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Research · Medication

CGRP migraine drugs

The CGRP antibodies cut about 1.6 migraine days a month more than placebo, a small effect with high certainty. In head-to-head trials, erenumab and atogepant outperformed topiramate with fewer people stopping. Gepants left about 20% pain free 2 hours after an attack against 11% on placebo. Injection site reactions, constipation and nausea were the most frequent side effects.

Add to Bio HackChecked 2026-11-13
Status
Prescription drugs in the US. Erenumab, fremanezumab, galcanezumab and eptinezumab are FDA-approved for preventing migraine in adults, and galcanezumab also for episodic cluster headache. Rimegepant is approved for treating migraine attacks and preventing episodic migraine, ubrogepant for treating attacks only, and atogepant for preventing migraine. None carries a boxed warning.
Also called
CGRP antibodies, anti-CGRP monoclonal antibodies, erenumab, Aimovig, fremanezumab, Ajovy, galcanezumab, Emgality, eptinezumab, Vyepti, gepants, CGRP receptor antagonists, rimegepant, Nurtec ODT, ubrogepant, Ubrelvy, atogepant, Qulipta, calcitonin gene-related peptide
Taken for
migraine prevention, fewer migraine days, chronic migraine, stopping a migraine attack, migraine when triptans are not an option, cluster headache

Strong several reviews agree · Moderate one review or consistent trials · Limited one or a few small studies · Untested no study in people, listed with what it rests on

Shown to help5

Reported risks8

What people take it for, and what was found

Shown to help5

Strong

Preventing migraine with the antibodies

Shown to reduce migraine by about 1.6 days a month more than placebo, a small effect that a meta-analysis rated high certainty.

Compared with placebo injections or infusions [1][2][3]

The numbers and sources
Effect
Across 12 trials, the antibodies reduced monthly migraine days by 1.64 more than placebo (95% CI 1.28 to 1.99), a small effect size (Cohen's d -0.25), with high certainty [1]. A network meta-analysis of 16 trials in episodic migraine found the largest effect for galcanezumab 240 mg (SMD 0.50) and the highest odds of a 50% drop in migraine days for fremanezumab 225 mg (OR 3.17) [2]. In a likelihood to help or harm analysis of phase 3 trials, every antibody dose was more likely to help than to cause stopping for side effects [3].
Population
12 antibody trials in adults [1]; 9,123 participants in 16 trials of episodic migraine [2]; phase 3 trials in episodic and chronic migraine [3].
Sources
[1], [2], [3]
Caveats
Trials mostly ran 3 to 6 months. The rankings between antibodies come from indirect comparison [2].
Moderate

Preventing migraine with gepants

Shown to reduce monthly migraine days with atogepant, with a 50% responder rate about 1.7 times placebo's. Rimegepant every other day cut 0.8 more days than placebo.

Compared with placebo [5][6]

The numbers and sources
Effect
Atogepant reduced monthly migraine days (SMD -0.40, 95% CI -0.46 to -0.34) and acute medication days (SMD -0.45), and raised the share with a 50% drop in migraine days (RR 1.66, 95% CI 1.46 to 1.89), with no added benefit at higher doses [5]. Rimegepant 75 mg every other day reduced monthly migraine days by 4.3 against 3.5 on placebo over weeks 9 to 12 [6].
Population
2,813 adults in 4 atogepant trials [5]; 695 adults with episodic migraine analyzed in one 12-week rimegepant trial [6].
Sources
[5], [6]
Caveats
One meta-analysis for atogepant and one trial for rimegepant prevention.
LimitedVery common

Atogepant against topiramate

One trial found 64% halved their migraine days on atogepant against 39% on topiramate, and 12% stopped for side effects against 30%.

Compared with topiramate at the highest tolerated dose of 50 to 100 mg a day [7]

The numbers and sources
How common
Very common: more than 1 in 10 people.
Effect
Over 24 weeks, 12% on atogepant 60 mg and 30% on topiramate stopped for adverse events (RR 0.4, 95% CI 0.3 to 0.6). A 50% drop in monthly migraine days occurred in 64% against 39% (RR 1.6), and migraine days fell 6.3 against 4.5. One anaphylactic reaction on atogepant was judged drug related [7].
Population
540 adults with at least 4 migraine days a month in 12 countries, 89% women [7].
Sources
[7]
Caveats
One trial. Topiramate's dose was limited to what each person tolerated [7].
StrongVery common

Treating a migraine attack with gepants

Shown to leave about 20% pain free 2 hours after rimegepant or ubrogepant, against 11% to 13% on placebo, about 1 extra pain-free person in 10 treated.

Compared with placebo [8][9][10]; triptans, indirectly [10]

The numbers and sources
How common
Very common: more than 1 in 10 people.
Effect
Two hours after rimegepant 75 mg, 19.8% were pain free against 10.7% on placebo (RR 1.93, number needed to treat 10), and 14.2% against 6.3% stayed pain free through 24 hours (number needed to treat 11) [8]. On ubrogepant, 20.8% were pain free at 2 hours against 12.6% (RR 1.65), and 37.3% against 27.6% were free of their most bothersome symptom [9]. A network meta-analysis found rimegepant and ubrogepant beat placebo, and that most triptans had higher odds of pain freedom than either [10].
Population
6,734 adults in 7 rimegepant trials [8]; 3,326 adults in 3 ubrogepant trials [9]; 46,442 participants in 64 trials [10].
Sources
[8], [9], [10]
Caveats
Each trial treated a single attack. The comparison with triptans was indirect [10].
LimitedVery common

Episodic cluster headache

One trial found galcanezumab 300 mg cut weekly cluster attacks by 8.7 against 5.2 on placebo, with 71% responding against 53%.

Compared with placebo [11]

The numbers and sources
How common
Very common: more than 1 in 10 people.
Effect
Over weeks 1 to 3, weekly cluster headache attacks fell by 8.7 on galcanezumab and 5.2 on placebo, from about 17.5 a week. At week 3, 71.4% against 52.6% had at least a 50% drop in attacks [11].
Population
106 adults with episodic cluster headache, 88 men, in an 8-week trial [11].
Sources
[11]
Caveats
One small trial, described in the label.

Mixed results1

Moderate

Antibodies against older preventive drugs

Mixed results: in one trial erenumab halved migraine days in 55% against 31% on topiramate, but a network analysis found no significant difference from topiramate or divalproex.

Compared with topiramate [4]; topiramate and divalproex, indirectly through placebo [1]; topiramate, propranolol and onabotulinumtoxinA, indirectly [3]

The numbers and sources
Effect
Over 24 weeks, 10.6% stopped erenumab for adverse events against 38.9% on topiramate (OR 0.19, 95% CI 0.13 to 0.27), and 55.4% against 31.2% had at least a 50% drop in monthly migraine days (OR 2.76, 95% CI 2.06 to 3.71) [4]. A network meta-analysis found no significant difference in migraine days between the antibodies and topiramate (WMD -0.19, 95% CI -0.56 to 0.17) or divalproex [1]. The antibodies had higher help-to-harm ratios than propranolol, topiramate or onabotulinumtoxinA [3].
Population
777 adults with at least 4 migraine days a month in Germany [4]; trials of antibodies, topiramate and divalproex [1].
Sources
[4], [1], [3]
Caveats
One head-to-head trial, in which topiramate was dosed to the level each person tolerated [4]. The network comparison was indirect [1].

Doses studied

The labels give erenumab 70 or 140 mg monthly by injection under the skin [12], fremanezumab 225 mg monthly or 675 mg every 3 months [13], galcanezumab 240 mg once then 120 mg monthly for migraine and 300 mg for cluster headache [11], and eptinezumab 100 or 300 mg by intravenous infusion every 3 months [14]. Rimegepant is 75 mg as needed for an attack, or every other day for prevention [6]. Ubrogepant trials used 50 or 100 mg for an attack [15]. Atogepant trials used 10, 30 or 60 mg once daily [16]. The head-to-head trials compared erenumab 70 or 140 mg monthly [4] and atogepant 60 mg daily [7] with topiramate 50 to 100 mg a day.

Risks

Reported risks7

ModerateVery common

Injection site reactions

Shown to raise injection site pain, redness or itching slightly over placebo shots: 18% against 13% on galcanezumab and 43% to 45% against 38% on fremanezumab.

The numbers and sources
How common
Very common: more than 1 in 10 people.
Effect
Injection site reactions occurred in 18% on galcanezumab against 13% on placebo [11], 43% on fremanezumab monthly and 45% quarterly against 38% [13], and 5% to 6% on erenumab against 3% [12]. They were the most frequent reason for stopping fremanezumab (1%) [13].
Population
705 on galcanezumab and 1,451 on placebo [11]; 957 on fremanezumab and 668 on placebo [13]; 1,294 on erenumab and 890 on placebo [12].
Sources
[11], [13], [12]
Caveats
Placebo injections also caused reactions often, so the drug's own share is the gap.
ModerateCommon

Constipation

Shown to raise constipation to 6% to 8% on atogepant against 2%, and to 3% on erenumab 140 mg against 1%. The erenumab label warns of serious cases.

The numbers and sources
How common
Common: between 1 in 100 and 1 in 10 people.
Effect
Constipation occurred in 6% to 8% on atogepant against 2% on placebo [16], and pooled atogepant trials found it more than twice as frequent (RR 2.55, 95% CI 1.91 to 3.41) [5]. On erenumab it occurred in 3% at 140 mg and 1% at 70 mg against 1% [12]. The erenumab label reports constipation with serious complications after approval, some needing hospital care or surgery, mostly after the first dose [12].
Population
1,403 on atogepant and 663 on placebo [16]; 2,813 in 4 atogepant trials [5]; erenumab trials and postmarketing reports [12].
Sources
[16], [5], [12]
Caveats
The label states drugs that slow the gut may add to the risk [12].
ModerateCommon

Nausea and tiredness with gepants

Shown to raise nausea on gepants, 9% on atogepant 60 mg against 3%, and 2% to 4% on rimegepant or ubrogepant against under 1% to 2%.

The numbers and sources
How common
Common: between 1 in 100 and 1 in 10 people.
Effect
On atogepant, nausea occurred in 5% to 9% against 3%, fatigue or sleepiness in 4% to 5% against 4%, and decreased appetite in up to 3% [16]. Pooled atogepant trials found nausea (RR 2.19) and fatigue at high doses (RR 3.07) more frequent [5]. On ubrogepant, nausea occurred in 2% to 4% against 2% and sleepiness in 2% to 3% against 1% [15]. In the rimegepant prevention trial, nausea occurred in 2.7% against 0.8% [6]. Adverse events overall after a rimegepant dose were 14.3% against 12.7% (RR 1.14, 95% CI 1.00 to 1.30) [8].
Population
Label trials [16][15][6]; 2,813 in atogepant trials [5]; 6,734 in rimegepant trials [8].
Sources
[16], [5], [15], [6], [8]
Caveats
Short trials.
LimitedCommon

Allergic reactions

Limited evidence: allergic reactions occurred in 1% to 2% on eptinezumab against none on placebo. Labels report rash, swelling and anaphylaxis after approval.

The numbers and sources
How common
Common: between 1 in 100 and 1 in 10 people.
Effect
Hypersensitivity reactions, such as itching and flushing on the day of infusion, occurred in 1% on eptinezumab 100 mg and 2% on 300 mg against 0% [14]. The erenumab label reports rash, angioedema and anaphylaxis after approval, some more than a week after a dose [12]. The ubrogepant label lists anaphylaxis and facial or throat swelling and contraindicates it after a serious reaction [15]. One anaphylactic reaction occurred on atogepant in a trial [7].
Population
1,153 on eptinezumab and 588 on placebo [14]; postmarketing reports [12][15]; 273 on atogepant [7].
Sources
[14], [12], [15], [7]
Caveats
The band above is the eptinezumab trial rate.
LimitedCommon

Weight loss on atogepant

The atogepant label reports a weight drop of 7% or more in 5.3% on 60 mg against 2.5% on placebo.

The numbers and sources
How common
Common: between 1 in 100 and 1 in 10 people.
Effect
A weight decrease of at least 7% at any point occurred in 2.5% on placebo, 3.8% on 10 mg, 3.2% on 30 mg and 5.3% on 60 mg [16].
Population
1,403 on atogepant and 663 on placebo in three trials [16].
Sources
[16]
Caveats
Label figures from 12-week trials.
LimitedHow often is not known

Raynaud's phenomenon

Case reports: the labels describe new or worse Raynaud's phenomenon after approval, a median 71 days after an antibody dose, sometimes serious.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
New, recurrent or worsening Raynaud's phenomenon was reported after CGRP antagonists, with onset a median 71 days after an antibody dose. Many cases had serious outcomes, including hospitalization and disability from pain, and most resolved after stopping [12]. The fremanezumab and eptinezumab labels carry the same warning [13][14].
Population
Postmarketing reports [12].
Sources
[12], [13], [14]
Caveats
No denominator.
LimitedHow often is not known

Gepant levels with other drugs

The labels state strong CYP3A4 inhibitors such as clarithromycin raise gepant levels up to almost tenfold, and inducers such as rifampin cut them about 80%.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
Ketoconazole raised ubrogepant exposure 9.7-fold, and the label contraindicates ubrogepant with strong CYP3A4 inhibitors such as ketoconazole, itraconazole and clarithromycin. Verapamil raised exposure about 3.5-fold, and dose changes apply with moderate inhibitors such as cyclosporine, ciprofloxacin, fluconazole, fluvoxamine and grapefruit juice. Rifampin cut exposure 80%, and the label advises against use with phenytoin, barbiturates, rifampin or St. John's Wort [15]. Itraconazole raised rimegepant exposure 4-fold and rifampin cut it 80% [6]. The atogepant label lowers the dose with strong CYP3A4 inhibitors [16].
Population
Drug interaction studies described in labeling [15][6][16].
Sources
[15], [6], [16]
Caveats
Changes in drug levels, not measured harm.

Mixed results1

ModerateHow often is not known

High blood pressure

Mixed results: labels report new or worse high blood pressure after approval, while two meta-analyses found no significant rise in blood pressure or hypertension.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
The erenumab label reports new and worsening hypertension after approval, some needing medicine or hospital care, most often within 7 days of a dose [12]. The galcanezumab and atogepant labels carry the same warning for CGRP antagonists [11][16]. Across 19 randomized trials, hypertension did not rise against control (RR 0.91, 95% CI 0.58 to 1.43), in very low certainty evidence [17]. Before and after erenumab, systolic (MD 0.86 mmHg) and diastolic pressure (MD 1.33 mmHg) did not change significantly [18].
Population
Postmarketing reports [12]; 19 trials in adults with migraine [17]; studies of erenumab users [18].
Sources
[12], [11], [16], [17], [18]
Caveats
Trials enrolled relatively healthy people for short periods [17]. The before-and-after studies were fragile and heterogeneous [18].

Possible, not studied in people1

Untested

Pregnancy

Not studied in people. Animal studies found no harm to monkey offspring from erenumab, and lower fetal weight in rats at high gepant doses.

No study in people. This rests on animal studies.

The numbers and sources
Effect
The labels state there are no adequate data in pregnant women. No adverse effects on offspring were seen when pregnant monkeys received erenumab at exposures above human levels [12]. Rimegepant lowered fetal weight and raised skeletal variations in rats at exposures above clinical levels with maternal toxicity [6], and atogepant lowered fetal weight and bone formation in rats at the two highest doses [16].
Population
Pregnant monkeys and rats (animal) [12][6][16].
Sources
[12], [6], [16]
Caveats
Animal data do not show what happens in human pregnancy.

Claims tested and not found

  1. That gepants relieve a migraine attack better than triptans. In a network meta-analysis of 64 trials, most triptans had higher odds of pain freedom at 2 hours than rimegepant (OR 1.58 to 3.13) or ubrogepant (OR 1.54 to 3.05) [10].
  2. That higher doses of atogepant prevent more migraines. Pooled trials found no dose-related improvement between doses [5].
  3. That CGRP-targeted drugs raise blood pressure in trials. Hypertension did not rise against control across 19 randomized trials (RR 0.91) [17].

Related

Triptans

Sources

  1. Robblee J, Hakim SM, Reynolds JM, et al. Nonspecific oral medications versus anti-calcitonin gene-related peptide monoclonal antibodies for migraine: A systematic review and meta-analysis of randomized controlled trials. Headache. 2024. https://doi.org/10.1111/head.14693
  2. Shakir I, Shahzad F, Shabbir A, et al. Efficacy and safety of CGRP monoclonal antibodies for migraine prevention in episodic migraine; a network Meta-analysis. European Journal of Clinical Pharmacology. 2026. https://doi.org/10.1007/s00228-025-03934-3
  3. Drellia K, Kokoti L, Deligianni CI, et al. Anti-CGRP monoclonal antibodies for migraine prevention: A systematic review and likelihood to help or harm analysis. Cephalalgia. 2021. https://doi.org/10.1177/0333102421989601
  4. Reuter U, Ehrlich M, Gendolla A, et al. Erenumab versus topiramate for the prevention of migraine: a randomised, double-blind, active-controlled phase 4 trial. Cephalalgia. 2022. https://doi.org/10.1177/03331024211053571
  5. Hou M, Luo X, He S, et al. Efficacy and safety of atogepant, a small molecule CGRP receptor antagonist, for the preventive treatment of migraine: a systematic review and meta-analysis. The Journal of Headache and Pain. 2024. https://doi.org/10.1186/s10194-024-01822-2
  6. U.S. Food and Drug Administration. NURTEC ODT (rimegepant) orally disintegrating tablets, prescribing information. 2026. DailyMed. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9ef08e09-1098-35cc-e053-2a95a90a3e1d
  7. Reuter U, Dycke AV, Versijpt J, et al. Tolerability, safety, and efficacy of atogepant versus topiramate in adults with migraine (TEMPLE): a randomised, head-to-head, phase 3b trial. The Lancet Neurology. 2026. https://doi.org/10.1016/S1474-4422(26)00214-0
  8. Istoc M, Chaudhry BA, Christensen RH, et al. Rimegepant for the acute treatment of migraine: a systematic review and meta-analysis. The Journal of Headache and Pain. 2026. https://doi.org/10.1186/s10194-026-02388-x
  9. Yang Y, Chen M, Sun Y, et al. Safety and Efficacy of Ubrogepant for the Acute Treatment of Episodic Migraine: A Meta-Analysis of Randomized Clinical Trials. CNS Drugs. 2020. https://doi.org/10.1007/s40263-020-00715-7
  10. Yang CP, Liang CS, Chang CM, et al. Comparison of New Pharmacologic Agents With Triptans for Treatment of Migraine: A Systematic Review and Meta-analysis. JAMA Network Open. 2021. https://doi.org/10.1001/jamanetworkopen.2021.28544
  11. U.S. Food and Drug Administration. EMGALITY (galcanezumab) injection, prescribing information. 2026. DailyMed. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=33a147be-233a-40e8-a55e-e40936e28db0
  12. U.S. Food and Drug Administration. AIMOVIG (erenumab) injection, prescribing information. 2026. DailyMed. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b998ed05-94b0-47fd-b28f-cddd1e128fd8
  13. U.S. Food and Drug Administration. AJOVY (fremanezumab) injection, prescribing information. 2026. DailyMed. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=98e344ea-5916-4947-b6f2-4a76ccc04b6b
  14. U.S. Food and Drug Administration. VYEPTI (eptinezumab) injection, prescribing information. 2026. DailyMed. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=79065861-6aa5-4d1f-829f-3a6471286b36
  15. U.S. Food and Drug Administration. UBRELVY (ubrogepant) tablets, prescribing information. 2026. DailyMed. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=fd9f9458-fd96-4688-be3f-f77b3d1af6ab
  16. U.S. Food and Drug Administration. QULIPTA (atogepant) tablets, prescribing information. 2026. DailyMed. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8c8ab8f4-32bd-497a-befa-70c8a51d8d52
  17. Kim K, Kim K, Cho SY, et al. Risk of hypertension after CGRP antagonist treatment in migraine: A systematic review and meta-analysis. Headache. 2026. https://doi.org/10.1111/head.70148
  18. Makita LM, de Kleimmann RF, de Oliveira RR, et al. Assessing blood pressure changes and hypertension-related outcomes in patients with migraine treated with erenumab: A systematic review and meta-analysis. Headache. 2025. https://doi.org/10.1111/head.14921

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