Consistency of response to rimegepant for the acute treatment of migraine among real-world users – findings from the prospective observational CONFIDENCE study

Abstract

Background

Real-world data on the effectiveness of rimegepant for the acute treatment of migraine is limited, particularly regarding consistency of response over multiple attacks.

Methods

CONFIDENCE was a prospective observational survey study with screening and baseline questionnaires; a 28-day observational period where participants completed daily assessments on migraine occurrence, treatment, and outcomes; and an end of study questionnaire. Adults in the United States with 3–14 headache days in the last 30 days, a rimegepant prescription for the acute treatment of migraine, and plans to use rimegepant in the next 30 days were recruited in phases via the Migraine Buddy® app; firstly, those with/without preventive therapies, and then, those taking specific preventive therapies. A primary outcome of CONFIDENCE was consistency of rimegepant response across multiple attacks at the population and participant levels regardless of preventive migraine therapy. Positive treatment outcomes were defined as (1) meaningful pain relief (MPR) within 2 hours, (2) meaningful improvement in function (MIF) within 2 hours, and (3) attacks where participants reported being ‘satisfied’ or ‘extremely satisfied’ with rimegepant (treatment satisfaction).

Results

416 participants recorded data for 2169 rimegepant-treated migraine attacks (median: 7/participant). Participants’ mean age was 40 years, 91% were female, 90% were White, and 84% took ≥ 1 preventive therapy. At baseline, participants reported a median (IQR) of 8 (5, 10) headache days/month and 40% had very severe migraine-related disability as measured by the Migraine Disability Assessment score ≥ 41. Among all rimegepant-treated migraine attacks recorded in the study, 61% achieved MPR and 58% achieved MIF within 2 hours, while 68% achieved treatment satisfaction. Of the 349 participants who treated ≥ 3 attacks, favorable outcomes were achieved in ≥ 2 of their first 3 recorded attacks for MPR within 2 hours in 65%, MIF within 2 hours in 60%, and treatment satisfaction in 74%. 55%, 48%, and 66% of participants achieved these outcomes in ≥ 3 of their first 4 attacks (n = 289 participants with ≥4 attacks).

Conclusions

Consistently positive treatment outcomes were observed at the population (all attacks) and participant levels in this real-world observational study of > 400 participants and >2000 migraine attacks treated with rimegepant.

Trial registration

NCT06467370

Introduction

The most important attributes of acute migraine therapy include efficacy, tolerability, and consistency of response [1]. Although efficacy and tolerability are routinely assessed in clinical trials, consistency of response is less frequently evaluated [2]. Consistency can be used to refer to several distinct aspects of acute migraine therapy. It can refer to the efficacy across subgroups of patients defined by characteristics such as age, biological sex, race, ethnicity, or comorbidities. In this context, consistent treatment is one with similar effect across subgroups. Consistency at the population level can also describe the change in efficacy across multiple uses, as measured by the proportion of patients achieving a specified endpoint in sequential attacks. Consistency can also be evaluated at the patient level (within patient) to describe the proportion of treated attacks that respond to treatment.

For patients, a treatment that provides reliable effectiveness brings predictability to their lives. Knowing they will be able to quickly return to planned activities should a migraine attack occur provides benefits both at the time of an attack and between attacks. This often leads to higher treatment satisfaction and longer persistence on treatment [3]. Confidence in acute migraine treatment has been associated with better social functioning, improved mental health, and an overall higher quality of life [4]. Within patient consistency translates into having treatment that can be relied on to work every time it is used. Medications with consistently positive outcomes reduce the need to overuse or layer medications to ensure effectiveness [5].

Within patient consistency is similarly important for healthcare professionals. It describes how predictable the treatment response will be for a particular patient. Treatments that work in some patients or only on some occasions can be difficult to use in clinical practice. A high level of within patient consistency makes it easier to optimize treatment and reduces the number of healthcare visits required to manage migraine [1, 6, 7].

At a broader level, consistent treatment outcomes contribute to meaningful societal benefits. Treatments with consistent effectiveness provide both direct cost savings e.g. reduced need to seek medical attention, and indirect cost savings, e.g., lower rates of unemployment/educational disruption, and reductions in disability-related societal costs. Consistency also supports health technology assessments and economic modeling by reducing the uncertainty around real-world effectiveness. In the 2020 guidance on the Health Technology Assessment for the Acute Treatment of Migraine Attacks and Prevention of Migraine, the International Headache Society identified reliability across migraine attacks as an important benefit of acute treatment [8]. This built on the 2019 Guidelines for Controlled Trials of Drugs in Migraine that recommended consistency of response is evaluated in randomized controlled trials over ≥ 4 or more attacks [2]. As most randomized controlled trials conducted to date have evaluated efficacy in a single attack and were not designed to evaluate consistency across multiple attacks, this is an area where real-world observational studies can provide additional insight [9].

Gepants are a newer class of small molecules specifically designed to treat or prevent migraine attacks by antagonizing the receptor for calcitonin gene-related peptide (CGRP) [10–12]. Rimegepant is currently the only gepant approved as both an acute and preventive treatment for migraine [13, 14]. CONFIDENCE was a study specifically designed to better understand the effectiveness of rimegepant for the acute treatment of migraine over multiple attacks in the real world. The primary aim of CONFIDENCE was to evaluate the consistency of rimegepant response regardless of concomitant preventive migraine therapy. This was examined in terms of the achievement of meaningful pain relief, meaningful improvement in function, and treatment satisfaction at both the population level (all attacks, and in the first, second, third, and fourth attacks reported by each participant) and participant level (response in ≥ 2 of 3 and ≥3 of 4 first reported attacks).

Methods

Study design

CONFIDENCE (A prospeCtive ObservatioNal study with acute treatment oF rImegepant orally Disintegrating tablet on consistENcy, satisfaCtion and tolerability of trEatment in the real world) was a prospective real-world observational survey study (NCT06467370; registration date: 21 June 2024) that recruited participants located in the United States via the Migraine Buddy® app (https://migrainebuddy.com) [15]. Participants were directed to a bespoke module to complete the study. Migraine Buddy® is a smartphone app used to track migraine triggers, symptoms, and treatments by over 3.5 million people globally and >1,300,000 from the United States [15]. The app has been used to recruit cohorts for several large observational studies of people with migraine and represents an important source of real-world data [16–23]. In a validation study, it was determined that > 90% of the enrolled samples met the International Classification of Headache Disorders 3^rd edition criteria for migraine [18].

A brief depiction of the study stages is shown in Fig. 1. App users in the United States who had taken rimegepant for the acute treatment of migraine were considered potentially eligible and invited to participate via message or in-app notification. The link took them to a dedicated study module inside Migraine Buddy®. No further preselection was conducted. The 7-item multiple-choice pre-screening questionnaire assessed the key inclusion and exclusion criteria: age ≥ 18 years, current rimegepant prescription for the acute treatment of migraine, plans to use rimegepant in this context within the next 30 days, ≥3 migraine attacks in the last 30 days, not taking rimegepant for the prevention of migraine, did not have a diagnosis of cluster headache, post-traumatic headache, new daily persistent headache, hemicrania continua, or chronic daily headache, and was not taking part in a migraine-related clinical trial. Those who qualified and agreed to take part in the study were immediately invited to take the screening questionnaire. This asked about any current preventive treatments using up to 16 multiple-choice items. To allow an inclusive study population reflecting real-world users of rimegepant, stable preventive use was permitted. Future subgroup analyses to assess the effects on rimegepant in patients taking onabotulinumtoxinA or CGRP monoclonal antibody (mAb) are planned. Participants with concurrent onabotuliumtoxinA and CGRP mAb use were excluded because of difficulty in assigning to either treatment group. We considered combination treatment would be too rare to generate a group large enough for separate analysis. People on oral preventive therapy were required to have been on stable doses for the past 3 months. For monthly preventive therapies, the person must have received a dose within the last 3 weeks. For quarterly preventive therapies, the person must have received a dose within the last 2 months. Respondents were also asked how many headache days they had in last 30 days (free-text entry). Those with between 3 and 14 headache days were eligible to enroll.

Fig. 1.

Study design. MIDAS = Migraine Disability Assessment; mTOQ = migraine Treatment Optimization Questionnaire; Rx = prescription; TSQM = Treatment Satisfaction Questionnaire for Medication

The CONFIDENCE study aimed to enroll up to 468 participants, including 75 without current preventive therapy, 71 with other current oral preventive therapy (only), 156 with current CGRP mAb preventive therapy (with or without oral preventive therapy), and 156 with current onabotulinumtoxinA preventive therapy (with or without oral preventive therapy). Enrollment was conducted in phases. Initial open enrollment of eligible people was conducted until a total of 75 participants without current preventive therapy were included. Subsequent enrollment targeted those with specific preventive therapy backgrounds until the quota above were met. Using quota sampling, once enrollment into a subgroup was complete, there could be no further recruitment into that group, even if a person met the other eligibility criteria. Several future analyses are planned from CONFIDENCE. These enrollment targets were set pragmatically, based on estimated subgroup sizes required for future analyses and study practicalities. Given an expected dropout rate of 20%, it was expected that 335 to 374 participants would complete the study.

Those eligible to join the study after completing the screening questionnaires were invited to complete a 20-item multiple-choice and free-text entry baseline questionnaire with honorarium. The baseline questionnaire collected demographic and clinical data for each participant. This included further details of their use of over-the-counter and prescription pain medications, current and past triptan use, date of first ever rimegepant use for the acute treatment of migraine, and Migraine Disability Assessment (MIDAS) score. The MIDAS is a validated questionnaire to assess migraine-related disability in terms of impact on daily activities over the prior 3 months. [24] In this study, MIDAS scores were classified as follows: 0–5 little or no disability; 6–10 mild disability; 11–20 moderate disability; 21–40 severe disability; ≥41 very severe disability.

The 28-day observation period began the day after baseline questionnaire completion. Each participant was sent daily diary questions at 8 pm. Questions were available for 72 hours to maximize data collection while limiting the influence of recall bias. If the participant reported taking rimegepant within 4 hours of receiving the daily questions they were prompted to return the following morning at 8am to complete the entry for the previous day. The daily questionnaire asked participants if they had experienced a migraine attack that day. If ‘yes,’ up to 21 further multiple-choice questions requested details of the attack, the acute treatments used, and the outcomes (including time to meaningful pain relief, meaningful improvement in function, and assessments of treatment satisfaction). During the study, participants were free to select any acute treatment of migraine available to them. No study medication was provided.

After 28 days of observation, participants were invited to complete an end of study questionnaire comprising up to 20 multiple-choice items to receive an honorarium. Those who had previously submitted all 28 consecutive daily diary entries were provided an additional honorarium. The end of study questionnaire collected information about whether the participant currently had periods (menstruation), along with migraine Treatment Optimization Questionnaire version 6 (mTOQ-6) and Treatment Satisfaction Questionnaire for Medication version II (TSQM-II) surveys that focused on the use of rimegepant for the acute treatment of migraine [25–27].

The protocol and all relevant documents were prospectively approved by the Advarra Institutional Review Board (Pro00079359). The study was conducted in accordance with all legal and regulatory requirements, and according to good practice guidelines in relation to pharmacoepidemiologic research. All participants provided informed consent during screening.

Measures

Three treatment outcomes were assessed for each rimegepant-treated migraine attack recorded in the Migraine Buddy® daily diary:

1. Achievement of meaningful pain relief within 2 hours of treatment. This was sourced from the daily diary question: “After taking Nurtec today/on [day], how long did it take for you to first experience meaningful relief of your headache pain? Meaningful relief means your pain was reduced to a level that makes a meaningful difference for you, even if pain was not completely gone.” Note that Nurtec is the brand name for rimegepant in the United States. The multiple-choice answers were: less than 1 hour; more than 1 hour up to 2 hours; more than 2 hours up to 4 hours; more than 4 hours; or did not experience meaningful relief. The outcome focuses on the proportion of participants who selected ‘less than 1 hour,’ or ‘more than 1 hour up to 2 hours’ (pooled).

2. Achievement of meaningful improvement in function within 2 hours of treatment. This was sourced from the daily diary question: “After taking Nurtec, when did you experience a meaningful improvement in functioning?” The multiple-choice answers were as above for pain relief. The outcome focuses on the proportion of participants who selected ‘less than 1 hour,’ or ‘more than 1 hour up to 2 hours’ (pooled). In the context of the questionnaire flow, we assumed participants’ interpretation of ‘functioning’ to be their ability to perform daily activities.

3. Being ‘satisfied’ or ‘extremely satisfied’ with rimegepant treatment of the migraine attack. This was sourced from the daily dairy question: “Overall, how satisfied are you with Nurtec for treating your migraine attack?” The multiple-choice answers were: extremely satisfied; satisfied; slightly satisfied; neither satisfied nor dissatisfied; slightly dissatisfied; dissatisfied; or extremely dissatisfied. The outcome focused on the proportion of participants who selected ‘satisfied’ or ‘extremely satisfied’ (pooled).

All responses reflected the subjective perceptions of participants. Further reasoning for each response was not captured.

Analyses

Consistency of response to rimegepant was assessed at both the population (all attacks) and participant levels. All analyses were planned to be descriptive and were based on available data. Participants were included in the analyses if they had data for ≥21/28 daily questionnaires in the observation period and an end of study questionnaire.

At the population level, the achievement of each outcome (achievement of meaningful pain relief within 2 hours of rimegepant treatment; achievement of meaningful improvement in function within 2 hours of rimegepant treatment; and attacks where the participant reported being ‘satisfied’ or ‘extremely satisfied’ with rimegepant treatment) was assessed in all recorded rimegepant-treated attacks. No controls were added to account for within-person correlations. These outcomes were also individually assessed in each first, second, third, and fourth rimegepant-treated migraine attack reported by each participant in the study. Similar outcomes have been used in other studies that recruited through the Migraine Buddy® app [19–22].

At the participant level, the proportion of participants achieving each of the outcomes in ≥ 2 of their first 3, or ≥ 3 of their first 4 rimegepant-treated attacks recorded in the study were assessed. These analyses build on previous research on triptans, including the European Headache Federation definition of a triptan-responder (effective treatment in ≥ 3 of 4 consecutive attacks) [1, 28–30]. Similar analyses have been used in other observational studies evaluating acute migraine treatments [31–33].

Results

The CONFIDENCE study was conducted between July 2024 and March 2025. Of the 1673 people contacted and 467 who completed the screening questionnaires, 466 enrolled in the study, completed the baseline questionnaire, and entered the 28-day observation period. Of these, 440 completed the end of study questionnaire; 429 of these had ≥ 21 daily diary entries. A total of 416 participants completed the end of study questionnaire with ≥21 daily diary entries and full reporting for ≥1 rimegepant-treated migraine attack (Fig. 2). Together, these 416 participants reported complete data for 2169 rimegepant-treated migraine attacks (median of 7 attacks per participant [quartile (Q)1, 3: 5, 10]).

Fig. 2.

Participant selection and study completion

The first stage of enrollment was completed in August 2024 with a total of 207 participants. The proportion of participants with each preventive migraine medication use is shown in Fig. 3A. The 209 participants enrolled after this date were specifically selected to be current users of oral preventive therapy (only), CGRP mAb preventive therapy, or onabotulinumtoxinA preventive therapy. The final analysis population of 416 participants reporting ≥ 1 rimegepant-treated migraine attack was therefore artificially enriched, particularly with participants who used onabotulinumtoxinA preventive therapy. (Fig. 3B).

Fig. 3.

Use of preventive medication at the end of the initial open enrollment phase and in the final analysis population following selective enrollment. CGRP mAb = calcitonin gene-related peptide monoclonal antibody

Participant demographics and clinical characteristics

Among the 416 participants reporting ≥ 1 rimegepant-treated migraine attack during the study, mean age was 39.6 years, 90.9% were female sex at birth, and 90.4% reported they were White (Table 1). Though 84.1% took preventive migraine treatments, the median number of headache days per month at study entry was 8; 54.6% reported having an average of 8 to 14 headache days per month (14 being the upper limit for study eligibility; Figs. 3, 4). Mean body mass index (BMI) was 30 kg/m² with 44.2% classified as obese (BMI ≥ 30 kg/m²). Overall, 40.4% of participants had a MIDAS score ≥ 41, indicating very severe migraine-related disability. In total, 88.9% (n = 370) of participants reported that they had taken and then discontinued (lapsed) ≥1 triptan for the acute treatment of migraine prior to baseline, including 31.7% (n = 132) who had lapsed 1 triptan, 32.2% (n = 134) who had lapsed 2 triptans, and 25.0% (n = 104) who had lapsed ≥ 3 triptans. A minority of participants (28.4%; n = 118) were current triptan users. Median time since the start of rimegepant use for the acute treatment of migraine was 458 days (i.e., 1.25 years; Q1, Q3: 169, 844 days).

Table 1.

Demographics at baseline

	Participants with ≥1 rimegepant-treated migraine attacks N = 416
Age, mean (SD), years	39.6 (10.9)
Sex assigned at birth, n (%)
Female	378 (90.9)
Male	38 (9.1)
Ethnicity and race, n (%)a
Hispanic or Latino	30 (7.2)
White	376 (90.4)
Black or African American	19 (4.6)
Asian or Asian American	10 (2.4)
American Indian or Alaska Native	9 (2.2)
Native Hawaiian or Other Pacific Islander	1 (0.2)
Other	1 (0.2)
Prefer not to answer	1 (0.2)
Participants who reported having periods (menstruation), n (%)	230 (55.3)
Health insurance, n (%)
Commercial	329 (79.1)
Medicare	26 (6.3)
Medicaid Managed Care	23 (5.5)
Federal	21 (5.0)
Exchanges	12 (2.9)
Medicaid Fee for Service	3 (0.7)
Cash	2 (0.5)

^aFindings from a single question where participants could select > 1 answer

Fig. 4.

Clinical characteristics at baseline. BMI = body mass index; CGRP mAb = calcitonin gene-related peptide monoclonal antibody; MIDAS = Migraine Disability Assessment; Q = quartile; SD = standard deviation

Consistency of rimegepant response at the population level (all attacks)

Among all 2169 rimegepant-treated migraine attacks reported in the study, 61.3% (95% CI: 59.2, 63.3) achieved meaningful pain relief within 2 hours of treatment, 57.6% (95% CI: 55.5, 59.7) achieved meaningful improvement in function within 2 hours of treatment, and 68.4% (95% CI: 66.4, 70.3) were attacks where participants reported being ‘satisfied’ or ‘extremely satisfied’ with rimegepant treatment (Fig. 5). These analyses report raw percentages that are not adjusted for within-person correlations. Similar proportions of first, second, third, and fourth rimegepant-treated migraine attacks reported during the study achieved these outcomes (Fig. 5).

Fig. 5.

Consistency of response at the population level. h = hours; RIM = rimegepant

Consistency of rimegepant response at the participant level (within participants)

Of the 349 participants who reported ≥ 3 rimegepant-treated migraine attacks, favorable outcomes were achieved in ≥ 2 of their first 3 attacks for meaningful pain relief within 2 hours in 65.0% (95% CI: 60.0, 70.0), meaningful improvement in function within 2 hours in 59.6% (95% CI: 54.5, 64.7), and being ‘satisfied’ or ‘extremely satisfied’ with rimegepant treatment in 73.9% (95% CI: 69.3, 78.5; Fig. 6). Of the 289 participants who reported ≥ 4 rimegepant-treated migraine attacks during the study, favorable outcomes were achieved in ≥ 3 of their first 4 attacks for meaningful pain relief within 2 hours in 54.7% (95% CI: 48.9, 60.3), meaningful improvement in function within 2 hours in 48.4% (95% CI: 42.7, 54.2), and being ‘satisfied’ or ‘extremely satisfied’ with rimegepant treatment in 65.7% (95% CI: 60.1, 71.0).

Fig. 6.

Consistency of response within participants. h = hours; RIM = rimegepant

Discussion

CONFIDENCE was a large prospective observational survey study undertaken in participants who routinely used rimegepant for the acute treatment of migraine. The study found consistently positive participant-reported treatment outcomes over multiple attacks in the real-world, both at the population level (all attacks) and participant level (in ≥ 2 of 3 and ≥3 of 4 treated attacks).

In all first rimegepant-treated attacks reported in the study by each participant, 65% achieved meaningful pain relief within 2 hours of treatment, 59% achieved meaningful functional improvement within 2 hours of treatment, and 72% achieved overall satisfaction with rimegepant treatment of the attack. These proportions were very similar over participant’s second, third, and fourth rimegepant-treated attacks (61–64%, 58%, and 69–71%, respectively), and among all 2169 rimegepant-treated attacks reported in the study (61%, 58%, and 68%, respectively). These findings show a high degree of consistency of response to rimegepant at the population level. A similarly high level of consistency was seen at the participant level, where 60% to 74% of participants reported achievement of each outcome in ≥ 2 of their first 3 rimegepant-treated attacks reported in the study. These proportions were only slightly lower (48% to 66%) when assessed over ≥ 3 of participants’ first 4 rimegepant-treated attacks. Together, these findings show around two-thirds of patients who take rimegepant in the real-world experience positive treatment outcomes, and this effectiveness is consistent over multiple attacks.

Although CONFIDENCE offers the largest prospective evaluation of real-world rimegepant to date, consistency findings are supported by previous smaller studies [34, 35]. In a study using data from the US Adelphi Disease Specific Programme™, physicians reported that 73% of patients with migraine achieved pain freedom within 2 hours of rimegepant intake in >50% of treated attacks, and 76% of patients reported pain freedom within 2 hours of rimegepant intake in ≥ 4 of 5 attacks [34]. Further, 95% of physicians and 97% of patients were satisfied with rimegepant treatment [34]. In an open-label multicenter pilot study of patients with chronic or episodic migraine in Greece, levels of pain reduction 2 hours after rimegepant treatment were similar in the first and all recorded attacks (n = 54 and n = 140, respectively) [35]. Although cohorts are not directly comparable, a high degree of consistency has also been reported with another gepant, ubrogepant, in clinical trial and real-world observational studies across multiple attacks, including in participants taking preventive therapy [20–22, 36, 37].

Consistency of response to acute migraine medication is important to patients, healthcare professionals, healthcare systems, and society [6]. Migraine is a common and debilitating condition associated with significant disability among working-age people [38]. A high degree of consistency allows patients and healthcare professionals to confidently predict future treatment responses. This is valuable in determining regimen optimization, achieving treatment satisfaction, and reducing the need to seek further healthcare assistance [1, 3, 5–7]. Patients with consistently well-controlled migraine attacks have a better quality of life and are more able to participate in work, education, and daily activities [3, 4]. This is of benefit to healthcare systems and society more broadly, and a high degree of outcome consistency supports more accurate economic modeling and determination of real-world therapeutic value [8].

Findings from CONFIDENCE demonstrate the effectiveness of rimegepant during experienced use. CONFIDENCE enrollment was conducted in phases, with the latter targeting recruitment of those with oral, CGRP mAb, or onabotulinumtoxinA preventive therapy. This created an enriched final analysis population where the proportion and types of preventive therapies used were no longer representative of the real-world population. Although 84% of participants took preventive therapy, 55% reported 8 to 14 headache days per month and 40% had very severe migraine-related disability on MIDAS. Due to the high number of breakthrough attacks with considerable burden, this suggests the analysis population may represent a population with relatively treatment refractory migraine. Despite this, the pain relief findings were broadly comparable to those in phase 2/3 randomized clinical trials where rimegepant was used to treat a single migraine attack of moderate or severe pain severity in treatment-naïve populations with less severe disease (56% to 79% at 2 hours) [39–45].

Limitations

Results should be considered in the context of the enrolled population; namely participants who routinely choose to use rimegepant for the acute treatment of migraine, often in addition to preventive medication, and with frequent and disabling breakthrough attacks. This likely selected for participants who respond well to rimegepant and tolerate it. This limitation could be addressed in future studies by enrolling participants just starting on rimegepant, though such eligibility criteria can greatly complicate enrollment and study logistics. Analyses presented are descriptive and did not control for within-person correlation among participants who contributed multiple attacks. Another limitation is the lack of placebo or active comparator with which to assess the relative real-world effectiveness of rimegepant. This means we cannot assess whether rimegepant is more effective than placebo or other approved acute treatments for migraine in the real-world. The study also lacked specific questions asking about tolerability. This element is partially captured in the satisfaction outcome. Inherent to all survey studies, responses provided by participants were potentially influenced by bias, both conscious and unconscious. We collected data on a daily basis, but the potential for recall bias remains. Typically, clinical trials collect data in real-time prior to treatment and at fixed intervals after treatment. Collecting data at multiple time points would increase participant burden and perhaps reduce study participation. Throughout the study, participants were free to treat their condition as they wished. This included changes to preventive medication and choice of acute medication/s for each attack. We did not control these factors as meticulously as in controlled trials. In this real-world study, we elected to prioritize rapid enrollment and to minimize participant burden. We believe these choices served our objective well. Limitations are in the context of the large study size and evaluation of real-life rimegepant use, which are key strengths.

Conclusions

Findings from CONFIDENCE demonstrate consistent achievement of meaningful pain relief, meaningful improvement in function, and overall satisfaction outcomes across multiple attacks among > 400 real-world users of rimegepant for the acute treatment of migraine.

Abbreviations

BMI

Body mass index

CGRP

Calcitonin gene-related peptide

CONFIDENCE

A prospeCtive ObservatioNal study with acute treatment oF rImegepant orally Disintegrating tablet on consistENcy satisfaCtion and tolerability of trEatment in the real world

mAb

Monoclonal antibody

MIF

Meaningful improvement in function

MIDAS

Migraine disability Assessment

MPR

Meaningful pain relief

mTOQ6

migraine Treatment Optimization Questionnaire version 6

Q1/Q3

First/third quartile

TSQM-II

Treatment Satisfaction Questionnaire for Medication version II

Author contributions

RBL: conception and design of the work, analysis and interpretation of the data, substantial revision of the manuscript AU: conception and design of the work, analysis and interpretation of the data, substantial revision of the manuscript GL: analysis and interpretation of the data, substantial revision of the manuscript PJG: analysis and interpretation of the data, substantial revision of the manuscript PP-R: analysis and interpretation of the data, substantial revision of the manuscript TJS: analysis and interpretation of the data, substantial revision of the manuscript KMF: conception and design of the work, analysis and interpretation of the data, substantial revision of the manuscript LA, FD, KHB: conception and design of the work, analysis and interpretation of the data, All authors read and approved the final manuscript.

Funding

This study was sponsored by Pfizer.

Data availability

Upon request, and subject to review, Pfizer will provide the data that support the findings of this study. Subject to certain criteria, conditions, and exceptions, Pfizer may also provide access to the related individual de-identified participant data. See https://www.pfizer.com/science/clinical-trials/trial-data-and-results for more information.

Declarations

Ethics approval and consent to participate

The protocol and all relevant documents were prospectively approved by an Institutional Review Board (Advarra, Pro00079359). The study was conducted in accordance with all legal and regulatory requirements, and according to good practice guidelines in relation to pharmacoepidemiologic research. All participants provided informed consent.

Consent for publication

N/A

Competing interests

RBL: Editorial board of Neurology and senior advisor to Headache (not paid); research support: NIH and FDA; support from the National Headache Foundation; research grants, consultant, advisory board member or honoraria: Aeon, Allergan/AbbVie, Amgen, Axsome, Dr Reddy’s Laboratories, Eli Lilly, GSK, Ipsen, Lundbeck, Pfizer, Merck, Teva, Vedanta; royalties from Informa and Wolff’s Headache (8th edition, Oxford University Press, 2009); stock options in Biohaven Pharmaceuticals, CoolTech, Manistee, and NuVieBio. AU: Employee of Aptar Digital Health, which was a paid consultant to Pfizer for the conduct of this study. GL: Consulting fees: AbbVie, Dr Reddy’s Laboratories, Eli Lilly, Lundbeck, Pfizer, and Teva. PJG: Consulting fees: Aeon, AbbVie, CoolTech, Dr Reddy’s Laboratories, Eli Lilly, Epalex, Ipsen, Kallyope, Linpharma, Lundbeck, Orion Pharma, Pfizer, PureTech Health, Satsuma, Seaport Therapeutics, Shiratronics, Teva; personal fees for advice: Gerson Lehrman Group, Guidepoint, SAI Med Partners, Vector Psychometric; fees for educational materials: CME Outfitters and WebMD; publishing royalties or fees: Massachusetts Medical Society, Oxford University Press, UptoDate, and Wolters Kluwer. PP-R: In the last 3 years, consultant and speaker: AbbVie, Almirall, Dr. Reddy’s, Eli Lilly, Lundbeck, Medscape, Novartis, Organon, Otsuka Pharmaceuticals, Pfizer, Teva; research grants to her research group: AbbVie, AGAUR, EraNet Neuron, FEDER RIS3CAT, Instituto Investigación Carlos III, MICINN, Novartis, Teva; funding for clinical trials: AbbVie, Amgen, Eli Lilly, Lundbeck, Merz, Pfizer, Teva; associate editor for Cephalalgia, NS Neurologia; member of the Clinical Trials Guidelines Committee and Scientific Committee of the International Headache Society; edited Guidelines for the Diagnosis and Treatment of Headache of the Spanish Neurological Society; founder of http://www.midolordecabeza.org, a platform to give information and tools to physicians and people who suffer from migraine and other headaches. TJS: In the last 24 months served as a consultant for AbbVie, Lundbeck, and Salvia, received royalties from UpToDate, had research support from AbbVie, American Heart Association, Flinn Foundation, Henry Jackson Foundation, National Headache Foundation, National Institutes of Health, Patient Centered Outcomes Research Institute, Pfizer, and US Department of Defense, and had stock options/equity in Allevalux and Nocira. KMF: Managing director of MIST Research, which has received research funding from AbbVie, Allay Lamp, NYC Langone Health, Juva Health, Migraine Canada, AESARA, and Aptar. LA, FD, KHB: Employees of and own stock/options in Pfizer.