Atogepant reduces triptan use: a pharmacoeconomic analysis in migraine prevention

Abstract

Background

Migraine is a leading cause of disability worldwide, impairing quality of life and productivity. Preventive therapies aim to reduce attack frequency, severity and the need for acute medications. Oral atogepant (60 mg), a calcitonin gene-related peptide (CGRP) receptor antagonist, has recently expanded migraine prevention options. This study evaluated changes in triptan use after atogepant initiation using real-world data.

Methods

This retrospective observational study used administrative healthcare databases from the Local Health Unit of Modena (Italy). Adults with chronic or high-frequency episodic migraine initiating atogepant between November 2023 and December 2024 were identified. Triptan use and related costs were assessed in the 6 months before and after treatment initiation (index date), measured as dispensed dosage units.

Results

Among 95 patients (86% female; mean age 53.5 years), 55 triptan users were included in the analysis. Triptan use decreased in 45 patients (82%), with ≥ 60% reduction in 27 (49%) and complete discontinuation in 10. Median consumption decreased from 76 to 24 dosage units, and mean consumption from 88.1 to 45.2. This reduction was statistically significant (Wilcoxon signed-rank test, p < 0.001). This reduction corresponded to a decrease of €2,591 in triptan-related pharmaceutical expenditure within the study cohort.

Conclusion

Atogepant preventive treatment may substantially reduce acute migraine medication use in real-world practice, with potential clinical and economic benefits.

Background

Migraine is a prevalent and disabling primary headache disorder, characterized by attacks of unilateral, pulsating pain of moderate to severe intensity lasting 4–72 h [1]. Its etiology involves genetic susceptibility and behavioral or environmental triggers, including stress, diet, hormonal changes and external stimuli [2]. Affecting approximately 14–15% of the population and more common in women [3, 4], migraine is the second leading cause of disability worldwide [5]. Management includes acute and preventive strategies [6]. Acute treatment aims to relieve symptoms, following a stepwise approach: paracetamol and nonsteroidal anti-inflammatory drugs (NSAIDs) for mild-to-moderate attacks, and triptans for more severe episodes [7]. Gepants and ditans are effective alternatives in patients who do not respond to or cannot tolerate triptans, particularly those with cardiovascular contraindications, as they lack vasoconstrictive effects [8, 9]. Preventive therapies are indicated in patients with frequent or poorly controlled migraine to reduce attack burden and the risk of medication overuse headache (MOH). Traditional options include beta-blockers, calcium channel blockers, antidepressants, antiepileptic drugs and onabotulinumtoxin A for selected chronic migraine cases [10]. More recently, therapies targeting the calcitonin gene-related peptide (CGRP) pathway, including monoclonal antibodies administered monthly or quarterly, have expanded prophylactic options [11]. Atogepant, an oral CGRP receptor antagonist taken once daily, represents a further advancement in this field [12]. Real-world evidence is important to capture the effectiveness and healthcare resource utilization associated with preventive therapies in routine clinical practice. In this context, the present study aimed to assess changes in triptan consumption among patients with chronic or high-frequency episodic migraine following initiation of atogepant using administrative data from the Local Health Unit (LHU) of Modena.

Methods

Data sources and study design

This single-center retrospective observational study used administrative healthcare databases from the LHU of Modena. The main characteristics and methodological roles of the data sources are summarized in Table 1. Data sources included the Direct Distribution pharmaceutical flow (Farmaci ad Erogazione Diretta, FED), the Territorial Pharmaceutical Assistance flow (Assistenza Farmaceutica Territoriale, AFT) and the EzGAAC^® platform. The FED database collects information on drugs dispensed through hospital pharmacies and direct distribution services, including drug codes, dispensing date, quantity (dosage units), facility and costs. It was used to identify atogepant dispensations, assess switches from anti-CGRP monoclonal antibodies to gepants and capture triptans dispensed via direct distribution. The AFT database includes reimbursed medications dispensed through community pharmacies, with information on dispensing date, drug codes and quantities. It was used to capture triptan prescriptions outside hospital settings.

Table 1.

Characteristics and roles of data sources used in the study

Data source	Setting	Role in the study
FED (Farmaci ad Erogazione Diretta)	Direct distribution system within the Local Health Unit (hospital pharmacies and affiliated distribution centers)	Primary administrative data source for drug utilization and cost analyses
AFT (Assistenza Farmaceutica Territoriale)	Community pharmacy setting reimbursed by the National Health Service (territorial outpatient care)	Complementary data source to ensure capture of community-based prescriptions
EzGAAC® platform	Internal digital platform of the Local Health Unit for managing direct drug distribution at patient level	Validation and integration tool to confirm FED data at the individual patient level (not an independent source of dispensing events)

Dispensations through direct distribution were further verified using the EzGAAC^® platform, which provides patient-level dispensing histories, including drug codes, dates, quantities, facilities and cost centers. It was used to confirm atogepant and triptan dispensing within the AVEN formulary. Information on migraine subtype (chronic versus high-frequency episodic migraine) was retrieved from the clinical records of the Headache Center of the University Hospital of Modena, where all patients were diagnosed and prescribed atogepant in accordance with national reimbursement criteria, which require specialist confirmation of the diagnosis prior to prescription. The study was approved by the Area Vasta Emilia Nord Ethics Committee of Modena (protocol number: 125/2020/OSS/AOUMO) and conducted in accordance with the Declaration of Helsinki.

Patient characteristics

Inclusion criteria were: (i) adult age (≥ 18 years); (ii) diagnosis of chronic migraine (≥ 15 headache days per month for > 3 months, with migraine features on ≥ 8 days per month) or high-frequency episodic migraine (8–14 headache days per month) according to ICHD-3 criteria [13]; (iii) initiation of atogepant between November 2023 and December 2024; and (iv) residence within the LHU of Modena. Exclusion criteria were: (i) non-residence in the LHU of Modena; and (ii) absence of any recorded triptan dispensation in the 6 months preceding the index date. The date of the first atogepant dispensation was defined as the index date.

Outcomes

Two analyses were performed. First, an aggregate analysis of triptan consumption and related pharmaceutical expenditure was conducted at the LHU level for 2024. Second, at the patient level, triptan use and costs were assessed during the 6 months before and after the index date.

Drug consumption was measured as dispensed dosage units (e.g., tablets, pre-filled pens), and drugs were identified using the Anatomical Therapeutic Chemical (ATC) classification system.

Statistical analysis

Continuous variables were summarized as mean and standard deviation (SD) and as median with interquartile range (IQR), as appropriate. Categorical variables were reported as counts and percentages. Changes in triptan consumption before and after atogepant initiation were assessed at the individual patient level using the Wilcoxon signed-rank test, due to the non-normal distribution of dispensed dosage units. The proportion of patients with reduced triptan consumption after treatment initiation was calculated with exact 95% confidence intervals (CIs) and compared against a null proportion of 50% using an exact binomial test. All tests were two-sided, and p values < 0.05 were considered statistically significant.

Results

Between November 2023 and December 2024, a total of 95 patients initiating atogepant therapy within the LHU of Modena were identified. Patients were clinically managed and prescribed atogepant at the Headache Center of the University Hospital of Modena. The majority of patients were female (N = 82; 86%), and the mean age was 53.5 years. When stratified by age groups, the largest proportion of patients was observed in the 51–60 years age class (N = 41; 43%), followed by the 61–70 years age group (N = 21; 22%) and the 41–50 years age group (N = 16; 17%). Detailed demographic characteristics of the study population are reported in Table 2.

Table 2.

Demographic characteristics of patients initiating atogepant during the inclusion period

Demographic characteristics (n = 95)
Sex (females; %)	82; 86%
Age (mean)	53.5 years
Age classes
18–30 years (n; %)	6 (6%)
31–40 years (n, %)	7 (7%)
41–50 years (n, %)	16 (17%)
51–60 years (n, %)	41 (43%)
61–70 years (n, %)	21 (22%)
71–80 years (n, %)	4 (4%)

Variation in triptan consumption

Among the 95 identified patients, 26 (27%) were non-residents of the LHU of Modena and were excluded, as triptan prescriptions could not be tracked. An additional 14 patients (15%) were residents but had no recorded triptan dispensations, likely using medications not captured in the available databases. Among the 55 patients included in the analysis, 45 (82%) showed a reduction in triptan consumption after atogepant initiation, while 6 (11%) showed an increase and 4 (7%) no change. A total of 27 patients (49%) achieved a reduction of at least 60%, and 10 patients reached complete discontinuation (100% reduction). At the population level, triptan consumption significantly decreased after treatment initiation (Fig. 1). Median consumption declined from 76 dosage units in the 6 months before the index date to 24 dosage units in the 6 months after atogepant initiation. Mean consumption decreased from 88.1 to 45.2 dosage units. This reduction was statistically significant (Wilcoxon signed-rank test, p < 0.001). The proportion of patients showing a reduction in triptan use was 82% (exact 95% confidence interval approximately 69–91%), which was significantly greater than 50% (exact binomial test, p < 0.001).

Fig. 1.

Triptan consumption before and after atogepant initiation. Each thin line represents an individual patient. Values correspond to cumulative triptan consumption (dosage units) over the 6 months before and after atogepant initiation. Thick solid and dashed lines indicate the mean and median consumption, respectively

Changes in triptan consumption and related costs

At the LHU level, total pharmaceutical expenditure for triptans in Modena during 2024 was approximately €943,000. Given the limited number of patients initiating atogepant therapy, their impact on overall LHU expenditure was minimal. At the cohort level, a substantial reduction in triptan consumption and related costs was observed after atogepant initiation (Table 3; Fig. 2). Specifically, triptan pre-filled pens showed a reduction of approximately 71% in consumption and 68% in associated costs, while tablet formulations showed a reduction of approximately 49% in consumption and 51% in costs. Overall, total triptan consumption decreased by 60%, corresponding to a reduction of €2,591 in triptan-related pharmaceutical expenditure within the study cohort.

Table 3.

Changes in triptan consumption and related costs in the 6 months before and after the index date

Triptans formulations	6 months before index date		6 months after index date		Δ consumption	Δ costs
	Consumption	Costs	Consumption	Costs
Tablets	4861	2111€	2498	1031€	-2363 (-49%)	-1080€ (-51%)
Pre-filled pens	248	2227€	72	716€	-176 (-71%)	-1511€ (-68%)
Total	5109	4338€	2570	1747€	-2539 (-60%)	-2591€ (-59%)

Δ: absolute and percentage change between the 6 months before and the 6 months after the index date

Fig. 2.

Triptan costs before and after atogepant initiation in 55 patients with episodic and chronic migraine

Discussion

In this retrospective study based on administrative healthcare data, initiation of atogepant was associated with a statistically significant reduction in triptan consumption at the individual patient level. Approximately 82% of patients showed a decrease in triptan use, with nearly half achieving a reduction of at least 60% and a subset reaching complete discontinuation. These findings suggest that atogepant may effectively reduce the need for acute migraine medications in routine clinical practice. In the absence of a control group, the observed reduction cannot be attributed solely to atogepant: regression to the mean, the natural fluctuation of migraine over time and concurrent lifestyle or therapeutic changes may all contribute to the effect. Although causal inference cannot be established, the magnitude and consistency of the reduction are suggestive of a clinically meaningful effect. From a clinical perspective, the reduction in acute medication use represents a pragmatic indicator of preventive treatment effectiveness. Traditional endpoints such as monthly migraine days or disability scores are not always available in administrative datasets, whereas changes in rescue medication use can provide an easily measurable proxy of disease control. In this context, the observed reduction in triptan consumption may reflect a decrease in attack frequency and/or severity, translating into a lower need for symptomatic treatment. This type of endpoint may capture real-world treatment impact more directly than conventional efficacy measures, particularly in large, unselected populations. Our findings are consistent with emerging real-world evidence supporting the effectiveness of atogepant. Previous studies, including the GIANT study and the START registry, have demonstrated improvements in migraine-related outcomes, including reductions in pain intensity, disability and high patient satisfaction, even in populations with prior preventive treatment failures [14–16]. Our dataset does not include patient-reported outcomes, and we therefore cannot directly link the observed reduction in triptan use to changes in quality of life, disability, daily functioning or anxiety. Prior literature has shown that poor response to acute therapies is associated with greater disability and reduced quality of life [17], and that reduced reliance on acute medications has been associated with improvements in daily functioning [18]. Whether the same applies to the present cohort cannot be established from administrative data alone and remains a hypothesis to be tested in studies integrating clinical and patient-reported measures. Moreover, reduction in acute medication use may reflect a decrease in healthcare resource utilization and, potentially, in the overall economic burden associated with migraine. Indirect costs represent the largest component of migraine-related burden, accounting for approximately 60–80% of total costs in real-world studies, although estimates may vary depending on methodology and setting [19–21]. Reducing the use of acute migraine medications may also contribute to lowering the risk of MOH, a complication in patients with frequent migraine attacks and repeated use of symptomatic treatments [22, 23]. From an economic perspective, a corresponding reduction in pharmaceutical expenditure related to triptans was observed within the study cohort. Triptan-related costs decreased from €4,338 in the six months preceding atogepant initiation to €1,747 in the six months following treatment initiation, corresponding to an overall reduction of approximately €2,600. This reduction was consistent across formulations, with a more pronounced decrease observed for pre-filled pens compared with tablet formulations. This figure refers exclusively to the cost of triptans dispensed by the LHU and does not include the acquisition cost of atogepant, hospital or outpatient visits, diagnostics or indirect costs such as productivity loss. The present analysis therefore quantifies a single component of the overall pharmacoeconomic impact and should not be interpreted as a cost-utility evaluation. Although the limited number of atogepant users did not significantly impact the overall triptan expenditure of the LHU of Modena, estimated at approximately €943,000 in 2024, these findings provide a clear signal of potential cost savings at the individual level. When extrapolated to larger populations, such reductions may translate into meaningful economic benefits for healthcare systems. Given that the economic burden of migraine is largely driven by indirect costs [24, 25], reductions in acute medication use may also reflect improvements in functional capacity and productivity.

Limitations

This study has some limitations that should be considered when interpreting the findings. First, the single-arm, retrospective observational design without a parallel control group precludes any causal inference between atogepant initiation and the observed reduction in triptan use. The present findings are real-world signal that requires confirmation in larger and controlled studies. Second, the use of triptan consumption as a proxy for treatment effectiveness is pragmatic and well-suited to administrative datasets, but does not capture clinical outcomes such as migraine frequency, disability or patient-reported measures. Nevertheless, changes in acute medication use represent a meaningful and widely adopted indirect indicator of disease control, particularly in large, unselected populations where clinical data may not be systematically available [26, 27]. Third, administrative databases capture drug dispensations rather than actual medication intake. As a consequence, our estimates do not capture individual non-adherence, and stockpiling behaviour may have inflated pre-index consumption or smoothed post-index reductions. The direction of this bias is not predictable a priori, and our results should be interpreted accordingly. Nevertheless, dispensing-based exposure assessment is the standard approach in pharmacoepidemiology and provides a reliable measure at the population level. Fourth, the relatively small analytical cohort (n = 55), although adequate to detect the large effect observed at the population level, limits the precision of subgroup estimates and the ability to detect more subtle effects, including differential responses across age groups, sex or migraine subtype. Finally, the economic analysis was restricted to direct pharmaceutical costs related to triptans. Atogepant acquisition costs were not included, as the drug was made available within the LHU at a symbolic, non-negotiated price during the study period; this precluded any formal cost-effectiveness or cost–utility evaluation. Likewise, broader healthcare resource utilization and indirect costs were outside the scope of the available datasets. Despite these limitations, this study provides novel real-world evidence on the impact of atogepant on acute medication use and related costs, offering an original contribution to the literature on migraine prevention. Future studies integrating administrative data with clinical and patient-reported outcomes will help to further contextualize these findings.

Conclusions

In this real-world analysis, initiation of atogepant was associated with a substantial reduction in triptan use among patients with chronic or high-frequency episodic migraine. Effective preventive treatment for migraine may translate into reduced reliance on acute medications. Whether this reduction reflects improvements in disease burden, disability or patient functioning could not be assessed in the present study and remains to be confirmed by studies integrating clinical and patient-reported outcomes.

Author contributions

Simona Guerzoni and Francesca Gandolfi conceived and coordinated the study, contributed to the study design, and supervised data collection and interpretation. Lanfranco Pellesi performed the statistical analysis, contributed to data interpretation and drafted the manuscript. Flavia Lo Castro and Lisa Giannessi contributed to data interpretation and manuscript drafting and revision. Maria Chiara Olivieri contributed to data collection, data management, and preliminary analysis as part of her thesis work. All authors critically revised the manuscript for important intellectual content, approved the final version for publication and agree to be accountable for all aspects of the work.

Funding

The authors received no direct or indirect funds in relation to this manuscript.

Data availability

All data supporting the findings of this study are available within the paper.

Declarations

Ethics approval and consent to participate

The study was approved by the Area Vasta Emilia Nord Ethics Committee of Modena (protocol number: 125/2020/OSS/AOUMO) and conducted in accordance with the Declaration of Helsinki.

Consent for publication

Not applicable.

Competing interests

Simona Guerzoni has received speaker honoraria and consulting fees from Teva, Eli Lilly/Organon, Abbvie, Pfizer, Organon and Lundbeck. Lanfranco Pellesi has received consulting fees from Eli Lilly and serves as an editorial board member; no involvement occurred in any review or editorial decision-making process related to this paper. Flavia Lo Castro has received speaker honoraria from Organon and AbbVie. The other authors report no competing interests in relation to this manuscript.