A comparison of the persistence of acute treatment with rimegepant versus oral triptans in patients with migraine: A retrospective analysis of US claims data

Abstract

Background

This study compared persistence of patients initiating rimegepant versus oral triptans for the acute treatment of migraine.

Methods

A retrospective cohort analysis was conducted using US MarketScan claims data (1 March 2019 to 30 June 2023) among commercially- and US federal Medicare-insured migraine patients initiating rimegepant or oral triptans. Persistence was defined as having ≥1 refill within 12 months of initial prescription and was compared between propensity score-matched rimegepant and triptan cohorts.

Results

Before matching, 13,599 patients were identified in the rimegepant cohort and 38,127 in the triptan cohort. After matching, each cohort included 9909 patients. Significantly more rimegepant patients were persistent (75.8%) versus triptan patients (53.5%) (odds ratio [OR] 2.72, 95% confidence interval [CI] 2.56–2.90). Subgroup analyses showed similar trends for rimegepant versus specific triptans (rizatriptan: OR 2.49 [95% CI 2.33–2.67], and sumatriptan: OR 2.92 [95% CI 2.73–3.12]) and in patients with chronic migraine (OR 2.86 [95% CI 2.53–3.23]).

Conclusions

This study provides compelling evidence that rimegepant is associated with greater persistence than oral triptans for real-world acute treatment of migraine. Rimegepant is a favorable option for patients seeking effective and tolerable long-term treatment, particularly for those with insufficient response, intolerability, or contraindications to triptans.

Graphical abstract

This is a visual representation of the abstract.

Keywords

migraine acute treatment persistence rimegepant triptans real-world data

Introduction

While the acute treatment of migraine is informed by well-established conventions, typically recommending oral triptans taken as needed (pro re nata, PRN) as initial therapy (1,2), their implementation in the real-world setting may be impacted by numerous factors. At the time of PRN treatment, the burden of the decision to treat lies entirely with the patient. Patients are instructed to treat migraine attacks as early as possible for the most effective result and to prevent progression from episodic migraine to more disabling chronic migraine (“chronification”) (3,4), but are cautioned not to use medication too frequently due to the risk of medication-overuse headache (MOH) (5). Patients must combine these instructions with their own prior experiences to make an appropriate treatment decision. This decision to treat encompasses multiple contributing choices, starting with whether to let the migraine take its course without treatment (depending on severity, the patient's planned activities, etc.). If taking an acute treatment, patients must further decide a) which to use, and b) when to initiate treatment relative to attack onset.

Persistence, or the choice to continue with a therapy, can be viewed through the lens of behavioral economics, which explores human behavior and decision-making (6). In this way, persistence reflects a patient's decision on whether there is a net benefit in treatment continuation. Consequently, persistence can comprise an extensive range of patient-relevant treatment outcomes and will reflect patient satisfaction and the broader value of a given migraine therapy in the real-world setting, beyond what is possible to measure in clinical trials.

Factors that influence a patient's acute treatment decision, particularly with triptans, include: 1) probability and expected degree of treatment efficacy, including probability of headache recurrence after migraine resolution (based on patients’ past experiences); 2) risk of side effects with some treatments (e.g., dizziness, chest/neck discomfort, fatigue, brain fog) which may inhibit return to function even if some symptom relief is achieved; and 3) risk of MOH (i.e., patients are instructed to treat with triptans for a limited number of days per week/month to avoid chronification). All of these aspects influence patient satisfaction with a given treatment, which will be reflected in persistence of that treatment over the long term (7). For example, evidence suggests that at least 30% of new triptan users experience suboptimal response due to insufficient or inconsistent effectiveness and/or poor tolerability, and consequently either discontinue triptan use or continue to use concomitant non-triptan medications (8).

Oral calcitonin gene-related peptide (CGRP) receptor antagonists (gepants) are a novel class of medications with a different efficacy and tolerability profile than triptans (9). In particular, no identified evidence suggests an increased risk of MOH with frequent gepant use; rather, frequent use is associated with decreased monthly migraine days and prevalence of MOH overall (10,11). Across routes of administration, frequent CGRP receptor antagonist use has been associated with a decrease in number of headache days for patients with MOH (12 –14).

Oral rimegepant 75-mg is a gepant approved for the acute treatment of migraine with or without aura and for the preventive treatment of episodic migraine in adults. Clinical studies demonstrate that rimegepant provides rapid and durable benefits in the acute treatment of migraine with low rates of adverse events (15 –17), notably in patients with a history of triptan failure (18). Gepants are currently recommended by international consensus statements and practice recommendations for patients who do not show sufficient response to, or are contraindicated from oral triptans, even after attempting multiple doses and routes of administration (1,2,19,20). The 2024 International Headache Society practice recommendations suggest trying gepants after three triptans (2), although reducing this to just two triptans is increasingly being recommended, including by the American Headache Society (1,19,20). Moreover, real-world evidence suggests that switching from one triptan to another is neither associated with reductions in headache-related disability (21,22), nor with improvements in treatment continuation (23,24). However, large, comparative database studies of persistence on treatment with gepants and triptans in acute migraine treatment are lacking, as the triptan persistence evaluations included in these studies preceded the advent of gepants.

In light of these considerations, the primary objective of this study was to compare the proportion of persistent patients between cohorts receiving rimegepant and oral triptans for the acute treatment of migraine in a large US claims database. Oral triptan formulations including orally dissolving formulations (ODTs) were selected for comparability to rimegepant, which is available only as an ODT. Secondary objectives compared the persistence between cohorts receiving rimegepant and specific oral triptans (rizatriptan, sumatriptan), and in patients diagnosed with chronic migraine. This study used persistence, a reflection of patients’ individual risk-benefit assessment in treatment decision-making, as a key outcome measure to more comprehensively understand the real-world utility and comparative effectiveness of these treatments, beyond traditional pain-based efficacy endpoints.

Methods

Data source

This retrospective cohort study utilized commercially- and federal Medicare-insured patients with migraine using US claims data (MarketScan Commercial Claims and Encounters and Medicare Supplemental administrative databases), which contain linked longitudinal medical and pharmacy claims for privately insured individuals and their dependents, including large, self-insured, employer-provided, Medicare Advantage and Medicare Supplemental health insurance plans.

Analytic population

The study population consisted of adult patients (≥18 years) with a diagnosis of migraine (ICD-10-CM code: G43.xxx) who newly initiated rimegepant (quantity of eight tablets) or oral triptans (30 days’ supply). Rimegepant is indicated for both the prevention and acute treatment of migraine at the same dose, but with different dosing schedules (every other day and PRN, respectively). As this information was not available in the claims databases, a quantity of eight tablets was used as a proxy for acute treatment using PRN dosing with rimegepant. This threshold was selected to reduce inclusion of preventive indications (equivalent to ≥15 tablets). A similar approach of using the number of tablets to define acute treatment was employed previously to identify new users of rimegepant in claims data (25). Patients were excluded from the study cohort if, within 12 months prior to the index date, they had prescriptions for rimegepant, ubrogepant, atogepant, or lasmiditan. Only patients in the rimegepant cohort were allowed to have triptan experience (see Online Supplementary Figure 1 for study design).

Subgroup analyses were conducted in patients diagnosed with chronic migraine (ICD-10-CM code: G43.701, G43.709, G43.711, G43.719) during the baseline period or on the index date. This subgroup analysis aimed to limit confounding by selecting a population with greater overlap in baseline characteristics between the rimegepant and triptan cohorts.

Two more subgroup analyses were conducted to compare the persistence of treatment between rimegepant and specific oral triptans (rizatriptan, including both oral and ODT, and oral sumatriptan). The aim of these analyses was to help establish the generalizability of the primary analyses to clinical practice outside the US where the most commonly prescribed triptans may differ. These specific oral triptans were selected because they had sufficient sample size and overlap in patient characteristics with the rimegepant cohort for propensity score matching (PSM).

Study design

The study period spanned between 1 March 2019 to 30 June 2023 (Online Supplementary Figure 1). This included an identification period (1 March 2020 to 30 June 2023) during which patients had to have an index initial prescription for rimegepant (quantity of eight tablets) or oral triptan (30 days’ supply), as well as a minimum of 12 months’ continuous enrollment both before and after the index date. The earliest date in the identification period was selected to align with the FDA approval of rimegepant for acute treatment of migraine (27 February 2020), and to ensure that cohorts were contemporaneous. The baseline period comprised the twelve months prior to the index date. The follow-up period spanned 12 months, beginning one day post-index. Patients were required to have had a migraine diagnosis on or before the index date and be aged ≥18 years on the index date.

This study was conducted according to legal and regulatory requirements and followed generally accepted research practices, including Good Practices for Outcomes Research issued by the International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Institutional Review Board approval was not required, as only de-identified claims data were used.

Outcomes

The primary endpoint of this study was the persistence on newly prescribed rimegepant (prescribed quantity of eight tablets, as a proxy for acute use) versus oral triptans (30 days’ supply). Persistence was a binary outcome, defined as the occurrence of ≥1 refill (regardless of quantity of tablets or days’ supply) of the same molecule and same route of administration as the index treatment within 12 months post-index. As rimegepant and triptans were used PRN, measures of persistence based on the number of refills over a period of time are an appropriate metric (26). Twelve months was considered an adequate time period to allow for most patients with low migraine frequency to have a repeat claim. This definition was used to reduce the instance of low-frequency treatment being classified as non-persistent.

Statistical analysis

Descriptive statistics (mean, standard deviation, median, and inter-quartile range for continuous variables; counts and proportions for categorical variables) were used to summarize baseline patient characteristics. Comparative analyses employed PSM to adjust for confounding variables. The predicted probability of being in one cohort versus the other (rimegepant versus triptan) was estimated via multiple logistic regression, accounting for age, calendar year of index date, sex, menstrual migraine, insurance type, region, relevant comorbidities (depression, anxiety, seizures) within the six months prior to index, and preventive treatment use within the 12 months prior to index. Prior acute treatments were not included in the regression as there was insufficient overlap between cohorts; due to prior authorization requirements in the US, rimegepant is often used later in the treatment pathway than triptans, leading to substantial differences in prior treatment profiles of the two populations. PSM was conducted using 1:1 nearest neighbor matching (i.e., greedy matching) without replacement, with additional exact matching based on sex. Standardized mean differences (SMD) were calculated to compare various baseline characteristics between treatment cohorts, both before and after matching, with a threshold SMD < 0.1 used to indicate a good balance of these variables after PSM. De novo PSM was applied to subgroups. The percentage of patients classified as persistent in the matched cohorts was reported, along with odds ratios (ORs), 95% confidence intervals (CIs), and p-values. No additional methods were used to account for missing data.

Sensitivity analyses evaluated the impact of variable follow-up periods (six and 18 months) and refining the definition of persistence to include only patients with ≥2 refills of the same treatment within 12 months post-index. Reducing the follow-up period to six months and ≥2 refills were considered stricter definitions resulting in a population of more frequent treatment users, while increasing the follow-up period to 18 months was considered a less strict definition resulting in a population that included more infrequent treatment users. To assess the strength of a hypothetical unmeasured confounder that might explain away a specific treatment-outcome association, an analysis using the E-value method was conducted (27).

SAS statistical software (version 9.4, SAS Institute, Cary, North Carolina) was used for all calculations. P-values < 0.05 were considered statistically significant.

Results

The analysis utilized data from the MarketScan database between 1 March 2019 and 30 June 2023, which included a total of 46,297,440 enrollees (Online Supplementary Table 1). After applying the eligibility criteria, 13,599 patients were identified in the rimegepant cohort and 38,127 patients in the triptan cohort prior to matching. The most commonly prescribed triptans were sumatriptan (66.8%), rizatriptan (26.3%) and eletriptan (3.0%). Before matching, the cohorts differed in several baseline characteristics (i.e., SMD > 0.1). The rimegepant cohort compared to the triptan cohort were older (mean age 43.2 versus 39.5 years) and had a greater proportion of women (87.8% versus 82.0%) (Table 1). More patients in the rimegepant cohort had ≥1 triptan contraindication or ≥2 cardiovascular risk factors (49.7% versus 36.9%), and other comorbidities such as depression (23.9% versus 18.0%). Reflecting prior authorization requirements, patients in the rimegepant cohort had higher previous usage of acute treatments, including non-steroidal anti-inflammatory drugs (NSAIDs)(34.2% versus 24.8%) and opioids (30.1% versus 20.9%). In addition, 53.5% had prior triptan experience. Furthermore, a larger proportion had received ≥1 prior conventional oral preventive treatment (59.7% versus 29.0%) (Table 2).

Table 1.

Baseline demographics and clinical characteristics pre- and post-matching.

Characteristic, n (%)	Pre-matched cohorts			Post-matched cohorts
Characteristic, n (%)	Rimegepantn = 13,599	Oral triptann = 38,127	STDiff	Rimegepantn = 9909	Oral triptann = 9909	STDiff
Calendar year
2020	3905 (28.72)	14,343 (37.62)	0.19	2716 (27.41)	2567 (25.91)	0.03
2021	6502 (47.81)	16,225 (42.56)		4674 (47.17)	4745 (47.89)
2022	3192 (23.47)	7559 (19.83)		2519 (25.42)	2597 (26.21)
Age, mean (SD)	43.17 (11.54)	39.46 (12.38)	−0.31	42.63 (11.65)	42.93 (11.98)	0.03
Sex
Female	11,936 (87.77)	31,262 (81.99)	−0.16	8628 (87.07)	8628 (87.07)	0.00
Male	1663 (12.23)	6865 (18.01)	−0.16	1281 (12.93)	1281 (12.93)	0.00
Insurance
Commercial	13,453 (98.93)	37,729 (98.96)	0.00	9801 (98.91)	9795 (98.85)	−0.01
Medicare	146 (1.07)	398 (1.04)	0.00	108 (1.09)	114 (1.15)	−0.01
Region
Northeast	1631 (11.99)	4236 (11.11)	0.22	1168 (11.79)	1157 (11.68)	0.05
North Central	2876 (21.15)	8636 (22.65)		2041 (20.6)	1935 (19.53)
South	7519 (55.29)	18,050 (47.34)		5507 (55.58)	5739 (57.92)
West	1562 (11.49)	7164 (18.79)		1193 (12.04)	1078 (10.88)
Unknown	11 (0.08)	41 (0.11)		0 (0)	0(0)
Menstrual migraine	283 (2.08)	307 (0.81)	0.11	209 (2.11)	202 (2.04)	0.00
Triptan contraindications and warnings
Ischemic CVD	551 (4.05)	631 (1.65)	0.14	378 (3.81)	389 (3.93)	−0.01
Other cerebrovascular or CVD	298 (2.19)	265 (0.7)	0.13	186 (1.88)	197 (1.99)	−0.01
Uncontrolled hypertension	2842 (20.9)	5498 (14.42)	0.17	2020 (20.39)	2038 (20.57)	0.00
Ischemic heart disease	350 (2.57)	403 (1.06)	0.11	236 (2.38)	253 (2.55)	−0.01
Peripheral artery disease	221 (1.63)	306 (0.8)	0.08	149 (1.5)	153 (1.54)	0.00
Other significant CVD contraindications
Structural heart disease	442 (3.25)	650 (1.7)	0.10	295 (2.98)	312 (3.15)	−0.01
Arrhythmias	475 (3.49)	682 (1.79)	0.11	295 (2.98)	307 (3.1)	−0.01
Cardiac surgery	78 (0.57)	75 (0.2)	0.06	44 (0.44)	41 (0.41)	0.00
Other cardiac conditions	559 (4.11)	1014 (2.66)	0.08	385 (3.89)	377 (3.8)	0.00
Cardiovascular risk factors
Hypertension	3530 (25.96)	7065 (18.53)	0.18	2491 (25.14)	2480 (25.03)	0.00
Hyperlipidemia	3488 (25.65)	6243 (16.37)	0.23	2447 (24.69)	2396 (24.18)	0.01
Diabetes mellitus	1488 (10.94)	2968 (7.78)	0.11	1034 (10.43)	952 (9.61)	0.03
Obesity	2977 (21.89)	6326 (16.59)	0.13	2169 (21.89)	2158 (21.78)	0.00
Smoking	432 (3.18)	1182 (3.1)	0.00	310 (3.13)	278 (2.81)	0.02
Other comorbidities
Depression	3252 (23.91)	6858 (17.99)	0.15	2207 (22.27)	2220 (22.4)	0.00
Anxiety and related disorders	4323 (31.79)	9265 (24.3)	0.17	2985 (30.12)	3084 (31.12)	−0.02
Seizures	771 (5.67)	1173 (3.08)	0.13	522 (5.27)	510 (5.15)	0.01
Prevention agents
Beta blockers	2533 (18.63)	4192 (10.99)	0.22	1710 (17.26)	1725 (17.41)	0.00
Tricyclic antidepressants	1935 (14.23)	3409 (8.94)	0.17	1390 (14.03)	1385 (13.98)	0.00
Antidepressants	1990 (14.63)	3026 (7.94)	0.21	1250 (12.61)	1181 (11.92)	0.02
Anticonvulsants	3262 (23.99)	4988 (13.08)	0.28	2281 (23.02)	2319 (23.4)	−0.01
Anti-CGRP mAbs	3817 (28.07)	861 (2.26)	0.77	1056 (10.66)	860 (8.68)	0.07
Onabotulinumtoxin A	1861 (13.68)	452 (1.19)	0.49	541 (5.46)	452 (4.56)	0.04

CGRP: calcitonin gene-related peptide; CVD: cardiovascular disease; mAbs: monoclonal antibodies; SD: standard deviation.

Table 2.

Migraine acute and preventive treatments utilized during 12-month pre-index period.

Migraine therapies, n (%)	All (N = 51,726)	Rimegepant cohort (N = 13,599)	Oral triptan cohort (N = 38,127)
Acute Agents
Triptans	7388 (14.28)	7388 (53.33)	0 (0.00)
Oral triptans	7071 (13.67)	7071 (52)	0 (0.00)
Nasal triptans	387 (0.75)	387 (2.85)	0 (0.00)
Injectable triptans	377 (0.73)	377 (2.77)	0 (0.00)
Ergots	164 (0.32)	127 (0.93)	37 (0.1)
Nasal dihydroergotamine	105 (0.20)	85 (0.63)	20 (0.05)
Injectable dihydroergotamine	35 (0.07)	29 (0.21)	6 (0.02)
Butalbital	4329 (8.37)	1753 (12.89)	2576 (6.76)
NSAIDs	14,119 (27.30)	4651 (34.20)	9468 (24.83)
Nasal NSAIDs	27 (0.052)	25 (0.18)	2 (0.01)
Injectable NSAIDs	100 (0.19)	81 (0.6)	19 (0.05)
Acetaminophen	4255 (8.23)	1703 (12.52)	2552 (6.69)
Opioids and combinations	12,067 (23.33)	4094 (30.11)	7973 (20.91)
Isometheptene combinations	1 (0.00)	1 (0.01)	0 (0)
Antiemetics (migraine)	5237 (10.12)	2401 (17.66)	2836 (7.44)
Antiemetics (other)	11,031 (21.33)	4264 (31.36)	6767 (17.75)
Any acute injectable	494 (0.96)	470 (3.46)	24 (0.06)
Any acute intranasal	505 (0.98)	483 (3.55)	22 (0.06)
Any non-oral acute treatment*	2240 (4.33)	1332 (9.79)	908 (2.38)
Used at least 2 triptans during pre-index	1418 (2.74)	1418 (10.43)	0 (0)
Preventive agents
Beta blockers	6479 (12.53)	2842 (20.9)	3637 (9.54)
ACEi/ARBs	2724 (5.27)	850 (6.25)	1874 (4.92)
Tricyclic antidepressants	4623 (8.94)	2231 (16,41)	2392 (6.27)
Anti-depressants	5412 (10.46)	2260 (16,62)	3152 (8.27)
Anticonvulsants	7050 (13.63)	3736 (27.47)	3314 (8.69)
Anti-CGRP monoclonal antibodies	4754 (9.19)	3917 (28.8)	837 (2.2)
Onabotulinumtoxin A	2507 (4.85)	1991 (14.64)	516 (1.35)
Used ≥1 conventional oral prevention agent during pre-index	19,171 (37.06)	8112 (59.65)	11,059 (29.01)
Used ≥2 conventional oral prevention agent during pre-index	5736 (11.09)	3017 (22.19)	2719 (7.13)

*Includes parenteral or nasal sumatriptan and nasal zolmitriptan. ACEi: angiotensin-converting enzyme inhibitors; ARB: angiotensin II receptor blocker; CGRP: calcitonin gene-related peptide; mAb: monoclonal antibody; NSAID: non-steroidal anti-inflammatory drug.

After applying PSM, the primary analysis included 9909 patients in each cohort, and baseline characteristics were similar between cohorts (SMD < 0.1) (Table 1). The primary outcome analysis found that significantly more patients were classified as persistent in the rimegepant cohort (75.8%) compared to the triptan cohort (53.5%; OR: 2.72, 95%CI 2.56–2.90, p < 0.001) (Table 3, Online Supplementary Figure 2).

Table 3.

Proportion of patients persistent in rimegepant versus oral triptan cohorts (post-propensity score matching).

Outcome	Primary analysis		Subgroup 1: rimegepant vs oral rizatriptan		Subgroup 2: rimegepant vs oral sumatriptan		Subgroup 3: chronic migraine
Outcome	Rimegepant(n = 9909)	Oral triptan(n = 9909)	Rimegepant(n = 8747)	Oral triptan(n = 8747)	Rimegepant(n = 9046)	Oral triptan(n = 9046)	Rimegepant(n = 2935)	Oral triptan(n = 2935)
Proportion of patients persistent, n (%)	7510 (75.79)	5297 (53.46)	6568 (75.09)	4818 (55.08)	6834 (75.55)	4643 (51.33)	2290 (78.02)	1644 (56.01)
Odds ratio (95% CI)	2.72 (2.56, 2.90)		2.49 (2.33, 2.67)		2.92 (2.73, 3.12)		2.86 (2.53, 3.23)
p-value	<0.001		<0.001		<0.001		<0.001

CI: confidence interval.

Subgroup analyses provided additional insights into specific comparisons. The persistence for rimegepant (75.1%) was significantly higher than that for rizatriptan (55.1%; OR: 2.49, 95%CI 2.33–2.67, p < 0.001) (Table 3, Online Supplementary Figure 2). Similar results were observed for rimegepant (75.6%) versus sumatriptan (51.3%; OR: 2.92, 95%CI 2.73–3.12, p < 0.001). Among patients diagnosed with chronic migraine, persistence for rimegepant was also significantly higher than for oral triptans (78.0% versus 56.0%; OR: 2.86, 95%CI 2.53–3.23, p < 0.001).

The proportion of patients in the pre-matched rimegepant cohort classified as persistent was 77.0%, with the proportion in the pre-matched triptan cohorts ranging from 48.4–54.3% (Online Supplementary Table 2 and Supplementary Figure 2).

Sensitivity analyses confirmed the robustness of these findings across varying durations of follow-up (Table 4). The rimegepant cohort was consistently associated with greater persistence than the oral triptan cohort with six months’ follow-up (OR: 2.72; 95%CI 2.59–2.87, p < 0.001), 18 months’ follow-up (OR: 2.75; 95%CI 2.53–2.98, p < 0.001), or when two claims were required post-index to be considered persistent (OR: 3.26; 95%CI 3.06–3.48, p < 0.001) (Table 4).

Table 4.

Sensitivity analyses.

Outcome	Sensitivity analysis 1: 6-month follow-up		Sensitivity analysis 2: 18-month follow-up		Sensitivity analysis 3: ≥ 2 repeat prescriptions in 12 months
Outcome	Rimegepant(n = 14,266)	Oral triptan(n = 14,266)	Rimegepant(n = 6399)	Oral triptan(n = 6399)	Rimegepant(n = 9909)	Oral triptan(n = 9909)
Proportion of patients persistent, n (%)	9834 (68.93)	6419 (45.00)	5005 (78.22)	3638 (56.85)	6195 (62.52)	3371 (34.02)
Odds ratio (95% CI)	2.72 (2.59, 2.87)		2.75 (2.53, 2.98)		3.26 (3.06, 3.48)
p-value	<0.001		<0.001		<0.001

CI: confidence interval.

The analysis evaluating the impact of a hypothetical unmeasured confounder on the primary outcome association analysis yielded an E-value of 2.69 (i.e., the observed association could only have been caused by residual confounding if the measured covariates had an association ≥2.69 in both treatment cohorts and persistence).

Discussion

Migraine is a prevalent and debilitating condition that affects millions globally, necessitating effective acute treatment options. Understanding treatment persistence is crucial, as it reflects a patient's decision regarding the net benefit of continued use of a given treatment over the long term. This decision is influenced by several factors, including expected effectiveness and clinical utility, tolerability, and risk of MOH. Although triptans are generally efficacious in reducing migraine pain symptoms (28), some patients may experience insufficient response or tolerability issues that affect their experience. For instance, a patient with tolerability issues may choose not to use their triptan if a migraine attack starts during the workday, instead waiting until the evening to treat. This choice to delay treatment can lead to poorer clinical outcomes (29), resulting in low satisfaction and a patient potentially deciding to discontinue the treatment, reflected in reduced persistence. Optimal treatments must first provide a rapid and adequate resolution of symptoms, without tolerability issues and limits on weekly dosage, so that patients are not apprehensive about using treatments early on in an attack onset. These features would simplify the patient's decision to take PRN treatment, leading to higher patient satisfaction, higher persistence, and better overall long-term management of migraine.

The primary finding of this study indicates that patients initiating treatment with rimegepant exhibit significantly higher persistence compared to those using oral triptans. Subgroup analyses further reinforced this, showing that rimegepant was associated with significantly greater persistence than commonly used triptans such as rizatriptan and sumatriptan. Further, these findings were consistent among patients diagnosed with chronic migraine, a more disabled clinical group with more difficult-to-treat migraine. Sensitivity analyses confirmed the robustness of these results across shorter and longer follow-up periods and requiring more frequent refills, indicating that even under different criteria for persistence, rimegepant maintained a significant advantage over oral triptans. Given the evidence supporting rimegepant as an effective and well-tolerated migraine treatment, the authors hypothesize that the higher proportion of persistent patients in the rimegepant cohort may reflect a clinically important difference in patient satisfaction in comparison to the triptan cohort (30), leading to rimegepant users being more likely to continue treatment. This study addresses a critical gap in the literature by providing comparative data on persistence rates between rimegepant and oral triptans, thus informing clinicians and policymakers about treatment options with higher persistence, and more effective overall management of migraine.

The strengths of this study include its large sample size derived from the comprehensive MarketScan claims database, with the number of enrollees during the study period representing over 10% of the US population (∼330 million), which enhances the statistical power of the analyses and the reliability of results. Secondly, the use of PSM allowed for a more balanced comparison between cohorts, addressing potential biases in baseline characteristics, where data were available. Next, we assessed the impact of bias due to unmeasured confounding, finding that a factor would need to be associated with both persistence and the treatment used (rimegepant or triptans) with an OR > 2.69 (“E-value”) to explain the results seen in this study. Based on available literature investigating factors associated with discontinuation of acute triptan use for migraine, the factors with the strongest associations are effectiveness, tolerability, and patient satisfaction, which were not available at baseline for adjustment in the current study (31,32). As such, these factors may mediate persistence, rather than confound, which would be consistent with the authors’ hypothesis that greater persistence associated with rimegepant use may reflect an improved treatment experience for these patients. The inclusion of sensitivity analyses demonstrated consistency across various definitions of persistence and follow-up durations. Additionally, the focus on persistence provides valuable insights into real-world effectiveness beyond the clinical trial setting, highlighting how patients decide to use their prescribed therapies over time in response to their treatment experiences.

This study also has several limitations. First, the analysis was retrospective and relied on previously collected claims data. The data source does not capture all relevant clinical information, including migraine frequency, severity, presence of MOH, treatment effectiveness and tolerability, setting of care, treatment adherence, and reasons for treatment use. Health insurance claims data inherently carry the potential for miscoded or incomplete claims. The use of claims data also dictated the identification of persistence, which relied on observed prescription fills and refills, as claims data cannot capture whether treatments were actually taken or, if taken, the frequency of use. The definition of acute rimegepant use (prescribed quantity of eight tablets on the index date) may have excluded some patients prescribed other tablet quantities despite using rimegepant for acute treatment. However, this definition has been employed previously (25). The definition of acute treatment use also differed between cohorts, relying on a 30-days’ supply for triptan users and a quantity of eight tablets prescribed for rimegepant users. While these definitions were intended to select comparable cohorts of patients with similar acute treatment frequency, the lack of data on treatment indication, compounded by intra- and inter-patient variability in frequency of medication use, makes identification of acute treatment cohorts challenging. PSM was used to balance these cohorts according to the availability of relevant patient characteristics. The approach to measuring persistence in PRN medicines is consistent with ISPOR good practice in using the number of prescriptions over a set time period (26). Here the strength and clarity of this study's results using multiple and stricter sensitivity analyses and in subgroup analysis provides reassurance that results would not change with alternative definitions of persistence. Another limitation of the data source was its inherent exclusion of uninsured patients. Given the sample size of this study, the authors hold the results to be representative of the general population of individuals experiencing migraine. While PSM reduced the effects of confounding factors between cohorts, residual confounding may still exist from unmeasured variables such as migraine severity and/or frequency (e.g., monthly migraine days at index date), lifestyle factors, or patient preferences that could influence treatment persistence. For example, patients are typically prescribed rimegepant after experience with multiple triptans, as recommended in several consensus statements and practice recommendations (1,2,19,20), and therefore rimegepant patients could be further along in the treatment pathway with potentially more severe disease and comorbidities than oral triptan patients (1,33). However, this would bias the results against rimegepant, in that more severely affected patients would be trying it after triptan failure, and the opposite proved true (also see E-value assessment, discussed above). Additionally, the requirement of having ≥12 months of continuous enrollment post-index may have biased the results if duration of eligibility is related to the likelihood of being persistent on treatment. Finally, patients may have been exposed to an intervention prior to the 12-month baseline period, resulting in misclassification as new users. Again, this previous exposure to treatment may indicate greater clinical severity and could potentially bias the comparison against rimegepant.

Conclusions

In this study, patients initiating treatment with rimegepant were significantly more likely to be persistent compared with those starting oral triptans for acute treatment of migraine. This was consistent among those with chronic migraine, and when comparing specific triptans (rizatriptan and sumatriptan). The superior persistence of rimegepant may be a useful marker of patients’ decisions regarding the net benefit of continued PRN use, likely due to its rapid and effective action, consistent benefit across attacks, and good tolerability without negative consequences due to frequency of use. Thus, these findings underscore the potential advantages of rimegepant as a preferred option for acute management of migraine in terms of patient persistence and satisfaction. Article highlights

Patients initiating rimegepant for the acute treatment of migraine were more likely to be persistent on treatment versus those initiating oral triptans.

Persistence results were consistent in subgroup analyses of specific oral triptans versus rizatriptan and sumatriptan) and in patients diagnosed with chronic migraine.

Rimegepant is a favorable treatment option for patients with insufficient response, intolerability, or contraindications to triptans.

Supplemental Material

sj-docx-1-cep-10.1177_03331024251352849 - Supplemental material for A comparison of the persistence of acute treatment with rimegepant versus oral triptans in patients with migraine: A retrospective analysis of US claims data

Supplemental material, sj-docx-1-cep-10.1177_03331024251352849 for A comparison of the persistence of acute treatment with rimegepant versus oral triptans in patients with migraine: A retrospective analysis of US claims data by Stewart J. Tepper, Aaron Jenkins, Carl Henriksen, Feng Dai, Jo Atkinson, Lucy Abraham and Astrid Gendolla in Cephalalgia

Footnotes

Acknowledgements

The authors wish to thank Sally Miller (Broadstreet HEOR) for assisting with medical writing and manuscript submission activities (including all statements and declarations of conflicts of interest and funding), which were funded by Pfizer UK Ltd These activities have been undertaken with the approval of all authors.

Authors’ contributions

All authors 1) made substantial contributions to the concept or design of the work; or acquisition, analysis, or interpretation of data, 2) drafted the article and/or revised it critically for important intellectual content, 3) approved the version to be published, and 4) participated sufficiently in the work to take public responsibility for appropriate portions of the content.

Declaration of conflicting interests

The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: SJT reports financial support from the following: (Research funding) Abbvie, Aeon, Amgen, Annovis, Axsome, Cassava, Cognition, Eli Lilly, Inhibikase, Ipsen, Lundbeck, Merz, Neurolief, Pfizer, PrecisionMed, Revance, Scilex, Suven, UCB; (honoraria from consulting and advisory boards) Abbvie, Aeon, Alphasights, Amgen, Aruene/eNeura, Atheneum, Axsome Therapeutics, Bausch Health, Becker Pharmaceutical Consulting, Catch Therapeutics, ClearView Healthcare Partners, ClickTherapeutics, CoolTech, CRG, Decision Resources, Defined Health, DRG, DocDelta, Dr Reddy's, Eli Lilly, ExpertConnect, FCB Health, Fenix, Gilmartin Capital, GLG, Guidepoint Global, Health Advances, Health Science Communications, HMP Communications, Impel, Initiator Pharma, InteractiveForums, IQVIA, Keyquest, Ki Health Partners, Krog and Partners, Lundbeck, M3 Global Research, Magellan Health, Magnolia Innovation, Miravo Healthcare, MJH Holdings, Neurofront Therapeutics, Neurolief, Nocira, Novartis, P Value Communications, Pain Insights, Inc, Palion Medical, Perfood, Pfizer, Pulmatrix, Putnam Associates, Rehaler, SAI MedPartners, Satsuma, Scilex, Slingshot Insights, Spherix Global Insights, Strategy Inc, Synapse Medical Communication, System Analytic, Taylor and Francis, Tegus, Teva, Theranica, Third Bridge, Tonix, Trinity Partners, Unity HA, Vial, XOC; (salary) Dartmouth-Hitchcock Medical Center, Thomas Jefferson University, Ki Health Partners; (Speakers Bureau) AbbVie, Dr. Reddy's, Eli Lilly, Lundbeck, Pfizer, Scilex, Teva, Tonix; (CME honoraria) American Academy of Neurology, American Headache Society, Annenberg Center for Health Sciences, Catamount Medical Education, Consortium for Research Education Social Awareness and Training In Neurosciences, Diamond Education Foundation, Forefront Collaborative, Haymarket Medical Education, HMP Global, Medical Education Speakers Network, Medical Learning Institute Peerview, Migraine Association of Ireland, Miller Medical Education, National Association for Continuing Education, North American Center for CME, The Ohio State University, Physicians’ Education Resource, PlatformQ Education, Primed, Vindico Medical Education, WebMD/Medscape.

AJ, FD, JA, and LA are employed by and own stock or hold stock options in Pfizer.

CH is a contract programmer for Pfizer.

AG reports financial support for advisory boards, consulting and speaker honoraria from: Grünenthal, Mundipharma, Abbvie/Allergan, Lilly, Teva, Amgen, Novartis, Hormosan, Stada, Lundbeck, Pfizer, Hexal, Esanum, Perfood, Medscape, streamed up, Ärztekammer Nordrhein, Ärztekammer Westfalen Lippe, DGS, Regionalbeauftragte der DMKG.

Funding

The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was sponsored by Pfizer UK Ltd. Medical writing support was provided by Broadstreet HEOR and was funded by Pfizer UK Ltd.

ORCID iDs

Stewart J. Tepper

Aaron Jenkins

Carl Henriksen

Feng Dai

Jo Atkinson

Lucy Abraham

Supplemental material

Supplemental material for this article is available online.

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