preferred a treatment with a quick speed of onset that lasted for its full treatment duration. Additionally, the previous study showed that while preference for the mode of administration varied between people, 75% of individuals did not think intravenous infusion was a barrier to care [38]. The REVIEW study corroborates the previous patient preference study results in that while 62% of patients indicated being at least slightly concerned about infusion before receiving eptinezumab, this number decreased to 14% following treatment. This indicates that a majority of patients experienced an improved acceptance of infusion as a route of administration. Moreover, almost all patients (94%) who received eptinezumab agreed that it was convenient to receive treatment via an infusion.

Before beginning a new treatment, patients can establish treatment goals either independently or in collaboration with their clinicians. The process of setting treatment goals represents a form of shared decision-making, facilitating better understanding of patients’ individual health needs and treatment preferences. This, in turn, leads to the development of personalized treatment plans. This study identified three categories of treatment goals: those related to symptom resolution, treatment approaches, and overall quality of life. Notably, only 59% of patients in this survey reported setting goals with their physicians. Therefore, ensuring alignment of treatment expectations between patients and prescribing physicians may be an area in need of improvement. Despite not all patients explicitly reporting the creation of treatment goals in collaboration with their physicians, 52% of the surveyed patients with CM affirmed that they successfully achieved their treatment goals while on eptinezumab, reflecting real-life improvements in their personal treatment objectives.

Patient data were survey-based and self-reported, thus dependent upon patient recall. Moreover, 51% of respondents reported receiving five or more infusions, which further impacts recall, but may reflect a patient population that has continued therapy due to positive response and/or good tolerability. One patient reported only receiving one infusion of eptinezumab; however, it was confirmed by investigators that all included patients had received at least two infusions. Gepants captured included atogepant, ubrogepant, and rimegepant; given the nature of our methodology, however, differentiation between preventive use versus acute use for rimegepant was not possible. In addition, concomitant use of therapies in conjunction with eptinezumab was not deciphered within the patient charts or patient survey. Moreover, it was not determined why patients switched therapies; it could be due to tolerability, efficacy, and/or payor-related reasons. No cross-comparisons were conducted among the outcome measures for the 100-mg, 200-mg, or 300-mg doses, and ad hoc analyses were not performed for patients transitioning between lower and higher doses. Further exploration of the specific reasoning and considerations for the 200-mg, an off-label eptinezumab dose, was not conducted. The final survey was provided to the patient with no additional guidance/interpretation; however, a linguistic assessment was performed in 10 patients to optimize survey questions prior to the start of the study. Patient diary data were unavailable, which limited further corroboration of effectiveness on a continual log basis, as opposed to cross-sectional patient recall. Moreover, inherent selection bias in this study could not be mitigated.