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COURAGE

Real-World Use of Ubrogepant as Acute Treatment for Migraine with an Anti-Calcitonin Gene-Related Peptide Monoclonal Antibody: Results from COURAGE

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Year of Publication: 2024

Authors: Richard B. Lipton, Janette Contreras-De Lama, Daniel Serrano, ..., Aubrey Manack Adams

Journal: Neurology and Therapy

Citation: Neurol Ther. 2024;13:69–83. doi:10.1007/s40120-023-00556-8

Link: https://doi.org/10.1007/s40120-023-00556-8

PDF: https://pmc.ncbi.nlm.nih.gov/articles/PM...Article_556.pdf

Clinical Question

Is ubrogepant effective and satisfying as an acute migraine treatment when used with anti-CGRP mAbs, with or without onabotulinumtoxinA, in real-world settings?

Study Overview

Objective

To evaluate the real-world effectiveness, satisfaction, and treatment optimization of ubrogepant for acute migraine when used with anti-CGRP monoclonal antibodies, with or without onabotulinumtoxinA.

Study Summary

Ubrogepant with anti-CGRP mAbs showed high rates of pain relief and functional recovery
Meaningful pain relief was achieved in ~80% at 4 hours post-dose
Over 70% of users were satisfied with treatment

Intervention

App-based, prospective observational study using Migraine Buddy over 30 days; included patients using ubrogepant (50 or 100 mg) with anti-CGRP mAbs, with/without onabotulinumtoxinA.

Patients per Arm

245 and 69

Bottom Line

Ubrogepant demonstrated high real-world effectiveness, functional recovery, and user satisfaction when used with anti-CGRP mAbs, with or without Botox.

        Major Points
        Prospective, real-world, app-based (Migraine Buddy) observational study conducted Sept 2020 – April 2021 in US adults; analyzed 245 ubrogepant + anti-CGRP mAb users and 69 ubrogepant + anti-CGRP mAb + onabotulinumtoxinA users.
First-attack Meaningful Pain Relief (MPR): mAb-only 61.6% (151/245) at 2h and 80.4% (197/245) at 4h; mAb+Botox 63.8% (44/69) at 2h and 84.1% (58/69) at 4h.
First-attack Return to Normal Function (RNF): mAb-only 34.7% (85/245) at 2h and 55.5% (136/245) at 4h; mAb+Botox 39.1% (27/69) at 2h and 55.1% (38/69) at 4h.
Across up to 10 treated attacks (1153 attacks mAb-only; 347 attacks mAb+Botox), MPR at 4h was 73.5% and 66.6%; RNF at 4h was 53.2% and 48.4% — response remained stable across repeated attacks.
Treatment satisfaction with ubrogepant: 72.7% (168/231) mAb-only and 68.8% (44/64) mAb+Botox; satisfaction with ubrogepant plus current preventive: 58.9% mAb-only and 59.4% mAb+Botox.
Acute treatment optimization (mTOQ-4 ≥4): 79.7% (184/231) mAb-only and 78.1% (50/64) mAb+Botox; mean mTOQ-4 5.6 (mAb-only) and 5.4 (mAb+Botox).
No systematic adverse-event collection (real-world observational design); safety was not a study endpoint.
Ubrogepant is an oral small-molecule CGRP receptor antagonist (gepant class) FDA-approved for acute migraine treatment.
Design rationale: anti-CGRP mAb 'wearing off' and incomplete CGRP-pathway coverage motivate use of an acute gepant in patients already on CGRP-directed prevention.
Funded by Allergan/AbbVie; the ubrogepant + onabotulinumtoxinA-only arm was reported separately (Manack Adams 2023, J Headache Pain).

      

Design

Study Type: Prospective, observational, app-based study

Randomization:

Blinding: Unblinded (open-label)

Enrollment Period: September 2020 – April 2021

Follow-up Duration: 30 days

Countries: USA

Sample Size: 314

Analysis: Descriptive statistics; generalized linear models with binomial distribution and logit link for first-attack, satisfaction and mTOQ endpoints; repeated-attack diary endpoints via GEE; up to first 10 treated attacks per participant. Recruitment was app-based from the Migraine Buddy user population (no traditional clinical center count).

Inclusion Criteria

US adult Migraine Buddy app users
≥3 migraine attacks in past 30 days
Prior treatment of ≥3 attacks with ubrogepant 50 or 100 mg
Current use of anti-CGRP mAb, onabotulinumtoxinA, or both, for migraine prevention
Plan to continue preventive treatment

Exclusion Criteria

No diary data on treated attacks (26 of 271 excluded in mAb arm; 10 of 79 excluded in mAb+Botox arm)

Baseline Characteristics

Age - mAb only: Mean 41.2 ± 10.8 years

Age - mAb + Botox: Mean 43.8 ± 10.1 years

Female - mAb only: 89.0% (218/245)

Female - mAb + Botox: 89.9% (62/69)

White race - mAb only: 83.1% (192; denominator = participants with nonmissing race data, not full n=245)

White race - mAb + Botox: 84.4% (54; denominator = participants with nonmissing race data, not full n=69)

MIDAS IVa or IVb: 87.3% (mAb only), 94.2% (mAb + Botox)

PHQ-4: Mean 8.0 ± 2.9 (both arms)

Ubrogepant 100 mg: 58.4% (mAb only), 53.6% (mAb + Botox)

Anti-CGRP mAb - erenumab: 44.5% (mAb only), 43.5% (mAb + Botox)

Anti-CGRP mAb - galcanezumab: 35.1% (mAb only), 30.4% (mAb + Botox)

Anti-CGRP mAb - fremanezumab: 18.0% (mAb only), 23.2% (mAb + Botox)

Anti-CGRP mAb - eptinezumab: 2.9% (mAb only), 2.9% (mAb + Botox)

Arms

Field	Ubrogepant + anti-CGRP mAb	Ubrogepant + anti-CGRP mAb + onabotulinumtoxinA
Intervention	Ubrogepant 50 or 100 mg as needed for acute migraine, while on anti-CGRP monoclonal antibody preventive	Ubrogepant 50 or 100 mg as needed for acute migraine, on anti-CGRP mAb plus onabotulinumtoxinA
Duration	30-day observational period	30-day observational period

Outcomes

Outcome	Type	Intervention
No formal primary vs secondary hierarchy was designated. The paper's prespecified effectiveness endpoints were: Meaningful Pain Relief (MPR) and Return to Normal Function (RNF) at 2 and 4 hours post-dose (first attack and across up to 10 treated attacks), plus treatment satisfaction and acute treatment optimization (mTOQ-4) at 30 days. First endpoint presented: MPR at 2 and 4 hours post-dose (first treated attack).	Primary	mAb only: 2h 61.6% (151/245; 95% CI 55–68), 4h 80.4% (197/245; 95% CI 75–85). mAb + Botox: 2h 63.8% (44/69; 95% CI 52–74), 4h 84.1% (58/69; 95% CI 73–91).
Return to Normal Function (RNF) at 2 and 4 hours (first treated attack) — prespecified effectiveness endpoint (no formal secondary designation)	Secondary	mAb only: 2h 34.7% (85/245; 95% CI 29–41), 4h 55.5% (136/245; 95% CI 49–62). mAb + Botox: 2h 39.1% (27/69; 95% CI 28–51), 4h 55.1% (38/69; 95% CI 43–66).
MPR across up to 10 treated attacks	Secondary	mAb only (N=1153 attacks): 2h 51.3% (592/1153; 95% CI 48–54), 4h 73.5% (847/1153; 95% CI 71–76). mAb + Botox (N=347 attacks): 2h 49.6% (172/347; 95% CI 44–55), 4h 66.6% (231/347; 95% CI 62–72).
RNF across up to 10 treated attacks	Secondary	mAb only: 2h 32.2% (371/1153; 95% CI 29–35), 4h 53.2% (613/1153; 95% CI 50–56). mAb + Botox: 2h 30.8% (107/347; 95% CI 26–36), 4h 48.4% (168/347; 95% CI 43–54).
Treatment satisfaction with ubrogepant (satisfied/very satisfied/extremely satisfied on 7-pt scale)	Secondary	72.7% (168/231) mAb only; 68.8% (44/64) mAb + Botox
Satisfaction with ubrogepant in combination with current preventive	Secondary	58.9% (136/231) mAb only; 59.4% (38/64) mAb + Botox
Acute treatment optimization (mTOQ-4 score ≥4)	Secondary	79.7% (184/231) mAb only; 78.1% (50/64) mAb + Botox
Serious treatment-emergent adverse events	Adverse	Not systematically collected in COURAGE (real-world observational design)
TEAEs leading to discontinuation	Adverse	Not systematically collected in COURAGE (real-world observational design)
Any TEAE	Adverse	Not systematically collected in COURAGE (real-world observational design)

Subgroup Analysis

No formal subgroup efficacy comparisons; descriptive summaries across two arms (mAb only vs mAb + Botox)

Criticisms

Self-reported, app-based data with no clinician confirmation of migraine diagnosis
No placebo or control arm
Short 30-day observation window
No systematic collection of adverse events
Selection bias: only Migraine Buddy users with digital access included
Ubrogepant-only comparator not evaluated in this analysis (separate mAb-only-vs-combo comparisons not statistically tested)
Unadjusted models reported; potential residual confounding by preventive regimen and severity

Funding

Funded by Allergan (prior to acquisition by AbbVie); authors affiliated with AbbVie, OPEN Health, Healint, or Critical Path Institute

Based on: COURAGE (Neurology and Therapy, 2024)