Rimegepant for migraine prevention in clinical practice: A multicenter study including patients with prior anti-CGRP monoclonal antibody failure (GEMA project)

Abstract

Background

Rimegepant is a calcitonin gene-related peptide (CGRP) receptor antagonist approved for both acute and preventive treatment of episodic migraine. Real-world data on its preventive use remain limited, particularly in patients with multiple prior preventive failures. This study evaluated the effectiveness and tolerability of rimegepant in routine clinical practice, focusing on a highly treatment-resistant population.

Methods

We conducted a prospective, multicenter real-world cohort study within the GEMA (GEpants in MigrAine) Project across nine tertiary Headache Units in Spain. Adults initiating rimegepant for migraine prevention were consecutively enrolled and followed for up to 6 months. The primary endpoint was the 3-month change in monthly headache days (MHD). Secondary endpoints included the change in monthly migraine days (MMD), response rates, predictors of response, and tolerability. Baseline characteristics, prior preventive failures, medication overuse, adverse events, and patient-reported outcomes (Headache Impact Test-6 (HIT-6), HADS, and Insomnia Severity Index) were recorded.

Results

In total, 150 patients completed 3-month follow-up and 64 reached 6 months. The cohort was predominantly female (85.3%), with 70.7% episodic migraine, a median age of 48 years (interquartile range (IQR) = 39–57), and a median of 6 prior preventive failures (IQR = 4–8), reflecting high treatment resistance. At 3 months, median MHD decreased from 12 to 7.5 and MMD from 10 to 6 (p < 0.05), with significant improvement in HIT-6. Overall, 36% and 43% achieved ≥ 50% reduction in MHD and MMD, respectively (≥ 75%: 15% and 20%). Among patients with 6-month data, further reductions were observed (MHD, 6 days; MMD, 5 days), with ≥ 50% response rates increasing to 48% and 58%. Clinical responders showed greater improvements in anxiety and depressive symptoms. Medication overuse, chronic migraine, and prior exposure to anti-CGRP monoclonal antibodies and onabotulinumtoxinA were independent predictors of poorer outcomes, with response declining with increasing prior anti-CGRP exposure, although a relevant proportion still achieved meaningful benefit. Rimegepant was well tolerated, with predominantly mild adverse events (nausea 13%, constipation 8%) and low discontinuation (7% at 3 months), and with nausea being the most frequent cause.

Conclusions

Rimegepant showed meaningful preventive effectiveness and good tolerability in routine clinical practice, including in highly treatment-resistant patients with prior anti-CGRP monoclonal antibody exposure. The response was influenced by baseline disease burden and prior treatment exposure. These findings suggest that earlier use of rimegepant in the treatment course may be associated with greater clinical benefit.

Graphical abstract

This is a visual representation of the abstract.

Keywords

CGRP receptor antagonist migraine preventive treatment real-world study rimegepant treatment-resistant migraine

Introduction

The therapeutic landscape of migraine prevention has been substantially transformed by treatments targeting the calcitonin gene-related peptide (CGRP) pathway. Following the introduction of monoclonal antibodies directed against the CGRP ligand or receptor, small-molecule CGRP receptor antagonists, known as gepants, have expanded therapeutic options by offering an orally administered, mechanism-based approach acting on the same biological pathway.

Rimegepant, a second-generation gepant, is approved for both the acute and preventive treatment of episodic migraine. Administered as a 75 mg orally disintegrating tablet, its pharmacokinetic profile enables every-other-day dosing for prevention. In the pivotal phase II/III randomized trial, rimegepant significantly reduced monthly migraine days (MMD) compared with placebo, with low discontinuation rates and a favorable tolerability profile.¹ Sustained benefit without emerging safety concerns was confirmed in a 52-week open-label extension,² and additional analyses supported its safety when used concomitantly with other preventive therapies.³ Comparable efficacy and tolerability were also demonstrated in a randomized, double-blind, placebo-controlled trial conducted in a Japanese population.⁴

Narrative syntheses and health utility analyses have further supported its dual acute and preventive efficacy, favorable safety profile, and clinically meaningful improvements in patient-reported outcomes.^5,6 Post-marketing data have not identified clinically significant hepatotoxicity, with only rare and transient aminotransferase elevations reported.⁷

More recently, the phase IV randomized, double-blind, placebo-controlled BHV3000-407 trial evaluated rimegepant in patients with episodic migraine and inadequate response to two to four prior categories of traditional oral preventive medications. In this clinically complex population, rimegepant achieved a significantly greater reduction in MMD compared with placebo, with consistent benefits across secondary endpoints and a safety profile comparable to placebo.⁸ In line with these findings, recent consensus recommendations from the International Headache Society support the use of rimegepant as a preventive option in patients with prior treatment failures, including those with previous exposure to CGRP-targeted therapies, highlighting its role within an evolving treatment algorithm.⁹

Although randomized trials have established its efficacy and safety, real-world data on the preventive use of rimegepant remain limited, particularly in patients with multiple prior preventive failures or long-standing disease. Clinical trial populations do not fully reflect the clinical complexity and therapeutic sequencing decisions encountered in routine practice. This unmet need is further highlighted by recent Global Burden of Disease data, which confirm migraine as a leading cause of disability worldwide, supporting the need for effective preventive options in treatment-resistant populations.¹⁰

In Spain, public reimbursement for preventive rimegepant is granted to patients with episodic migraine who have failed at least three conventional oral preventive treatments. According to the European Headache Federation consensus, resistant migraine is defined as failure of at least three adequately administered preventive classes,¹¹ whereas refractory migraine implies failure of all available preventive options, including onabotulinumtoxinA (BoNT-A) and CGRP-targeted therapies. More recent consensus-based definitions and analyses have further refined this distinction, characterizing both conditions as clinically complex entities associated with substantial therapeutic burden and accumulated prior treatment exposure.^12,13 Consequently, patients eligible for rimegepant in this setting frequently represent a highly treatment-experienced population.

In this context, the present multicenter prospective study aims to evaluate the effectiveness and tolerability of rimegepant as preventive therapy in routine clinical practice, with a particular focus on patients with multiple prior preventive failures and a high treatment burden, corresponding to a population with resistant migraine according to current consensus criteria.

Methods

Study design

We performed a prospective, multicenter real-world analytical cohort study within the framework of the GEMA (GEpants in MigrAine) Project, an investigator-initiated collaborative study across 15 tertiary Headache Units in Spain. For the present analysis, only the nine centers where rimegepant was available were included. Adults who initiated oral rimegepant for migraine prevention from June 2024 onward were consecutively enrolled over a 1-year period, until May 2025. Rimegepant was administered at a dose of 75 mg on alternate days, in accordance with routine clinical practice. Outcomes were analyzed at 3 months in all patients with available follow-up and at 6 months in those who had reached that time point.

The primary objective was to evaluate the effectiveness of rimegepant at 3 months in routine clinical practice. Six-month outcomes were assessed as a predefined exploratory extension.

The study followed Strengthening the Reporting of Observational studies in Epidemiology (STROBE) guidelines for observational research.¹⁴ The study design and reporting were aligned with the International Headache Society (IHS) guidelines for real-world evidence studies in migraine.¹⁵ According to these recommendations, the present study corresponds to a prospective multicenter cohort study with structured data collection using validated patient-reported outcome measures, fulfilling criteria for Data Quality Level 1. The study protocol was prospectively defined and approved by the local ethics committee; however, the study was not preregistered in a public registry.

Participants

Eligible patients were adults (≥ 18 years) with a diagnosis of migraine according to International Classification of Headache Disorders, 3rd edition (ICHD-3) criteria¹⁶ and a disease duration of at least 1 year, who initiated rimegepant for preventive treatment in routine clinical practice. Concomitant preventive treatments were allowed, provided that doses remained stable for at least the first 3 months after rimegepant initiation. No specific exclusion criteria regarding comorbid conditions, other chronic pain conditions, or cognitive status were applied, to reflect real-world clinical practice, with treatment decisions left to the discretion of the prescribing physician. Medication overuse was not considered an exclusion criterion.

Treatment resistance was defined according to the European Headache Federation consensus⁹ as failure of at least three classes of preventive medications. Accordingly, all included patients fulfilled criteria for resistant migraine, whereas the diagnosis of refractory migraine could not be established in all cases.

Data collection and variables

Initial and follow-up visits were documented using standardized electronic case report forms specifically designed for this study within the REDCap (i.e. Research Electronic Data Capture) platform.¹⁷ Data were collected by the investigators through structured interviews and medical record review, ensuring consistency and data quality.

Collected variables included sociodemographic characteristics (age, sex, and age at headache onset), diagnosis or migraine type (episodic vs. chronic migraine), number of previously failed preventive treatments and detailed information on each type of failed preventive treatment (including BoNT-A and anti-CGRP monoclonal antibodies (anti-CGRP mAbs): erenumab, fremanezumab, galcanezumab, eptinezumab). To evaluate whether prior exposure to anti-CGRP mAbs influenced the effectiveness of rimegepant, patients were stratified according to previous mAb treatment and according to the number of prior monoclonal antibody therapies (0–4).

Also, number of concomitant preventive treatments at baseline and detailed specification of each type (including BoNT-A), headache intensity (scale 0–10) and presence and type of aura (visual, sensory, aphasic) were collected.

Headache burden (monthly headache days (MHD) and MMD, including subgroups 0–7, 8–14, and > 15 days at baseline). To further characterize the effectiveness of rimegepant treatment, patients were stratified according to their degree of response: mild (≥ 30% to < 50%), good (≥ 50% to < 75%), excellent (≥ 75%), and full remission (100%).

Medication overuse (MO) and adverse events (AEs) were recorded at baseline and at all follow-up visits. MO was defined according to ICHD-3 criteria as the use of acute medications on ≥ 10 days/month for triptans, ergot derivatives, or combination analgesics, or ≥ 15 days/month for simple analgesics or non-steroidal anti-inflammatory drugs, based on patient-reported headache diaries.

Patient-reported outcome measures were systematically collected at baseline and at each follow-up visit (3 and 6 months). Headache-related impact was assessed with the Headache Impact Test-6 (HIT-6, range 36–78, higher scores indicating greater impact).¹⁸ Symptoms of anxiety and depression were measured using the Hospital Anxiety and Depression Scale (HADS),¹⁹ comprising two subscales (HADS-A for anxiety and HADS-D for depression; range 0–21, with higher scores indicating greater symptom severity). Insomnia severity was evaluated with the Insomnia Severity Index (ISI, range 0–28; higher scores indicate more severe insomnia).²⁰ To explore the relationship between changes in these measures and clinical effectiveness, patients were stratified according to treatment response and categorized as responders (≥ 50% reduction in MHD or MMD) or non-responders (< 50%).

Outcomes

The primary effectiveness outcome was the change in MHD from baseline to month 3. Secondary outcomes included: the change in MMD; the proportion of patients achieving ≥ 30%, ≥ 50%, or ≥ 75% reduction in MHD/MMD from baseline; identification of clinical predictors of response; tolerability; and persistence of effectiveness at 6 months in patients with available follow-up data, which were considered exploratory. Baseline values were defined as the month immediately prior to rimegepant initiation. A month was defined as a standardized 30-day period for calculation of MHD and MMD.

Statistical analysis

Continuous variables were summarized as the mean ± SD or median and interquartile range (IQR), depending on data distribution. Categorical variables were described as frequencies and percentages. Normality was assessed using the D’Agostino–Pearson test. Between-group comparisons were performed using the Kruskal–Wallis test for continuous variables and Fisher's exact test or Pearson's chi-squared test for categorical variables, as appropriate. Effect sizes for categorical comparisons were reported as Cramer's V, with values of 0.10, 0.30, and 0.50 considered small, medium, and large, respectively. p < 0.05 (two-sided) was considered statistically significant. Patients were consecutively enrolled at the time of rimegepant initiation in routine clinical practice, corresponding to a consecutive sampling approach.

Longitudinal changes in MHD and MMD were analyzed using generalized estimating equations (GEE), with repeated measurements nested within patients and assuming an exchangeable correlation structure and a normal distribution (R package “geepack”). This approach allowed inclusion of all available observations over time without requiring balanced follow-up across visits.²¹

Univariable analyses were first conducted to explore associations between baseline clinical variables and changes in MHD and MMD at 3 and 6 months. Variables with p < 0.10 in univariable analyses, together with clinically relevant covariable based on prior literature and biological plausibility, were considered for inclusion in multivariable models.

Multivariable models were constructed to identify independent predictors of outcome. Variables included in the models were selected based on clinical relevance and their association with the outcome in univariable analyses. All selected variables were entered simultaneously into the multivariable models to obtain adjusted effect estimates. The modelling approach also considered sample size constraints due to missing data. In this context, psychometric variables (HADS-A, HADS-D, and HIT-6) were not included in the primary multivariable models due to incomplete data availability and the potential reduction in statistical power. Full model outputs, including all variables entered in each model regardless of statistical significance, are reported in the Supplementary material (Table S1).

Analyses were performed using observed data at each time point. Response rates were calculated among evaluable patients at each visit. Patients who discontinued treatment due to lack of effectiveness or adverse events were classified as non-responders at the visit corresponding to the time of discontinuation. Specifically, individuals who discontinued at the 3-month assessment were included as non-responders in the 3-month response analysis, and those who discontinued between months 3 and 6 were included as non-responders in the 6-month response analysis. Patients without available outcome data at a given visit and without documented treatment discontinuation were not included in response calculations for that time point. No imputation of missing data was performed, and the study was not designed as a strict intention-to-treat analysis.

All statistical analyses were conducted using R software, version 4.4.0 (R Foundation for Statistical Computing, Vienna, Austria).

Ethical considerations

The study protocol was approved by the Drug Research Ethics Committee of Hospital Universitario de la Princesa (Comité de Ética de la Investigación con medicamentos, CEIm; registration number 5600, 6 June 2024). All participants provided their written informed consent electronically prior to enrolment. The study was conducted in accordance with the principles of the Declaration of Helsinki and complied with applicable data protection regulations.

Results

Study population

In total, 150 patients were included at baseline, and all of them completed at least 3 months of follow-up. At the time of analysis, 64 patients had reached and completed the 6-month visit. A total of 15 patients discontinued treatment follow-up due to lack of effectiveness and/or adverse events, including 10 at the 3-month visit and five between months 3 and 6. Further details are provided in Figure 1.

Figure 1.

Flowchart of patient follow-up throughout the study period.

The cohort comprised 150 patients, of whom 85.3% were female. Median age was 48 years, and 70.7% had episodic migraine. Patients had failed a median of 6 preventive treatments, with 54.7% having previously failed BoNT-A and 39.3% prior anti-CGRP mAbs. Medication overuse was present in 40% at baseline. Detailed baseline characteristics are presented in Table 1.

Table 1.

Baseline demographic and clinical characteristics of the study cohort (N = 150).

Variable	Total N = 150
Women (%)	128 (85.3%)
Age, median (IQR), years	48 (39–57)
Age at headache onset (years), median (IQR)	15 (12–22)
Diagnosis of episodic migraine, N (%)	106 (70.7%)
Failed preventive onabotulinumtoxinA (BoNT-A), N (%)	82 (54.7%)
Patients with concomitant treatment, N (%)	85 (56.7%)
Number of concomitant preventive treatments, median (IQR)	1 (0–1)
Concomitant onabotulinumtoxinA (BoNT-A), N (%)	15 (10%)
Subgroup 0–7 baseline MHD, N (%)	7 (4.7%)
Subgroup 8–14 baseline MHD, N (%)	99 (66%)
Subgroup >15 baseline MHD, N (%)	44 (29.3%)
Subgroup 0–7 baseline MMD, N (%)	30 (20%)
Subgroup 8–14 baseline MMD, N (%)	96 (64%)
Subgroup > 15 baseline MMD, N (%)	21 (14%)
Phenotypic characteristics (n (%)) (baseline)
Intensity (scale 0–10), median (IQR)	8 (7–9)
Presence of aura, N (%)	55 (36.7%)
Visual aura, N (%)	48 (32%)
Sensory aura, N (%)	12 (8%)
Aphasic aura, N (%)	6 (4%)
Prior treatment with anti-CGRP mAbs (n (%))
Patients previously treated with anti-CGRP mAbs, N (%)	59 (39.3%)
Erenumab, N (%)	38 (25.3%)
Fremanezumab, N (%)	15 (10%)
Galcanezumab, N (%)	42 (28%)
Eptinezumab, N (%)	4 (2.7%)

Data are expressed as number and percentage (n (%)) for categorical variables and median (interquartile range (IQR)) for continuous variables. MHD: monthly headache days; MMD: monthly migraine days; MO: medication overuse; BoNT-A: onabotulinumtoxinA; anti-CGRP mAbs: monoclonal antibodies targeting the calcitonin gene-related peptide pathway.

Real-world effectiveness of rimegepant: headache and migraine day reduction and clinical response

Rimegepant was associated with a significant reduction in monthly headache and migraine days at 3 months compared with baseline in the primary analytical cohort (n = 150). The analysis showed a mean decrease of −3.51 MHD from baseline to 3 months (95% CI = −1.68 to −5.35), with a statistically significant difference between time points (p < 0.001). Median MHD decreased from 12 (IQR = 10–15) at baseline to 7.5 (IQR = 5–15) at 3 months, also showing a significant change from baseline (p < 0.001) (Figure 2). Overall, headache frequency was reduced by 37.5% at 3 months.

Figure 2.

Changes in monthly headache days (A) and monthly migraine days (B) from baseline to 3 months of rimegepant treatment (n = 150). Box plots represent the median and interquartile range; individual data points are shown as dots, and black lines indicate the overall trend. Statistical comparisons were performed using generalized estimating equations. p < 0.05 was considered statistically significant.

MMD also significantly decreased within the first 3 months (Figure 2B), with a mean change of −2.89 days from baseline to 3 months (95% CI = −1.44 to −4.34), with a statistically significant difference between time points (p < 0.001), corresponding to a 43% reduction vs baseline. Median MMD was reduced by 40%, corresponding to a decrease from 10 (IQR = 8–12) to 6 (IQR = 3–10), also showing a significant change from baseline (p < 0.001).

To further characterize the effectiveness of rimegepant treatment, patients were stratified according to their degree of response: mild (≥ 30% to < 50%), good (≥ 50% to < 75%), excellent (≥ 75%), and full remission (100%). At 3 months, 36% of patients achieved a ≥ 50% reduction in MHD and 43% in MMD. Excellent responses (≥ 75%) were observed in 15% and 20% of patients, respectively, and 16 patients (11%) achieved full remission in MMD (Table 2).

Table 2.

Distribution of treatment response categories to rimegepant at 3 months (n = 150).

* outcome	≥ 30% (Mild+)	≥ 50% (Good+)	≥ 75% (Excellent+)	100% (Full remission)
MHD	51% (n = 77)	36% (n = 54)	15% (n = 22)	0% (n = 0)
MMD	51% (n = 77)	43% (n = 65)	20% (n = 30)	11% (n = 16)

* Response was defined as the percentage reduction from baseline in monthly headache days (MHD) or monthly migraine days (MMD), categorized as mild (≥ 30% to < 50%), good (≥ 50% to < 75%), excellent (≥ 75%), and full remission (100%). Values are expressed as percentages of the patients evaluated at this time point, with absolute numbers shown in parentheses.

These individual response patterns were further reflected in the low rate of treatment discontinuation due to lack of effectiveness. the first 3 months, 10 patients (7%) discontinued rimegepant due to insufficient benefit, including three patients (2%) in whom adverse events contributed to treatment discontinuation.

Changes in headache impact, anxiety/depression, and insomnia at 3 months

A subgroup of patients (n = 100) had HIT-6 data available at baseline and at 3 months. A significant improvement in quality of life was observed, with median HIT-6 scores decreasing from 64.5 (IQR = 61–68) at baseline to 59.5 (IQR = 45–78) at 3 months (p < 0.0001).

In addition, a subset of patients had available data for comorbid symptoms (n = 40 for HADS anxiety and depression scores, and n = 29 for ISI insomnia scores). When considering the subgroup as a whole, no statistically significant overall reductions in anxiety, depression, or insomnia scores were observed after 3 months of treatment. Nevertheless, a downward trend was noted in the median HADS-A and HADS-D scores, suggesting a possible improvement that may not have reached statistical significance due to the limited sample size (see Supplementary material, Figure S1). Given the small sample size, these analyses should be considered exploratory.

To further examine whether changes in these psychometric measures were associated with clinical effectiveness, patients were stratified according to treatment response and categorized as responders (≥ 50% reduction in monthly headache days or monthly migraine days) or non-responders (< 50%), as defined in the Methods.

Reductions in HADS-A (anxiety) scores were significantly greater among responders compared with non-responders, irrespective of whether response was defined according to MHD or MMD. For HADS-D (depression), significantly greater score reductions were observed only when response was defined by monthly headache day reduction, whereas differences were not statistically significant when response was based on monthly migraine day reduction. In contrast, changes in ISI (insomnia) scores did not differ significantly between responders and non-responders (Table 3).

Table 3.

Changes in psychometric scores according to treatment response at 3 months.

	* Response rates according to MHD reduction at 3 months			* Response rates according to MMD reduction at 3 months
	Non-responders (< 50%)	Responders (≥ 50%)	p-value	Non-responders (< 50%)	Responders (≥ 50%)	p-value
HADS-A (IQR)	1 (−1.25, 3)	−2 (−4.25, 0)	0.0014	1 (−2, 3)	−1.5 (−4.25, 3)	0.0241
HADS-D (IQR)	0 (−2, 2.5)	−2 (−4.25, −0.75)	0.0197	0 (−2.25, 5)	−1 (−3.25, 3)	0.2502
ISI (IQR)	0 (−1, 5)	0 (−2.75, 0)	0.1820	0 (−2.5, 3.75)	−1 (−1.5, 1)	0.7934

* Patients were categorized as responders (≥ 50% reduction in monthly headache days (MHD) or monthly migraine days (MMD)) or non-responders (< 50%). Values represent median change from baseline with interquartile range (IQR). Between-group comparisons were performed using the Mann–Whitney U test. p < 0.05 were considered statistically significant. HADS-A: Hospital Anxiety and Depression Scale – Anxiety subscale; HADS-D: Hospital Anxiety and Depression Scale – Depression subscale; ISI: Insomnia Severity Index.

Predictors of response to rimegepant in real-world clinical practice

Several clinical and treatment-related factors were significantly associated with treatment effectiveness in the univariable analyses (p < 0.05). All longitudinal analyses are presented as regression coefficients (β), representing adjusted differences in the number of MHD and MMD. Positive β values indicate a higher number of days, whereas negative values indicate a lower number of days associated with the variable of interest.

The variables that were significant in the univariable analysis for the longitudinal MHD outcome, considering both baseline and 3-month follow-up data, included the number of preventive treatments failed (β = 1.05, 95% CI = 1.02–1.07, p < 0.001), MO (β = 8.29, 95% CI = 5.89–10.68, p < 0.001), episodic migraine diagnosis (β = –11.42, 95% CI = −13.85 to −9.00, p < 0.001), prior use of anti-CGRP mAbs with (β = 7.98, 95% CI = 4.91–11.04, p < 0.001) or without (β = 6.82, 95% CI = 4.62–9.01, p < 0.001) prior botulinum toxin, prior botulinum toxin (β = –7.08, 95% CI = −12.42 to −1.74, p < 0.01) and scores on the HADS-A (β = 0.42, 95% CI = 0.22–0.62, p < 0.001), HADS-D (β = 0.45, 95% CI = 0.20–0.70, p < 0.001), and HIT-6 (β = 0.31, 95% CI = 0.22–0.40, p < 0.001) scales. Among these variables, those that remained significant in the multivariable analysis were MO (β = 5.22, 95% CI = 2.78–7.65, p = 0.001), prior failed use of anti-CGRP antibodies and botulinum toxin (β = 2.91, 95% CI = 0.55–5.27, p = 0.016) and episodic migraine diagnosis (β = –7.74, 95% CI = −10.64 to −4.85, p < 0.001). In contrast, the number of previously failed preventive treatments (β = −0.23, 95% CI = −0.38 to 0.78, p = 0.0509), prior use of anti-CGRP monoclonal antibodies (β = −0.54, 95% CI = −2.16 to 1.11, p = 0.52), and prior use of botulinum toxin (β = −0.62, 95% CI = −2.36 to 1.25, p = 0.53) were not significantly associated with the outcome (see Supplementary material, Table S1).

Likewise, in the univariable analysis of the longitudinal MMD outcome, significant variables included MO (β = 4.71 95% CI = 2.86–6.56, p < 0.001), episodic migraine diagnosis (β = –5.99, 95% CI = −8.32 to −3.66, p < 0.001), prior use of anti-CGRP mAbs with (β = 4.14, 95% CI = 1.98–6.31, p < 0.001) or without (β = 3.89, 95% CI = 2.13–5.65, p < 0.001) prior botulinum toxin, prior botulinum toxin (β = –2.69, 95% CI = −4.60 to −0.77, p = 0.006), as well as scores on the HADS-A (β = 0.29, 95% CI = 0.11–0.47, p = 0.002), HADS-D (β = 0.38, 95% CI = 0.14–0.62, p = 0.002), and HIT-6 (β = 0.29, 95% CI = 0.21–0.36, p < 0.001) scales, were also significant in the univariable analysis of the longitudinal MMD outcome. Of these, the variables that remained significant in the multivariable analysis were MO (β = 3.18, 95% CI = 1.28–5.08, p = 0.001) and episodic migraine diagnosis (β = –3.53, 95% CI = −6.20 to −0.87, p = 0.009). In contrast, prior use of both anti-CGRP antibodies and botulinum toxin (β = −0.26, 95% CI = −2.72 to 2.18, p = 0.83), prior use of botulinum toxin (β = −1.96, 95% CI = −4.20 to −0.27, p = 0.08), and prior use of anti-CGRP antibodies (β = 1.79, 95% CI = −0.15 to 3.74, p = 0.07) were not significantly associated with the outcome (see Supplementary material, Table S1).

Exploratory 6-month outcomes

At the time of analysis, 64 patients had completed the 6-month follow-up, allowing for longitudinal evaluation. Baseline demographic and clinical characteristics did not differ significantly between the overall cohort and the subgroup of patients who completed the 6-month follow-up, supporting the representativeness of the 6-month sample and the absence of relevant selection bias (see Supplementary material, Table S2).

Using all available observations, the GEE model demonstrated a significant reduction from baseline to 6 months in both MHD and MMD. When compared with baseline, the mean change in MHD at 6 months was −5.57 days (95% CI = −7.94 to −3.20, p < 0.001), while MMD decreased by −5.05 days (95% CI = −6.92 to −3.17, p < 0.001). This was reflected by a decrease in median MHD to 6 days (IQR = 5–15), and median MMD to 5 days (IQR = 1–8). The additional change from 3 to 6 months was −2.06 days for MHD (95% CI = −0.31 to −4.43, p = 0.083) and −2.16 days for MMD (95% CI = −0.29 to −4.02, p = 0.017) (Figure 3A and B).

Figure 3.

(A) monthly headache days (MHD) and (B) monthly migraine days (MMD) show the model-based analysis using the generalized estimating equations (GEE) model, including all available observations (n = 150). Across both analyses, a significant and progressive reduction in MHD and MMD was observed from baseline to 3 and 6 months. (C) MHD and (D) MMD display the complete-case analysis restricted to patients with available data at 6 months (n = 64). Box plots represent the median and interquartile range, dots correspond to individual patient data, and black lines indicate the overall temporal trend. Statistical comparisons in (A) and (B) were performed using GEE models. p < 0.05 was considered statistically significant.GEE: generalized estimating equations.

In parallel, a complete-case analysis was conducted. Only patients with available clinical data at the 6-month visit were included in the corresponding analysis (n = 64). Among these complete cases, compared to baseline, median MHD decreased by −5.05 days (95% CI = −7.49 to −2.61, p = 0.0001) at 3 months, with a further reduction at 6 months of −5.23 days (95% CI = −7.75 to −2.72, p < 0.0001). The additional change from 3 to 6 months was not significant (Figure 3C). For MMD, the median dropped −4.43 days at 3 months compared to baseline (95% CI = −6.23 to −2.63, p < 0.0001) and a further reduction of −4.55 days (95% CI = −6.37 to −2.73, p < 0.0001) was observed at 6 months (Figure 3D). Similar to MHD, the change from 3 to 6 months was not significant.

Following the same analytical approach used at 3 months, treatment effectiveness at 6 months was further characterized by stratifying patients according to their degree of response, as previously explained. Patients who discontinued treatment between months 3 and 6 due to lack of effectiveness or adverse events (n = 5) were included in the 6-month response analyses as non-responders. At 6 months, 48% of patients achieved a ≥ 50% reduction in MHD and 58% in MMD. Excellent responses (≥ 75%) were observed in 19% and 31% of patients, respectively, and 10 patients (16%) achieved complete remission for MMD (Table 4).

Table 4.

Distribution of treatment response categories to rimegepant at 6 months (n = 64).

Outcome*	≥ 30% (Mild+)	≥ 50% (Good+)	≥ 75% (Excellent+)	100% (Full remission)
MHD	63% (n = 40)	48% (n = 31)	19% (n = 12)	2% (n = 1)
MMD	64% (n = 41)	58% (n = 37)	31% (n = 20)	16% (n = 10)

When extending the longitudinal model to include 6-month data, univariable analyses identified the same significant variables as in the baseline and 3-month model.

In the multivariable model, MHD reduction remained significantly associated with MO (β = 2.35, 95% CI = 1.29–3.43, p < 0.0001), prior failed use of anti-CGRP mAbs and botulinum toxin (β = 1.15, 95% CI = 0.18–2.06, p = 0.0156) and episodic migraine diagnosis (β = –3.07, 95% CI = −4.16 to −2.05, p < 0.0001). However, the number of previously failed preventive treatments (β = –0.18, 95% CI = −0.31 to 0.00, p = 0.07), prior use of anti-CGRP monoclonal antibodies (β = 0.84, 95% CI = −0.12 to 1.71, p = 0.07), and prior use of botulinum toxin (β = –0.31, 95% CI = −1.65 to 1.00, p = 0.65) were not significantly associated with the outcome (see Supplementary material, Table S1).

For MMD, MO (β = 3.51, 95% CI = 1.79 to 5.24, p = 0.0001) and episodic migraine diagnosis (β = –3.24, 95% CI = −5.70 to −0.77, p = 0.01) also remained significant. On the other hand, prior use of both anti-CGRP antibodies and botulinum toxin (β = −0.02, 95% CI = −2.36 to 2.32, p = 0.98), prior use of botulinum toxin (β = −1.76, 95% CI = −3.90 to −0.38, p = 0.11), and prior use of anti-CGRP antibodies (β = 1.78, 95% CI = −0.05 to 3.61, p = 0.06) were not significantly associated with the outcome (see Supplementary material, Table S1).

Overall, the pattern of predictors at 6 months was consistent with that observed at 3 months, with the same variables retaining significance across both time points.

Episodic vs. chronic migraine: clinical features, treatment outcomes, and conversion rates

Among the study population, 106 patients had episodic migraine and 44 had chronic migraine at baseline and at the 3-month timepoint; at 6 months, the corresponding numbers were 47 and 17, respectively. Both groups were demographically comparable, with similar sex distribution, age at migraine onset, and age at study inclusion. Treatment burden was greater in the chronic group, which showed more prior preventive treatment failures (median 8 vs. 5, p < 0.001), a higher proportion of prior exposure to anti-CGRP monoclonal antibodies (80% vs. 32%, p < 0.001), and a higher frequency of medication overuse (78% vs. 22%, p < 0.001).

Regarding treatment effectiveness, reductions in MHD and MMD at 3 months were comparable between the two populations. However, differences became apparent by 6 months. Patients with chronic migraine experienced significantly greater absolute reductions in both headache and migraine days compared with those with episodic migraine (median MHD reduction −10 vs. −5 days, p = 0.007; median MMD reduction −8 vs. −4 days, p = 0.041). These results were consistent with the observed absolute values of MHD and MMD in both subpopulations (see Supplementary material, Figure S2). Nonetheless, these findings should be interpreted with caution, given the higher baseline headache frequency in chronic migraine. In addition, the smaller sample size at 6 months may limit the robustness of between-group comparisons (n = 17 in chronic migraine and n = 47 in episodic migraine).

Additional analyses examined treatment response categories as defined earlier. For MHD, the distribution of response categories did not differ significantly between chronic and episodic migraine at 3 months (χ² = 5.58, p = 0.13; Cramer's V = 0.13) or at 6 months (χ² = 2.78, p = 0.43; Cramer's V = 0.00). Within the chronic subgroup, the proportion of mild responders increased from 17% to 33%, while non-responders decreased from 33% to 25%. Similarly, for MMD, response distributions did not differ significantly between groups at 3 months (χ² = 5.78, p = 0.12; Cramer's V = 0.14) or at 6 months (χ² = 2.26, p = 0.52; Cramer's V = 0.00). In the chronic subgroup, non-responders decreased from 35% to 26%, and good responders (≥ 50% to < 75% response) increased from 20% to 24%.

Overall, these findings indicate comparable effectiveness of rimegepant in patients with episodic and chronic migraine, with greater absolute reductions at 6 months in the chronic subgroup, likely reflecting the higher baseline headache frequency in this population.

At 3 and 6 months, a progressive shift from chronic to episodic migraine was observed. In the overall cohort, the proportion of episodic migraine increased from 70.7% at baseline to 74% at 3 months and 81.3% at 6 months, with a corresponding decrease in chronic migraine. A similar pattern was observed in the complete-case analysis, supporting the consistency of this finding over time (see Supplementary material, Figure S3).In the most refractory population, defined as patients with prior failure to monoclonal antibodies, the proportion of episodic migraine increased from 49.3% at baseline to 55.1% at 3 months and 70.4% at 6 months, with a corresponding decrease in chronic migraine. A similar pattern was observed in the complete-case analysis, supporting the consistency of this finding over time (see Supplementary material, Figure S3).

Patients with prior anti-CGRP therapy: clinical features and treatment outcomes

Patients were stratified according to prior exposure to anti-CGRP monoclonal antibodies (mAbs) (Figure 4). For MHD, at 3 months, patients with prior mAb exposure showed a higher proportion of excellent responders compared with mAb-naïve patients (59% vs. 40%). At 6 months, this pattern was not maintained, with the prior-exposure group showing a higher rate of non-response (22% vs. 16%) (Figure 4B); however, the limited sample size at this time point (n = 27 vs. n = 37) warrants cautious interpretation.

Figure 4.

Response to rimegepant according to prior anti-CGRP therapy. Stacked bar plots represent the percentage of patients categorized as non-responders (< 30%), mild (≥ 30 to < 50%), good (≥ 50 to < 75%), and excellent responders (≥ 75%) based on the reduction at 3 months (n = 150) and 6 months (n = 64) in monthly headache days (A, B) and monthly migraine days (C,D). Percentages are calculated only among patients with available data; individuals with missing values are excluded from the denominators, and therefore total counts may not sum to the cohort n. Responses are stratified by prior exposure to anti-CGRP mAbs (“No” vs. “Yes”). Anti-CGRP mAbs: monoclonal antibodies targeting the calcitonin gene-related peptide pathway. MHD: monthly headache days; MMD: monthly migraine days.

For MMD, differences between groups were more pronounced at 3 months, with previously treated patients showing a higher proportion of non-responders (54% vs. 41%) and similar rates of excellent response. At 6 months, non-response rates were comparable between groups (37% vs. 36%) (Figure 4D), although the proportion of excellent responders remained lower among patients with prior mAb exposure (26% vs. 35%).

When patients were stratified according to the number of prior monoclonal antibody therapies (0–4), a clear gradient was observed in baseline disease severity and treatment refractoriness. The mean number of prior preventive therapies increased from 5 to 13 across strata (p < 0.001) (Table 5), accompanied by higher baseline headache burden.

Table 5.

Baseline demographic and clinical characteristics of subgroups stratified by the number of prior anti-CGRP therapies.

	Number of previously tested anti-CGRP mAbs
Characteristic	0	1	2	3	4	p-value²
Characteristic	N = 91¹	N = 25¹	N = 29¹	N = 4¹	N = 1¹	p-value²
Sex, N (%)						0.2
Women	81 (89%)	20 (80%)	23 (79%)	4 (100%)	0 (0%)
Age (years), median (IQR)	48 (37, 56)	52 (31, 58)	44 (39, 57)	66 (50, 81)	75 (75, 75)	0.3
Age at headache onset (years), median (IQR)	15 (12, 20)	14 (12, 20)	15 (10, 30)	28 (15, 40)	30 (30, 30)	0.6
Aura, N (%)	26 (29%)	12 (48%)	15 (52%)	2 (50%)	0 (0%)	0.082
Number of failed preventive treatments, median (IQR)	5 (3, 6)	8 (6, 10)	8 (7, 11)	14.5 (12, 15.5)	13 (13, 13)	< 0.001
Failed preventive onabotulinumtoxinA (BoNT-A), N (%)	34 (37%)	18 (72%)	25 (86%)	4 (100%)	1 (100%)	< 0.001
Patients with concomitant treatment, N (%)	53 (58%)	14 (56%)	14 (48%)	4 (100%)	0 (0%)	0.3
MHD baseline, median (IQR)	10 (9, 13)	12 (10, 14)	30 (15, 30)	15 (13, 23)	30 (30, 30)	< 0.001
MHD 3 months, median (IQR)	6 (4, 10)	10 (5, 15)	20 (11, 30)	18 (9, 26)	30 (30, 30)	< 0.001
MHD 6 months, median (IQR)	5 (3, 10)	6 (6, 8)	15 (8, 24)	19 (14, 23)	–	0.003
MMD baseline, median (IQR)	10 (8, 10)	9 (8, 12)	12 (8, 20)	13 (9, 22)	13 (13, 13)	0.017
MMD 3 months, median (IQR)	5 (2, 8)	6 (3, 10)	10 (5, 15)	15 (9, 19)	9 (9, 9)	0.011
MMD 6 months, median (IQR)	4 (1, 7)	5 (4, 7)	8 (5, 10)	18.5 (14, 23)	–	0.009
HIT-6 baseline, median (IQR)	64.5 (63, 69)	64.5 (61, 68)	65.5 (60.5, 66)	66 (64, 66)	64 (64, 64)	> 0.9
HIT-6 3 months, median (IQR)	59 (48, 65)	60 (54, 64)	53 (44, 64)	63 (45, 64)	63 (63, 63)	0.9
HIT-6 6 months, median (IQR)	54 (48, 64)	60 (50, 64)	61 (58, 63)	59 (53, 64)	–	0.9
MO baseline, N (%)	16 (18%)	13 (52%)	17 (59%)	2 (50%)	1 (100%)	< 0.001
MO 3 months, N (%)	10 (11%)	7 (28%)	14 (48%)	3 (75%)	1 (100%)	< 0.001
MO 6-Months, N (%)	3 (9%)	1 (11%)	6 (46%)	1 (50%)	–	0.010

n (%); Median (Q1, Q3).

Fisher's exact test; Kruskal–Wallis rank sum test; NA; Pearson's chi-squared test.

Data are reported as n (%) for categorical variables and as median (interquartile range (IQR)) for continuous variables. MHD: monthly headache days; MMD: monthly migraine days; BoNT-A: onabotulinumtoxinA; anti-CGRP mAbs: monoclonal antibodies targeting the calcitonin gene-related peptide pathway; HIT-6: Headache Impact Test-6; MO: medication overuse.

Clinically meaningful reductions in MHD and MMD were observed in patients with up to two prior antibody treatments. In contrast, patients with three or more prior therapies showed markedly reduced treatment response, with minimal changes over time; notably, those with four prior therapies did not exhibit improvement in MHD. Greater prior exposure to anti-CGRP mAbs was also associated with progressively higher baseline HIT-6 scores.

A substantial reduction in medication overuse was observed among patients with no or limited prior exposure, whereas no meaningful improvement was seen in those with extensive prior antibody use. Adverse event rates were comparable across subgroups.

To further explore the impact of prior therapeutic target, a subanalysis was conducted including only patients previously exposed to a single anti-CGRP target (receptor or ligand). Among the 59 patients with prior anti-CGRP therapy, 29 (19.3%) met this criterion, comprising eight patients treated with a receptor-targeting antibody and 21 with a ligand-targeting antibody. The remaining patients had not been previously treated with any anti-CGRP mAbs. Baseline demographic and clinical characteristics were broadly comparable between these groups (see Supplementary material, Table S3). Headache and migraine frequency at baseline, as well as changes in MHD and MMD at 3 and 6 months, did not differ meaningfully between groups. No additional clinically relevant differences in effectiveness or tolerability outcomes were detected.

Tolerability and adverse events

Rimegepant demonstrated a favorable tolerability profile throughout the study period. Most AEs were mild and of limited clinical relevance, with constipation (8%) and nausea (13%) being the most frequent at 3 months (Table 6). The overall incidence of AEs remained stable between 3 and 6 months. No new safety signals emerged over the follow-up period.

Table 6.

Frequency and type of adverse events (AE) reported at 3 and 6 months of treatment with rimegepant

Adverse events (n (%))	3 months (n = 150)	6 months (n = 64)
Constipation	12 (8%)	5 (8%)
Nausea	20 (13%)	5 (8%)
Dizziness	8 (5%)	6 (9%)
Fatigue	2 (1%)	0 (0%)
Urinary tract infection	2 (1%)	1 (2%)

Data are presented as the number of patients and percentage of the total sample. Percentages are based on the number of patients assessed at each time point.

According to the flowchart (Figure 1), three of the 150 patients discontinued treatment at 3 months due to adverse events, all in combination with insufficient therapeutic benefit, with nausea being the most frequently reported event leading to discontinuation. By month 6, two additional discontinuations were attributed to a combination of adverse events and insufficient benefit.

Discussion

This multicenter prospective real-world study shows that rimegepant is associated with clinically meaningful reductions in both MHD and MMD in a highly treatment-resistant population. At 3 months, median MHD decreased from 12 to 7.5 days and MMD from 10 to 6 days, reflecting a substantial reduction in headache burden. A considerable proportion of patients achieved clinically relevant responses, with ≥ 50% reduction observed in 36% of patients for MHD and 43% for MMD, and ≥ 75% reduction in 15% and 20%, respectively. Complete remission of MMD was achieved in 11% of patients at 3 months.

At 6 months, median MHD and MMD further decreased to 6 and 5 days, respectively. Responder rates remained favorable, with ≥ 50% reduction observed in 48% and 58% of patients, and ≥ 75% reduction in 19% and 31%, respectively, with complete remission in 16%. These analyses were limited to a subset of patients (n = 64) and should be considered exploratory, as changes between 3 and 6 months were not consistently statistically significant. In parallel, a progressive shift from chronic to episodic migraine was observed, with an approximate 10% reduction in chronic migraine, observed across analyses and extending to the most refractory patients. This finding is clinically relevant given the strong association between chronic migraine and disability.

When compared with randomized clinical trials, the magnitude of benefit observed in our study was broadly consistent. In the pivotal phase II/III trial,¹ rimegepant achieved an approximate reduction of 4.3 MMD weeks 9–12, with nearly half of patients attaining a ≥ 50% response. Although the absolute mean reduction in MMD at 3 months in our cohort (−2.89 days) was numerically smaller, the ≥ 50% responder rate (45%) was comparable despite greater baseline disease severity. Particularly relevant is the comparison with the phase IV trial by Pozo-Rosich et al.,⁸ conducted in patients with inadequate response to two to four traditional oral preventives but without prior exposure to CGRP-targeted therapies, in which rimegepant achieved a mean reduction of −2.1 MMDs. In our cohort, the observed reduction was numerically greater despite higher therapeutic complexity and prior treatment exposure. These findings extend previous observations from long-term studies² to a real-world population with substantial prior treatment exposure, although comparisons should be interpreted cautiously given differences in study design and patient populations.

Multivariable analyses identified medication overuse, prior exposure to anti-CGRP monoclonal antibodies combined with BoNT-A, and chronic migraine as independent predictors of poorer outcomes, whereas episodic migraine emerged as a consistent favorable predictor across endpoints and timepoints. These findings support a model in which baseline disease severity and cumulative treatment burden are key determinants of response and reinforce the potential benefit of earlier implementation of preventive strategies.²²

In line with this, treatment response declined progressively with increasing number of prior anti-CGRP therapies. This occurred in parallel with a progressively higher baseline disease burden across strata, including higher headache frequency, more preventive failures, and higher rates of medication overuse. Patients with up to two prior monoclonal antibodies achieved clinically meaningful reductions, whereas those with three or more showed attenuated responses, and no improvement was observed in patients with four prior therapies. A similar pattern was observed for medication overuse.

Taken together, these findings support a continuum of clinical refractoriness rather than target-specific resistance.²³ This pattern is consistent with observations from our atogepant cohort and the RESCUE study, in which the number of prior monoclonal antibodies, but not the therapeutic target, was associated with a lower probability of response.^24,25 Although some studies have suggested potential differences according to antibody type,²⁶ these findings have not been consistently replicated, and our subanalysis did not identify relevant differences between receptor- and ligand-targeting antibodies.

Despite the higher baseline disease burden in patients with prior anti-CGRP monoclonal antibody exposure, a relevant subset still achieved ≥ 50% and ≥ 75% reductions, indicating that prior mAb failure does not preclude clinical benefit with rimegepant. This may be explained by differences in mechanism of action between monoclonal antibodies and gepants, including receptor-level antagonism and differential blood–brain barrier penetration.

Beyond headache frequency, rimegepant was associated with clinically meaningful improvements in headache-related disability, reflected by a median −5 point reduction in HIT-6 scores at 3 months (p < 0.0001). Notably, prior trials did not systematically incorporate broader functional and affective outcomes^1,2 making these findings a complementary real-world contribution to the understanding of the wider clinical impact of preventive treatment. In the psychometric subgroup, improvements in anxiety and depressive symptoms were observed primarily among clinical responders, suggesting that these changes are driven by reductions in headache burden rather than a direct psychotropic effect. In contrast, insomnia scores remained stable and did not differ between responders and non-responders, consistent with previous real-world studies,^24,27 indicating that sleep disturbances may be less responsive to headache burden reduction or more difficult to capture in this context.

Rimegepant demonstrated a favorable and stable tolerability profile throughout follow-up. Adverse events were predominantly mild and gastrointestinal, with nausea (13%) and constipation (8%) most frequently reported, and no new safety signals observed at 6 months. These findings are consistent with pharmacovigilance data for gepants.^28,29 Discontinuation rates were low and driven mainly by insufficient effectiveness rather than tolerability, with 6.6% of patients discontinuing treatment at 3 months and very few cases attributed to adverse events. Overall, these findings support the good real-world tolerability of rimegepant even in a highly treatment-resistant population.

Several limitations should be acknowledged. Subgroup analyses included small sample sizes in some strata and should therefore be interpreted descriptively. Psychometric and sleep assessments were available only in a subset of patients, and 6-month outcomes should be considered exploratory due to incomplete follow-up at the time of analysis. Despite these limitations, the prospective design, use of standardized electronic case report forms, and inclusion of nine tertiary headache centers strengthen the reliability, clinical relevance, and external validity of our findings in routine practice.

Conclusions

In this prospective multicenter real-world study across nine tertiary headache centers, rimegepant was effective and well tolerated as a preventive treatment for migraine in a highly treatment-resistant population. Clinically meaningful reductions in monthly headache and migraine days were observed at 3 months, accompanied by a favorable tolerability profile characterized by predominantly mild adverse events and low discontinuation rates.

These findings support the use of rimegepant in routine clinical practice, including in patients with prior exposure to CGRP-targeted therapies, at the same time as highlighting the impact of cumulative disease burden and prior treatment exposure on treatment response. Greater benefit was observed in patients without medication overuse, with episodic migraine, and with limited prior exposure to anti-CGRP monoclonal antibodies or onabotulinumtoxinA. Overall, these results support a model of progressive clinical refractoriness and suggest that earlier use of rimegepant in the treatment course may be associated with greater clinical benefit.

Clinical implications

First prospective, multicenter real-world study of rimegepant (n = 150).

Effective at 3 months, even in highly treatment-resistant patients.

Clinically meaningful responses despite multiple prior failures.

Medication overuse, chronic migraine, and prior anti-CGRP mAbs/onabotulinumtoxinA were associated with poorer response.

Well tolerated, with improved headache impact and mood symptoms.

Supplemental Material

sj-docx-1-cep-10.1177_03331024261462836 - Supplemental material for Rimegepant for migraine prevention in clinical practice: A multicenter study including patients with prior anti-CGRP monoclonal antibody failure (GEMA project)

Supplemental material, sj-docx-1-cep-10.1177_03331024261462836 for Rimegepant for migraine prevention in clinical practice: A multicenter study including patients with prior anti-CGRP monoclonal antibody failure (GEMA project) by Ana Beatriz Gago-Veiga, Ana Belen Lopez-Rodriguez, Marina Sanchez Jimenez, Alvaro Iglesias Rubio, Nuria Montes, Javier Camiña Muñiz, Marta Dominguez Gallego, Carlos Calle De Miguel, Germán Latorre, Jaime Rodriguez-Vico, Alex Jaimes, Andrea Gomez Garcia, Sarai Urtiaga, Marta Gonzalez Salaices, Michele Dileone, Nuria Gonzalez-García, Jesús Porta-Etessam, María-Luz Cuadrado, Sonia Santos Lasaosa, Javier Díaz-De-Terán, Leonardo Portocarrero-Sánchez, Javier Casas-Limón and Iris Fernández-Lázaro in Cephalalgia

Supplemental Material

sj-png-2-cep-10.1177_03331024261462836 - Supplemental material for Rimegepant for migraine prevention in clinical practice: A multicenter study including patients with prior anti-CGRP monoclonal antibody failure (GEMA project)

Supplemental material, sj-png-2-cep-10.1177_03331024261462836 for Rimegepant for migraine prevention in clinical practice: A multicenter study including patients with prior anti-CGRP monoclonal antibody failure (GEMA project) by Ana Beatriz Gago-Veiga, Ana Belen Lopez-Rodriguez, Marina Sanchez Jimenez, Alvaro Iglesias Rubio, Nuria Montes, Javier Camiña Muñiz, Marta Dominguez Gallego, Carlos Calle De Miguel, Germán Latorre, Jaime Rodriguez-Vico, Alex Jaimes, Andrea Gomez Garcia, Sarai Urtiaga, Marta Gonzalez Salaices, Michele Dileone, Nuria Gonzalez-García, Jesús Porta-Etessam, María-Luz Cuadrado, Sonia Santos Lasaosa, Javier Díaz-De-Terán, Leonardo Portocarrero-Sánchez, Javier Casas-Limón and Iris Fernández-Lázaro in Cephalalgia

Supplemental Material

sj-png-3-cep-10.1177_03331024261462836 - Supplemental material for Rimegepant for migraine prevention in clinical practice: A multicenter study including patients with prior anti-CGRP monoclonal antibody failure (GEMA project)

Supplemental material, sj-png-3-cep-10.1177_03331024261462836 for Rimegepant for migraine prevention in clinical practice: A multicenter study including patients with prior anti-CGRP monoclonal antibody failure (GEMA project) by Ana Beatriz Gago-Veiga, Ana Belen Lopez-Rodriguez, Marina Sanchez Jimenez, Alvaro Iglesias Rubio, Nuria Montes, Javier Camiña Muñiz, Marta Dominguez Gallego, Carlos Calle De Miguel, Germán Latorre, Jaime Rodriguez-Vico, Alex Jaimes, Andrea Gomez Garcia, Sarai Urtiaga, Marta Gonzalez Salaices, Michele Dileone, Nuria Gonzalez-García, Jesús Porta-Etessam, María-Luz Cuadrado, Sonia Santos Lasaosa, Javier Díaz-De-Terán, Leonardo Portocarrero-Sánchez, Javier Casas-Limón and Iris Fernández-Lázaro in Cephalalgia

Supplemental Material

sj-png-4-cep-10.1177_03331024261462836 - Supplemental material for Rimegepant for migraine prevention in clinical practice: A multicenter study including patients with prior anti-CGRP monoclonal antibody failure (GEMA project)

Supplemental material, sj-png-4-cep-10.1177_03331024261462836 for Rimegepant for migraine prevention in clinical practice: A multicenter study including patients with prior anti-CGRP monoclonal antibody failure (GEMA project) by Ana Beatriz Gago-Veiga, Ana Belen Lopez-Rodriguez, Marina Sanchez Jimenez, Alvaro Iglesias Rubio, Nuria Montes, Javier Camiña Muñiz, Marta Dominguez Gallego, Carlos Calle De Miguel, Germán Latorre, Jaime Rodriguez-Vico, Alex Jaimes, Andrea Gomez Garcia, Sarai Urtiaga, Marta Gonzalez Salaices, Michele Dileone, Nuria Gonzalez-García, Jesús Porta-Etessam, María-Luz Cuadrado, Sonia Santos Lasaosa, Javier Díaz-De-Terán, Leonardo Portocarrero-Sánchez, Javier Casas-Limón and Iris Fernández-Lázaro in Cephalalgia

Footnotes

Acknowledgments

We thank the patients and researchers for their dedication.

ORCID iDs

Ana Beatriz Gago-Veiga

Ana Belen Lopez-Rodriguez

Nuria Montes

Nuria Gonzalez-García

Jesús Porta-Etessam

María-Luz Cuadrado

Iris Fernández-Lázaro

Ethical considerations

The study was approved by the Drug Research Ethics Committee of Hospital Universitario de la Princesa (CEIm; registration number 5600, 6 June 2024). The study complied with the Declaration of Helsinki and applicable data protection regulations.

Consent to participate

All participants provided written informed consent.

Author contributions

ABGV and IFL designed the study. ABGV, ABLR, and IFL drafted the manuscript and figures; ABGV, ABLR, NM, and IFL carried out data analysis; ABGV, MSJ, AIR, JCM, MDG, CCDM, GL, JRV, AJ, AGG, SU, MGS, MD, NGG, MLC, JPE, JCL, JDDT, LPS, and SSL were responsible for acquisition of data. All the authors revised the manuscript and approved the final manuscript.

Funding

This work was supported by the Instituto de Salud Carlos III (ISCIII) and Fondo Europeo de Desarrollo Regional (FEDER), through IMPaCT project PMP22/00158, and co-funded by the European Union through the Recovery, Transformation and Resilience Plan – Next Generation EU to ABGV and IFL.

Declaration of conflicting interests

ABG-V has received speaker honoraria and/or served as a clinical advisor for Novartis, Lilly, Organon, TEVA, Exeltis, Chiesi, Abbvie, Pfizer, Dr. Reddy's, and Lundbeck. She is the coordinator and principal investigator of a research IMPaCT project, grant number PMP22/00158. JCM has received speaker honoraria and/or served as a clinical advisor for Novartis, Lilly, Organon, TEVA, Exeltis, Chiesi, Abbvie, Pfizer, and Lundbeck. CCDM has received speaker honoraria for TEVA, Allergam-Abbvie, and Lundbeck. GLT has received speaker honoraria and/or served as a clinical advisor for Novartis, Lilly, Organon, TEVA, Abbvie, Pfizer, and Lundbeck. JRV has received speaker honoraria and/or served as a clinical advisor for Novartis, Lilly, Organon, TEVA, Exeltis, Chiesi, Abbvie, Pfizer, Dr Reddy's, and Lundbeck. AJ has received speaker honoraria and/or served as a clinical advisor for Lilly, TEVA, Organon, Allergan-Abbvie, and Lundbeck. NG-G has received honoraria from Novartis, Lilly, TEVA, Organon, Allergan-Abbvie and Lundbeck. JPE has received honoraria from Novartis, Lilly, TEVA, Organon, Allergan-Abbvie, and Lundbeck. M-LC has received honoraria as a consultant or lecturer for Novartis, Abbvie, Lundbeck, and Teva. JDDT has received speaker honoraria and/or served as a clinical advisor for Novartis, Lilly, Organon, TEVA, Exeltis, Chiesi, Abbvie, Pfizer, Dr Reddy's, and Lundbeck. SSL has received speaker honoraria and/or served as a clinical advisor for Novartis, Lilly, TEVA, Abbvie, Pfizer, and Lundbeck. JCL has received speaker honoraria from Abbvie, Lilly, Lundbeck, Novartis, Organon, Pfizer, and Teva. The remaining authors declare that they have no conflicts of interest.

Data availability statement

The data supporting the findings of this study are available from the corresponding author upon reasonable request.

Supplemental material

Supplemental material for this article is available online.

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