THE LATEST MEDICATIONS FOR TREATING AND PREVENTING BREAKTHROUGH MIGRAINES

In some people, a migraine attack can be so severe that it prevents the person from performing day-to-day tasks and functioning normally, sometimes for days.

Despite taking the medications, many people do not respond to treatment and cannot prevent migraine attacks or relieve their symptoms once they start.

At the 2022 American Headache Society (AHS) Annual Scientific Meeting, researchers presented their latest findings regarding breakthrough migraine management.

They showed that combining Ubrogepant (a CGRP-receptor antagonist) and onabotulinumtoxinA can treat breakthrough migraines, and Eptinezumab can prevent migraines in patients who did not respond to other treatments.

Keep reading to learn more about breakthrough migraines and the new medications that can help treat and possibly prevent them. 

What Is A Breakthrough Migraine?

A breakthrough migraine is a migraine that does not respond to preventive treatment – people still get migraine attacks despite taking migraine medications.

A moderate to severe headache, migraines cause throbbing or pulsating pain, usually on one side of the head. 

People often experience other accompanying symptoms, such as nausea, vomiting, and increased sensitivity to lights and sounds.

Migraines can last for hours or even days, and the pain can be so severe it becomes debilitating.  

Migraine attacks can happen over several stages, including:

• Prodrome (pre-headache): People may feel sick or moody a day or two before the headache starts.
• Aura: Some people experience warning symptoms, known as an Aura, before or with a migraine headache. An Aura may include seeing flashes of flight, bright (blind) spots, and other visual disturbances that can distort sight for a few minutes or even an hour. Other symptoms, such as tingling on one side of the face, arm, or leg, and difficulty speaking can also occur.
• The migraine: The headache begins and can involve throbbing pain, nausea, and extreme sensitivity to light and sound.
• Postdrome: A “headache hangover” is when people feel tired and drained for a day or more after the migraine attack passes.

Some people do not experience symptoms before the headache starts, while others experience a “silent migraine” – an aura or other migraine symptoms without the headache.  

What causes migraine is still unknown. Scientists believe that migraines may happen due to changes in the brain stem and imbalances of brain chemicals, like serotonin and the calcitonin gene-related peptide (CGRP). 

When CGRP binds to its receptors in the brain (CGRP Receptors), it causes the blood vessels in the brain to dilate (widen) and become inflamed. Scientists suspect that can be a possible cause of migraines.

How To Treat Migraines?

There is no cure for migraines, especially since researchers still do not fully understand how the condition develops. However, many medications are available to fight migraines.

Migraine treatments aim to relieve symptoms and prevent future attacks. Your treatment will depend on how often you get migraines, the severity of your symptoms, and other medical conditions you may have.  

Medications that treat migraine can be pain-relieving medications or preventive medications.

Pain-relieving medications for migraine

Medications that relieve migraine pain are most effective when taken as soon as the first sign or symptom of a migraine begins.

These medications include the following:

• Pain killers: Over-the-counter pain meds, like paracetamol and ibuprofen, and prescription pain relievers can reduce migraine headaches.
• Triptans: Triptans are prescription drugs that block pain pathways in the brain and reverse the changes that can cause a migraine. These medications include sumatriptan (Imitrex, Tosymra) and rizatriptan (Maxalt, Maxalt-MLT).  
• Antiemetics: Anti-nausea drugs, like chlorpromazine, metoclopramide (Reglan), or prochlorperazine (Compro), can relieve feelings of nausea or sickness during a migraine attack.
• CGRP receptor antagonists: Ubrogepant (Ubrelvy) and Rimegepant (Nurtec ODT) are oral calcitonin gene-related peptide (CGRP) receptor antagonists – they block CGRP from binding to its receptors in the brain. They became approved for acute migraine treatment in adults (with or without aura). Drug studies revealed that two hours after taking these medications, they helped lessen pain and other migraine symptoms, such as nausea and light/sound sensitivity.
• Opioids: Narcotic opioids may help relieve the symptoms of people who cannot take other migraine meds. However, these drugs can be highly addictive.

Preventive medications for migraine

If your migraines are severe and frequent, your healthcare provider might prescribe medications that could prevent future migraine attacks.

Preventive migraine medications include the following:

• Meds that lower blood pressure: Blood pressure-lowering drugs can help prevent migraines with aura. These include beta-blockers (propranolol and metoprolol tartrate) and calcium channel blockers (verapamil). 
• Anti-seizure medications: Anti-seizure drugs like Valproate and topiramate might help with less frequent migraines. However, these meds can cause side effects, such as dizziness, weight changes, nausea, and more. 
• Antidepressants: Antidepressants, like the tricyclic antidepressant amitriptyline, can prevent migraines.
• CGRP monoclonal antibodies: Newer CGRP monoclonal antibody drugs became approved by the Food and Drug Administration to treat migraines. They include Erenumab-aooe (Aimovig), Fremanezumab-vfrm (Ajovy), Galcanezumab-gnlm (Emgality), and Eptinezumab-jjmr (Vyepti), administered as injections.
• Botox injections: OnabotulinumtoxinA (Botox) injections around every 12 weeks help prevent migraines in some people.

Migraines may persist despite the mentioned preventive treatments. Those are known as breakthrough migraines.  

What Is The Latest Breakthrough Migraine Medication?

Scientists found a new effective treatment combination for breakthrough migraines and a medication that can prevent chronic migraines that did not respond to previous treatments.

They presented their findings at the 2022 American Headache Society (AHS) Annual Scientific Meeting, held from June 9-12 in Denver, Colorado, and virtually.

The latest acute treatment for breakthrough migraines

Recently, researchers found that a combination of CGRP antagonists and onabotulinumtoxinA injections can be an effective medication for people with breakthrough migraines who did not respond to other treatments.

The scientists conducted a real-world, prospective, observational trial (the COURAGE study) to investigate the safety and efficacy of combining the CGRP antagonist Ubrogepant (Ubrelvy; AbbVie) with onabotulinumtoxinA to treat breakthrough migraines.

The trial included 122 participants taking onabotulinumtoxinA as migraine preventive treatment.

All participants had frequent breakthrough migraines (3 or more migraine attacks in the last 30 days despite preventive treatment) and used Ubrogepant (50 mg or 100 mg) to treat three or more breakthrough migraine attacks.

Patients had, on average, nine breakthrough migraine attacks during the 30 days and used Ubrogepant as acute treatment in combination with onabotulinumtoxinA (without an anti-CGRP mAb).

After receiving an Ubrogepant dose, the researchers collected assessments of the following:

• Whether patients had (MPR) meaningful pain relief (the pain was significantly reduced)
• Whether the patients could return to normal function (RNF) after taking the medication

They collected the data via the Migraine Buddy app.

The authors presented their evidence at the 2022 American Headache Society (AHS) Annual Scientific Meeting.

During the first breakthrough migraine attack:

• 53.3% of patients achieved meaningful pain relief (MPR) 2 hours after receiving a Ubrogepant dose
• 76.2% of patients achieved meaningful pain relief (MPR) 4 hours after receiving a Ubrogepant dose
• 25.4% of patients could return to normal function (RNF) 2 hours after receiving a Ubrogepant dose
• 45.9% of patients could return to normal function (RNF) 4 hours after receiving a Ubrogepant dose

Over the first ten breakthrough migraine attacks:

• 44.8% of patients achieved meaningful pain relief (MPR) 2 hours after receiving a Ubrogepant dose
• 72.9% of patients achieved meaningful pain relief (MPR) 4 hours after receiving a Ubrogepant dose
• 30.1% of patients could return to normal function (RNF) 2 hours after receiving a Ubrogepant dose
• 52.1% of patients could return to normal function (RNF) 4 hours after receiving a Ubrogepant dose

These findings support the real-world effectiveness of using Ubrogepant as an acute treatment for breakthrough migraines in combination with onabotulinumtoxinA.

The latest medication for preventing migraines in patients with prior treatment failures

Researchers also presented their findings on Eptinezumab, a medication that could prevent migraines in patients with episodic or chronic migraine and who had 2 to 4 prior treatment failures. 

The scientists conducted a phase 3b, double-blind, randomized clinical trial (the DELIVER study) to investigate the safety and efficacy of Eptinezumab (100 mg and 300 mg) for migraine prevention.

The study included 891 participants with episodic or chronic migraine who had 2 to 4 preventative treatment failures in the past ten years.

The patients received at least one intravenous (IV) dose of Eptinezumab 100 mg, Eptinezumab 300 mg, or a placebo every 12 weeks. 

The researchers assessed how many migraine days each patient experienced a month (monthly migraine days (MMD)) at the beginning of the trial compared to 12 weeks after receiving a dose.  

The authors found the following results:

• At 12 weeks, Eptinezumab (100 mg) significantly reduced the number of migraine days (patients experienced, on average, 4.8 fewer migraine days per month) compared to the placebo.
• At 12 weeks, Eptinezumab (300 mg) significantly reduced the number of migraine days (patients experienced, on average, 5.3 fewer migraine days per month) compared to the placebo.
• Over 1-12 weeks, 42.1% of patients treated with Eptinezumab 100 mg achieved ≥50% reduction in MMDs, and 15.7% achieved ≥75% reduction in MMDs.
• Over 1-12 weeks, 49.5% of patients treated with Eptinezumab 300 mg achieved ≥50% reduction in MMDs, and 18.8% achieved ≥75% reduction in MMDs.
• Between weeks 13-24, the patients still experienced fewer monthly migraine days (MMD decreased by 5.4 days in the Eptinezumab 100 mg group and by 6.1 days in the Eptinezumab 300 mg group on average) compared with the placebo.
• At week 12, Eptinezumab was associated with a significant decrease in the Headache Impact Test (HIT-6) compared to baseline among recipients who took 100 mg (mean difference, -6.9) and 300 mg (MD, -8.5) compared to those who took the placebo.

Patients who took Eptinezumab had similar side effects to those who took the placebo.

The authors concluded that eptinezumab significantly decreases the frequency of monthly migraine attacks compared to a placebo, and the drug was generally safe and well-tolerated in patients.

These two treatments are the latest in breakthrough migraine management. A combination of Ubrogepant and onabotulinumtoxinA can help treat breakthrough migraines, and Eptinezumab can help prevent migraines in people who did not respond to previous migraine treatments.

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Sources:

• Migraine Headache - StatPearls - NCBI Bookshelf
• New Approaches to Shifting the Migraine Treatment Paradigm - PMC 
• The Role of Calcitonin Gene-Related Peptide (CGRP) in Neurogenic Vasodilation and Its Cardioprotective Effects
• A Review of Eptinezumab Use in Migraine - PMC