- ACRONYMS AND DEFINITIONS
- ACP - American College of Physicians
- AAFP - American Academy of Family Physicians
- AAN - American Academy of Neurology
- AAP - American Academy of Pediatrics
- AHS - American Headache Society
- CGRP - Calcitonin gene-related peptide
- IHS - International Headache Society
- MBS - Most bothersome symptom
- EPIDEMIOLOGY
- In the overall U.S. adult population, 18% of women and 6% of men report at least one migraine attack in the last year. The prevalence of migraine headaches increases until the age of 40 years reaching a peak of around 40% in women and 10% in men, after which, it steadily declines. Asians have the lowest prevalence, blacks have an intermediate prevalence, and whites have the highest prevalence. [7]
- In children, the prevalence of migraine headache is 1% – 3% for 3 to 7 years old, 4% – 11% for 7 to 11 year olds, and 8% – 23% by age 15 years. The average age of onset is 7.2 years in boys and 10.9 years in girls [10,11,22]
- PATHOPHYSIOLOGY
- The pathophysiology of migraine headache is complex and not completely understood
- Briefly, it is believed that a migraine headache is initiated by the release of vasoactive peptides from sensory neurons that innervate meningeal blood vessels. The peptides stimulate arterial dilation in the meninges, and at the same time, activate perivascular trigeminal nerves. Trigeminal nerve activation leads to brain stem stimulation.
- Brain stem stimulation ascends to the thalamus and the cortex causing heightened sensitivity to pain and stimulation
- The auras that precede some migraines are thought to occur from a slow wave of oligemia (reduced blood flow) that crosses the cerebral cortex [1,8]
- DIAGNOSTIC CRITERIA
- Overview
- Migraine headaches are typically divided into two classes - Migraine without aura and Migraine with aura
- The International Headache Society publishes the most widely accepted criteria for migraine headaches. The criteria are detailed below.
IHS Migraine Without Aura Criteria |
---|
A. At least five attacks fulfilling criteria B, C, and D |
B. Headache attacks lasting 4 - 72✝ hours (untreated or unsuccessfully treated) |
C. Headache has at least 2 of the following 4 characteristics:
|
D. At least one of the following during headache:
|
IHS Migraine With Aura Criteria |
---|
Migraine headache with aura is a migraine headache (see above) that is preceded by the following: |
A. At least 2 attacks fulfilling criteria B and C |
B. One or more of the following fully reversible aura symptoms:
|
C. At least 2 of the following 4 characteristics:
|
- TRIGGERS
MIGRAINE TRIGGERS |
---|
Food triggers
|
Physiologic triggers
|
Environmental triggers
|
- MIGRAINE AND ATRIAL HEART DEFECTS
- Patent foramen ovale (PFO)
- The foramen ovale is a hole between the atria that allows right-to-left shunting of blood in utero. After birth, when blood circulation assumes its normal physiology, the foramen ovale closes by the age of one year in most individuals.
- In up to 35% of the population, the foramen ovale does not completely close, and it becomes what is called a "patent foramen ovale"
- Some observational studies have found that patients with a PFO are at higher risk of migraine headaches, particularly migraine with aura. Other studies have not found a significant association.
- Proposed mechanisms of the link include: shunting of migraine triggering agents from right-to-left that normally would have been removed in the lungs; sudden hypoxemia from periodic right-to-left shunting
- Observational studies have found that PFO closure improves migraine in some patients
- A randomized, controlled trial (the MIST trial) was performed that compared PFO closure with sham closure in patients with intractable migraines with aura. The study found no significant effect of PFO closure on the primary outcome of migraine cessation. [PMID 18316488]
- Based on the available evidence, there is no conclusive evidence that PFO increases the risk of migraine or that PFO closure reduces migraine [18,19]
- Atrial septal defects (ASD)
- Atrial septal defects occur when the septum between the atria of the heart fails to develop correctly leaving a defect (hole) between the atria. Atrial septal defects typically cause left-to-right shunting of blood.
- Much like patent foramen ovale, ASDs have been associated with migraine headaches in observational studies. ASD closure has also been shown to improve migraine symptoms in some patients.
- Paradoxically, ASD closure has been associated with new-onset migraines in patients who never had migraine headaches. In some studies, up to 17% of patients who never had a migraine experienced new-onset migraine headaches within 2 months of having an ASD closed. [19, 20]
- A randomized controlled trial published in the JAMA in 2015 found that the addition of clopidogrel (75 mg/day for 3 months) to aspirin following ASD closure significantly reduced the number of days with migraine (0.4 vs 1.4) and the incidence of new-onset migraine (9.5% vs 21.8%) in the 3 months after closure. [PMID 26551304]
- ACUTE TREATMENT
- Adults
- The American Academy of Neurology issued migraine treatment guidelines in 2000. The American Academy of Family Physicians and the American College of Physicians (AAFP/ACP) issued joint guidelines in 2002. The guidelines are very similar, and the AAFP/ACP guidelines are presented below.
- Since the publication of these guidelines, several new classes of drugs (e.g. CGRP receptor antagonists, 5-HT1F agonists) have become available. No guidelines have been published since the advent of these medications, so they are not addressed.
AAFP/ACP Adult Migraine Treatment Recommendations |
---|
First-line therapies
|
Second-line therapies
|
- Children and adolescents
- The AAN published guidelines for the treatment of acute migraine in children in 2019. Those guidelines along with information from trials and other sources are presented in the table below.
Migraine treatment recommendations in children and adolescents |
---|
Children (4 - 11 years old)
|
Adolescents (≥ 12 years old)
|
- Pregnancy
- There are no consensus guidelines for treating migraines in pregnancy. Further complicating the matter, drug safety data is largely from observational studies.
- In general, 60 - 70% of women see an improvement in their migraine headache symptoms during pregnancy. Up to 20% see their migraines disappear. [12]
- The tables below summarizes the current available safety information for migraine medications in pregnancy and nursing
Migraine Medications in Pregnancy | |
---|---|
Medication | Comment |
Acetaminophen |
|
Aspirin |
|
Ibuprofen Naproxen |
|
Caffeine |
|
Triptans |
|
Ergotamines |
|
Migraine Medications in Nursing | |
---|---|
Medication | Comment |
Acetaminophen |
|
Aspirin |
|
Ibuprofen Naproxen |
|
Caffeine |
|
Triptans |
|
Ergotamines |
|
- PREVENTIVE TREATMENT
- Adults
- Medication recommendations from the AAN and the AHS are presented in the table below along with criteria for preventive therapy from the AAFP and ACP
- Since the guidelines were published, several new classes of migraine medications have become available (e.g. CGRP inhibitors). No guidelines have been published since the advent of these medications, so they are not addressed.
- In general, preventive medication is recommended for patients who meet any of the following criteria:
- Two or more attacks per month that produce disability that lasts 3 or more days per month
- Contraindication to, or failure of, acute treatments
- Use of abortive medication more than twice per week
- The presence of uncommon migraine conditions, including hemiplegic migraine, migraine with prolonged aura, or migrainous infarction [9]
Medications that are proven effective in preventing migraines in adults | |
---|---|
Medication | Dosing |
Valproic acid (Depakote®) |
|
Topiramate (Topamax®) |
|
Propranolol (Inderal®) |
Standard-release
|
Metoprolol (Toprol®) |
|
Timolol |
|
Petasites (butterbur plant extract) |
|
CGRP inhibitors |
|
Medications that are probably effective in preventing migraines in adults | |
---|---|
Amitriptyline |
|
Venlafaxine (Effexor XR®) |
|
Atenolol (Tenormin®) |
|
Nadolol (Corgard®) |
|
- Children and adolescents
- The AAN published recommendations on preventive migraine therapy in children in 2019. The guidelines state that the efficacy of current therapies is suspect because in trials, up to 61% of children who received placebo reported ≥ 50% reduction in headache frequency. In almost all trials, medications were not superior to placebo. Topiramate is the only FDA-approved medication for migraine prevention in children, and it is approved for children aged 12 - 17 years.
- Given the lack of proven efficacy, the guidelines recommend that providers discuss treatment options with patients and family, but they do not recommend one medication over another. The table below lists some common medications that have been studied in pediatric migraine prevention trials. The AAN guidelines do not give specific criteria for starting preventive therapy, but criteria that are generally used in trials include ≥ 4 headache days a month and/or 3 - 4 migraine attacks per month for at least 3 months.
Medications for preventing migraines in children and adolescents | |
---|---|
Medication | Dosing and study |
Valproic acid (Depakote®) |
|
Topiramate (Topamax®) |
≥ 12 years old
|
Amitriptyline |
|
Cyproheptadine |
|
Propranolol |
|
- Menstrual migraine
- Menstrual migraines are migraines that are related to menstruation. They typically occur within 5 days (-2 to +3) of the onset of menses.
- Several triptans have been shown to be effective in preventing menstrual migraine when taken daily for short periods around the onset of menses
Medications for preventing menstrual migraine | |
---|---|
Medication | Dosing and study |
Frovatriptan (Frova®) |
|
Naratriptan (Amerge®) |
|
Zolmitriptan (Zomig®) |
|
- Pregnancy and nursing
- In general, 60 - 70% of women see an improvement in their migraine headache symptoms during pregnancy. Up to 20% see their migraines disappear. [12]
- Medications that have been used in pregnancy and nursing are presented in the tables below
Preventive therapies in pregnancy | |
---|---|
Propranolol Metoprolol |
|
Amitriptyline |
|
Aspirin |
|
Preventive therapies in nursing | |
---|---|
Propranolol |
|
Metoprolol |
|
Amitriptyline |
|
Aspirin |
|
- STUDIES | ACUTE TREATMENT
- The trial enrolled 3005 patients with > 1 year history of disabling migraine with or without aura
Main inclusion criteria
- ≥ 1 year history of disabling migraine
- Meet IHS diagnostic criteria
- MIDAS score ≥ 11
- Onset before age 50 years
- 3 - 8 migraines a month
Main exclusion criteria
- ≥ 15 headache days/month
- Epilepsy
- Vestibular migraine
- Diabetes with complications
- ≥ 3 doses/month of opiate or barbiturate
Baseline characteristics
- Average age 43 years
- Female sex - 84%
- Average migraines/month - 5.3
- Average years with migraines - 18
- Migraine with aura - 36%
- MBS: Photophobia - 50% | Phonophobia - 21% | Nausea - 21%
Randomized treatment groups
- Group 1 (528 patients): Lasmiditan 200 mg
- Group 2 (532 patients): Lasmiditan 100 mg
- Group 3 (556 patients): Lasmiditan 50 mg
- Group 4 (540 patients): Placebo
- Patients were instructed to take their assigned medication within 4 hours of next migraine attack
- The study had another arm that looked at a second dose of study drug in patients who did not respond to the first dose. Results from that arm were not reported in this publication.
- Of the 3005 enrolled patients, only 2156 patients treated a headache within 4 hours of onset and were included in the final analysis
Primary outcomes: Proportion of patients who were headache pain-free and most bothersome symptom (MBS) free at 2 hours after the first dose
Results
Duration: 72 hours | |||||
Outcome | Las 200 mg | Las 100 mg | Las 50 mg | Placebo | Comparisons |
---|---|---|---|---|---|
Headache pain-free | 38.8% | 31.4% | 28.6% | 21.3% | 1 and 2 vs 4 p <0.001 | 3 vs 4 p=0.003 |
MBS-free | 48.7% | 44.2% | 40.8% | 33.5% | 1 and 2 vs 4 p <0.001 | 3 vs 4 p=0.009 |
Dizziness | 18% | 18.1% | 8.6% | 2.5% | N/A |
Somnolence | 6.5% | 4.6% | 5.4% | 2.0% | N/A |
Paresthesia | 6.6% | 5.8% | 2.4% | 0.9% | N/A |
Findings: Lasmiditan was effective at 2 h post-dose for acute treatment of migraine at all oral doses tested. Efficacy and safety were consistent with the previous phase 3 study.
- The study enrolled 1466 patients with ≥ 1-year history of migraine headache with or without aura
Main inclusion criteria
- ≥ 1-year history of migraine
- Meet IHS diagnostic criteria
- Migraine onset before age 50 years
- 2 - 8 severe migraines/month
- < 15 headache days/month
Main exclusion criteria
- Alcohol or drug abuse
Baseline characteristics
- Average age 40 years
- Female sex - 85%
- Migraine with aura - 30%
- Average # of moderate-severe attacks/month - 4.6
- MBS: Photophobia - 57% | Nausea - 23% | Phonophobia - 19%
Randomized treatment groups
- Group 1 (669 patients): Rimegepant 75 mg one time with moderate-severe migraine headache
- Group 2 (682 patients): Placebo
- Subjects were allowed to take other rescue medications (e.g. NSAIDs, antinausea) if necessary 2 hours post-dose
Primary outcomes: Freedom from pain and freedom from the most bothersome symptom (MBS) associated with migraine at 2 hours post-dose
Results
Duration: 48 hours | |||
Outcome | Rimegepant | Placebo | Comparisons |
---|---|---|---|
Freedom from pain | 21% | 11% | p<0.0001 |
Freedom from MBS | 35% | 27% | p=0.0009 |
Nausea | 2% | <1% | N/A |
|
Findings: In the acute treatment of migraine, a single 75 mg dose of rimegepant in an orally disintegrating tablet
formulation was more effective than placebo. Tolerability was similar to placebo, with no safety concerns.
- The trial enrolled 1667 patients with ≥ 1-year history of migraine headache with or without aura
Main inclusion criteria
- ≥ 1-year history of migraine
- Meet IHS diagnostic criteria
- Migraine onset before age 50 years
- 2 - 8 moderate-severe migraines/month
Main exclusion criteria
- ≥ 15 headache days/month
- Previous CGRP-based treatment
- Significant CVD
- Significant liver disease
Baseline characteristics
- Average age 41 years
- Female sex - 88%
- Use of preventive med - 23%
- MBS: Photophobia - 56% | Phonophobia - 22% | Nausea - 21%
Randomized treatment groups
- Group 1 (456 patients): Placebo
- Group 2 (423 patients): Ubrogepant 50 mg with moderate-severe migraine headache
- Group 2 (448 patients): Ubrogepant 100 mg with moderate-severe migraine headache
- The study had another arm that looked at a second dose of study drug in patients who did not respond to the first dose. Results from that arm were not reported in this publication.
- Of the 1667 enrolled patients, only 1327 patients correctly followed the protocol and were included in the final analysis
Primary outcomes: Freedom
from pain at 2 hours after the initial dose of
ubrogepant or placebo and absence of the most
bothersome symptom (MBS) associated with migraine
at 2 hours
Results
Duration: 24 hours | ||||
Outcome | Placebo | Ubr 50 mg | Ubr 100 mg | Comparisons |
---|---|---|---|---|
Pain-free at 2 hours | 11.8% | 19.2% | 21.2% | 2 vs 1 p=0.002 | 3 vs 1 p<0.001 |
MBS-free at 2 hours | 27.8% | 38.6% | 37.7% | 2 or 3 vs 1 p=0.002 |
Pain relief at 2 hours | 49.1% | 60.7% | 61.4% | 2 or 3 vs 1 p=0.002 |
Nausea | 1.6% | 1.7% | 4.1% | N/A |
Somnolence | 0.8% | 0.6% | 2.5% | N/A |
Dry mouth | 0.4% | 0.6% | 2.1% | N/A |
Findings: A higher percentage of participants who received ubrogepant than of those who received placebo had freedom from pain and absence of the most bothersome symptom
at 2 hours after the dose. The most commonly reported adverse events were nausea,
somnolence, and dry mouth. Further trials are needed to determine the durability and
safety of ubrogepant for acute migraine treatment and to compare it with other drugs
for migraine.
- STUDIES | PREVENTIVE
- The trial enrolled children 8 to 17 years old with ≥ 4 migraines/month
Main inclusion criteria
- Females or males 8 - 17 years
- Migraine with or without aura or chronic migraine
- ≥ 4 migraine days a month
Main exclusion criteria
- Current use of preventive migraine med
- Previously failed amitriptyline or topiramate
- Prolonged QT interval (≥ 450 msec)
Baseline characteristics
- Average age - 14 years
- Average # of headache days/month - 11
- Female sex - 69%
Randomized treatment groups
- Group 1 (144 patients): Amitriptyline target dose of 1 mg/kg/day given in 2 divided doses
- Group 2 (145 patients): Topiramate target dose of 2 mg/kg/day given in 2 divided doses
- Group 3 (72 patients): Placebo
- Doses were increased every 2 weeks over 8 weeks
- The trial had a 28-day baseline period before randomization
Primary outcome: Relative reduction of 50% or more in the number of headache days in the comparison of the 28-day baseline period with the last 28 days of a
24-week trial
Results
Duration: 24 weeks | ||||
Outcome | Amitriptyline | Topiramate | Placebo | Comparisons |
---|---|---|---|---|
Primary outcome | 52% | 55% | 61% | 1 vs 3: p=0.26 | 2 vs 3: p=0.48 |
Reduction in headache days/month | 6.7 | 6.7 | 5.9 | 1 vs 3: p=0.36 | 2 vs 3: p=0.41 |
Findings: There were no significant differences in reduction in headache frequency or headache-related disability in childhood and adolescent migraine with amitriptyline,
topiramate, or placebo over a period of 24 weeks. The active drugs were associated with higher rates of adverse events.
- The trial enrolled 955 patients with episodic migraine headache
Main inclusion criteria
- History of migraine with or without aura for at least 12 months before screening
- 4 - 15 migraine days per month
Main exclusion criteria
- Older than 50 years of age at migraine onset
- History of hemiplegic migraine or cluster headache
- Prior nonresponse to more than two migraine-preventive treatment categories
- Taking ≥ 2 migraine preventive medications
Baseline characteristics
- Average age - 41 years
- Female sex - 85%
- Taking preventive migraine medication at baseline - 3%
- Average migraine days per month - 8.3
- Failed previous preventive treatment - 40%
Randomized treatment groups
- Group 1 (316 patients) - Placebo injection
- Group 2 (312 patients) - Erenumab 70 mg SQ once monthly
- Group 3 (318 patients) - Erenumab 140 mg SQ once monthly
- Abortive medications including triptans and ergotamines were allowed for acute treatment
- The trial had a 4-week run-in phase before patients were randomized to the 6-month double-blind treatment phase
Primary outcome: Change in mean number of migraine days per month from baseline to the final 3 months (months 4 through 6) of the double-blind treatment phase
Results
Duration: 6 months | ||||
Outcome | Placebo | Ere 70 | Ere 140 | Comparisons |
---|---|---|---|---|
Primary outcome | -1.8 | -3.2 | -3.7 | Group 2 or 3 vs 1 p<0.001 |
Reduction of ≥ 50% in migraine days/month | 27% | 43% | 50% | Group 2 or 3 vs 1 p<0.001 |
Change in days/month using acute migraine meds | -0.2 | -1.1 | -1.6 | Group 2 or 3 vs 1 p<0.001 |
|
Findings: Erenumab administered subcutaneously at a monthly dose of 70 mg or 140 mg significantly reduced migraine frequency, the effects of migraines on
daily activities, and the use of acute migraine-specific medication over a period of 6 months. The long-term safety and durability of the effect of erenumab require further study.
- The trial enrolled 246 patients with episodic migraine who had failed previous treatment
Main inclusion criteria
- History of episodic migraine with or without aura for at least 12 months
- Failed previous treatment (in terms of either efficacy or tolerability, or both) with 2 - 4 migraine preventive therapies. Preventive therapies included propranolol, metoprolol, topiramate, flunarizine, valproate, amitriptyline, venlafaxine, lisinopril, candesartan, or other locally approved preventives.
Main exclusion criteria
- Older than 50 years at migraine onset
- Active chronic pain syndrome
Baseline characteristics
- Average age - 44 years
- Female - 80%
- Average monthly migraine days - 9.2
- Previous unsuccessful treatments: Topiramate - 85%, Propranolol - 45%, Amitriptyline - 45%, Metoprolol - 38%, Valproate - 28%
Randomized treatment groups
- Group 1 (121 patients): Erenumab 140 mg SQ once monthly
- Group 2 (125 patients): Placebo
Primary outcome: Proportion of patients who achieved at least a 50% reduction from their individual baseline in the number of monthly migraine
days during the third month of the double-blind treatment phase (ie, weeks 9–12)
Results
Duration: 12 weeks | |||
Outcome | Erenumab | Placebo | Comparisons |
---|---|---|---|
Primary outcome (≥ 50% reduction) | 30% | 14% | OR 2.7 95%CI [1.4 - 5.2], p=0.002 |
Primary outcome (≥ 75% reduction) | 12% | 4% | OR 3.2 95%CI [1.1 - 9.0], p=0.025 |
Primary outcome (100% reduction) | 6% | 0% | N/A |
Reduction in monthly migraine days (weeks 9 - 12) | 1.8 days | 0.2 days | Diff 1.6 95%CI [0.5 - 2.7], p=0.004 |
|
Findings: Compared with placebo, erenumab was efficacious in patients with episodic migraine who previously did not respond to or tolerate between two and
four previous migraine preventive treatments. Erenumab might be an option for patients with difficult-to-treat migraine who have high unmet needs and few treatment options.
- The trial enrolled 1130 patients with episodic migraine
Main inclusion criteria
- Age 18 to 70 years with migraine onset at ≤ 50 years of age
- History of migraine for ≥ 12 months prior to screening
- Headache occurring on ≥ 15 days each month
- Using ≤ 1 preventive medication
Main exclusion criteria
- Patients using opioids or barbiturates
- Taking preventive treatment and previously failed ≥ 2 previous preventive treatments
- Unremitting headaches (headaches for > 80% of awake time)
Baseline characteristics
- Average age - 41 years
- Female - 87%
- Average monthly headache days - 13
- Taking preventive medication - 21%
- Previous use of topiramate - 30%
Randomized treatment groups
- Group 1 (376 patients): Fremanezumab 675 mg once every 3 months
- Group 2 (379 patients): Fremanezumab 675 mg one time followed by 225 mg at weeks 4 and 8
- Group 3 (375 patients): Placebo
Primary outcome: Mean change from baseline in the average number of headache days (defined as days in which headache pain lasted ≥4 consecutive hours and had a peak severity of at least a moderate level or days in which acute
migraine–specific medication [triptans or ergots] was used to treat a headache of any severity or duration) per month during the 12 weeks after the first dose
Results
Duration: 12 weeks | ||||
Outcome | Frem every 3 mon | Frem monthly | Placebo | Comparisons |
---|---|---|---|---|
Primary outcome | -4.3 | -4.6 | -2.5 | 1 or 2 vs 3 p<0.001 |
Change in days/month using acute migraine meds | -3.7 | -4.2 | -1.9 | 1 or 2 vs 3 p<0.001 |
≥ 50% reduction in mean HA days/month | 38% | 41% | 18% | N/A |
|
Findings: Fremanezumab as a preventive treatment for chronic migraine resulted in a lower frequency of headache than placebo in this 12-week trial. Injection-site reactions
to the drug were common. The long-term durability and safety of fremanezumab require further study.
- The FOCUS trial enrolled 838 patients with episodic (6 - 14 headaches/month) or chronic migraines (≥ 15 headaches/month) who had failed 2 - 4 preventive therapies
Main inclusion criteria
- Migraine diagnosis before age of 50 years
- Migraines for ≥ 12 months prior
- Episodic or chronic migraines with or without aura
- Failure of 2 - 4 preventive meds in last 10 years
Main exclusion criteria
- Current use of preventive med
- Previous CGRP use
- Significant cardiovascular disease
Baseline characteristics
- Average age 46 years
- Female - 84%
- Episodic migraine - 40% | Chronic migraine - 60%
- Average years since diagnosis - 24
- Average migraine days/month - 14
- Average days of acute headache med/month - 12.6
- Number of failed meds: 2 - 50% | 3 - 32% | 4 - 18%
Randomized treatment groups
- Group 1 (276 patients): Fremanezumab 675 mg SQ one time followed by monthly placebo
- Group 2 (283 patients): Fremanezumab 225 mg (episodic) or 675 mg (chronic) SQ one time followed by 225 mg every month
- Group 3 (279 patients): Placebo
- Anticonvulsants (70%), beta blockers (56%), and tricyclic antidepressants (46%) were the most common classes of migraine preventive medications that patients had failed previously
- There was a 28-day run-in period before randomization where participants recorded their headache frequency
- Acute migraine treatments were continued as needed
Primary outcome: Mean change
from baseline (28-day run-in period) in the monthly
average number of migraine days during the entire
12 weeks after the first dose of study drug. A
migraine day was defined as a calendar day with ≥ 4 consecutive hours of a migraine with or without
aura as per ICHD-3 diagnostic criteria, or a headache
of any duration treated with migraine-specific acute
medications (triptans or ergot compounds).
Results
Duration: 12 weeks | ||||
Outcome | Frem once | Frem monthly | Placebo | Comparisons |
---|---|---|---|---|
Primary outcome | -3.7 | -4.1 | -0.6 | 1 or 2 vs 3 p<0.0001 |
≥ 50% reduction in monthly migraine days | 34% | 34% | 9% | 1 or 2 vs 3 p<0.0001 |
% change in days/month with headache | -34.9% | -36.8% | -8.5% | N/A |
|
Findings: Fremanezumab was effective and well tolerated in patients with difficult-to-treat migraine who had
previously not responded to up to four classes of migraine preventive medications
- The trial enrolled 1591 adults with at least a 1-year history of migraine headache
Main inclusion criteria
- Age ≥ 18 years
- ≥ 1-year history of migraine with aura, migraine without aura, or chronic migraine
- 4 - 18 moderate-to-severe migraines per month
- Age of onset < 50 years
Main exclusion criteria
- History of nonresponse to > 2 preventive drug categories
- Alcohol or drug abuse
- Basilar migraine or hemiplegic migraine
- Chronic pain syndrome (e.g. fibromyalgia)
Baseline characteristics
- Average age 41 years
- Female sex - 83%
- Average migraine days/month - 10.1
- Migraine with aura - 40%
- Average age of migraine onset - 18 years
Randomized treatment groups
- Group 1 (370 patients): Rimegepant 75 mg every other day
- Group 2 (371 patients): Placebo
- The study had a 4-week run-in observation period where all subjects documented their daily migraines and treatments used
- Participants were allowed to take one preventive migraine drug, excluding CGRP receptor antagonists and CGRP monoclonal antibodies, provided that the dose was stable for at least 3 months before the 4-week observation period and did not change during the observation period or the double-blind treatment phase
- Rescue medications that were permitted during the trial included triptans, NSAIDs, paracetamol, aspirin, caffeine, baclofen, antiemetics, and muscle relaxants
Primary outcome: Change from the 4-week observation period in the mean number of migraine days per month in the last 4 weeks of the double-blind treatment phase (weeks 9–12)
Results
Duration: 12 weeks | |||
Outcome | Rimegepant | Placebo | Comparisons |
---|---|---|---|
Primary outcome | -4.3 | -3.5 | p=0.0099 |
> 50% reduction in migraine days | 49% | 41% | p=0.044 |
Rescue medication days | 3.7 | 4 | p=0.39 |
|
Findings: Taken every other day, rimegepant was effective for preventive treatment of migraine. Tolerability was
similar to that of placebo, and no unexpected or serious safety issues were noted.
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