Nurtec® (rimegepant) in real-world clinical practice
Consistency of response, difficult-to-treat patients and treatment persistence: findings from HeAD-US, CONFIDENCE, GAINER, AAN 2025 congress materials and a persistence analysis
4+
real-world studies
1570
patients in HeAD-US
2169
attacks in CONFIDENCE
80.4%
pain freedom at 2 h with early intake (GAINER)
Audio digest
The key findings of this digest as a two-host podcast (~4 min)
Background
Why real-world evidence matters
Randomised trials established the efficacy of rimegepant for the acute treatment of migraine, yet several questions that matter in the clinic fall outside the design of an RCT.
Will it work again?
Consistency of response from attack to attack → CONFIDENCE
What about difficult patients?
Chronic migraine, failed preventives, poor triptan response → GAINER
What if the dose is late?
Effect with «imperfect» timing of intake → GAINER
Will patients stay on therapy?
12-month persistence → US claims analysis
Cross-sectional study · US
HeAD-US: gepants and triptans head-to-head
Digital platform Migraine Buddy, 1570 patients on monotherapy: triptans (n=1003) or gepants (n=567). The gepant group was «sicker» at baseline — more chronic migraine (38% vs 28%) and more preventive use (82% vs 71%) — the typical real-world pattern of gepants prescribed after triptan failure.
Gepants (n=567)
Triptans (n=1003)
Adjusted predicted response probabilities, % (marginal standardisation; adjusted for age, sex, severity, headache frequency, preventive use, etc.)
aOR 1.04
pain freedom at 2 h — comparable between classes
95% CI 0.84–1.30
aOR 1.36
pain relief at 24 h — advantage of gepants
95% CI 1.09–1.71
Congress materials
AAN 2025: satisfaction and treatment optimisation
Rimegepant
Triptans
NHWS: p<0.001. Adelphi DSP (US, 2022): optimised acute treatment per mTOQ-6.
Prospective observational study · US
CONFIDENCE: «Will it work again?» — consistency of response
2169 attacks in 416 patients, 28 days of daily e-diaries (median 7 attacks per patient). A complex population: 84% on preventives (34% anti-CGRP mAbs and 34% botulinum toxin), 89% had previously discontinued at least one triptan.
61.3%
of all attacks — meaningful pain relief ≤2 h
57.6%
of all attacks — meaningful improvement in functioning ≤2 h
68.4%
of all attacks — satisfaction with treatment
Outcomes hold steady from attack to attack
Pain relief ≤2 h
Functioning ≤2 h
Satisfaction
% of attacks achieving the outcome; attacks 1–4 (n=416/389/348/289).
Within-patient consistency
≥2 of first 3 attacks (n=349)
≥3 of first 4 attacks (n=289)
About 2 in 3 patients had meaningful pain relief in ≥2 of their first 3 attacks; 74% were satisfied with treatment in ≥2 of 3 attacks. A predictable result simplifies treatment selection and supports adherence.
Prospective multicentre study · Italy
GAINER: difficult-to-treat patients of headache centres
16 headache centres
n=103
CM — 24% of the sample
mean 2.7 failed preventive classes
57% had absent or poor triptan response
The first real-world data on rimegepant in chronic migraine (44% of CM patients had medication overuse). Pain freedom at 2 hours was achieved by 44.7% — higher than in RCTs (19–21%), reflecting the open-label design and the population; pain relief by 70.9%.
Share of patients pain-free after rimegepant 75 mg ODT
80.4%
of patients achieved complete headache freedom at 2 hours when rimegepant was taken within the first 60 minutes of attack onset (p=0.032)
64.1%
pain-free at 24 h without rescue
19.4%
needed rescue medication
The effect was independent of prior triptan response (p=0.816) and baseline attack severity (p=0.316).
The patient voice
7.1/10
global treatment satisfaction
85.4%
rated tolerability good/excellent
15.5%
adverse events — all mild and self-limiting
48.3%
24.1%
27.6%
Comparison with prior triptan experience (patient-rated, n=87): better / comparable / worse.
Retrospective claims analysis · US
Persistence: satisfaction converts into behaviour
MarketScan 2019–2023, PSM-matched cohorts of 9909 patients each. Persistence — ≥1 repeat dispensing within 12 months.
Odds ratio of staying on therapy (rimegepant vs oral triptans), 95% CI.
The odds of staying on rimegepant were 2.7-fold higher than on oral triptans (OR 2.72; 95% CI 2.56–2.90); the result was consistent across all subgroups, including chronic migraine.
Randomised confirmation
When triptans are unsuitable: the phase 4 RCT
n=585
failure of ≥2 triptans — 84.9%
intolerance — 30.5%
contraindications — 9.1%
Rimegepant 75 mg
Placebo
Difference 23.2% (95% CI 15.3–31.1); p<0.0001. All 10 key secondary endpoints met. Placebo-level tolerability: AE 12.5% vs 12.1%.
Summary
What the real-world data show
- ✓High treatment satisfaction — 68–74% in CONFIDENCE; 71% vs 52% on triptans (NHWS); 7.1/10 in GAINER
- ✓Consistent response from attack to attack — steady outcomes across attacks 1–4; 65% had relief in ≥2 of 3 attacks (CONFIDENCE)
- ✓Recovery of functioning — functioning improved ≤2 h in 58% of attacks (CONFIDENCE); full recovery in 48% (GAINER)
- ✓Sustained effect to 24 h — gepant advantage in 24-h relief: aOR 1.36 (HeAD-US); 64% pain-free at 24 h without rescue (GAINER)
- ✓Value in patients with inadequate triptan response — 87% vs 62% — optimised treatment (Adelphi DSP); effect independent of prior triptan response (GAINER)
Real-world evidence complements the RCTs: a consistent, predictable response, clinically meaningful results in difficult-to-treat patients and with late dosing, high satisfaction and greater treatment persistence. The findings point to potential advantages of rimegepant in clinical practice.
Limitations
Methodological notes
HeAD-US
Class-level comparison (gepants vs triptans), no per-molecule breakdown; cross-sectional self-report; likely channelling of «sicker» patients to gepants. The significant advantage was for 24-h relief only.
AAN 2025
Congress abstracts (Adelphi DSP, NHWS): descriptive analyses without full publications; wording — «patients reported higher satisfaction», no claims of superior efficacy.
CONFIDENCE
No comparator arm; experienced rimegepant users (responder selection likely); tolerability not systematically collected; descriptive statistics.
GAINER
n=103, no placebo control; the drug was not reimbursed — possible selection of difficult-to-treat headache-centre patients; the triptan comparison is a retrospective patient rating.
Literature
References
- Teichrow D, Khorsand B, Fanning KM, et al. Comparative analysis of real-world acute prescription migraine therapy outcomes: insights from the HeAD-US study. Headache. 2026;66:1537-1547. doi:10.1111/head.70113
- Lipton RB, Abraham L, Urani A, et al. Consistency of response to rimegepant for the acute treatment of migraine among real-world users — findings from the prospective observational CONFIDENCE study. J Headache Pain. 2026;27:200. doi:10.1186/s10194-026-02421-z
- Iannone LF, Vaghi G, Sebastianelli G, et al. Effectiveness and tolerability of rimegepant in the acute treatment of migraine: a real-world, prospective, multicentric study (GAINER study). J Headache Pain. 2025;26:4. doi:10.1186/s10194-024-01935-8
- Tepper SJ, Jenkins A, Henriksen C, et al. A comparison of the persistence of acute treatment with rimegepant versus oral triptans in patients with migraine: a retrospective analysis of US claims data. Cephalalgia. 2025;45(7):3331024251352849. doi:10.1177/03331024251352849
- Lipton RB, et al. Treatment outcomes in people with migraine receiving rimegepant or triptans: a descriptive analysis from a real-world survey. AAN 2025, abstr. P1-12.008 (Adelphi Migraine DSP); Dagenais S, et al. AAN 2025 (NHWS 2023). Neurology. 2025. doi:10.1212/WNL.0000000000210468
- Ashina M, McAllister P, Gaul C, et al. Rimegepant for acute treatment of migraine in triptan-unsuitable adults: a randomized, double-blind, placebo-controlled phase 4 trial. Cephalalgia. 2025;45(11). doi:10.1177/03331024251395298
Prepared for informational purposes from published data; full study limitations are given under «Methodological notes».