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Qulipta for Migraine 2024

The medical problem migraine has a number of associated problems.  Persons with migraine, called migraineurs, have motion sickness which may bother them while travelling in boats or cars, especially the back seat of a car.  Migraineurs usually have significant photophobia, or sensitivity to light, causing them to wear hats with brims and sunglasses.

To learn the subject read my article “What is Migraine?” on my website, www.doctormigraine.com. Click here to read.

Migraine attacks can be very disabling and are a common cause of missing work or school.  Migraine attacks run up medical bills for doctor visits, MRI scans, and medication.

Migraine is a great problem, but in the last few years the discovery of medications which block the effect of the inflammatory chemical, CGRP, has been a great discovery.

Developed by biopharmaceutical company AbbVie, Qulipta (atogepant) is an oral, small molecule, calcitonin gene-related peptide (CGRP) receptor antagonist.

Qulipta is another one of the powerful new drugs, which works well with other medications and has few side effects.  All the available CGRP blockers have been delivered either by subcutaneous or intravenous injection.  It would be nice to have an oral drug, which is a CGRB receptor inhibitor. That drug is Qulipta.

Read my eBook on Migraine-click here.

This is an article by Britt Talley Daniel MD, retired member of the American Academy of Neurology, migraine textbook author, podcaster, YouTube video producer, and blogger.

Qulipta is FDA approved for adults with episodic and chronic migraine.  Qulipta reduces the frequency of migraine attacks per month by more than half.   It is a CGRP receptor antagonist, acting within the migraine process to decrease attacks.

Episodic migraine is defined by the International Classification of Headache Disorders, ICHD v 3, as less than fourteen migraine headaches per month. Chronic migraine is defined as fifteen or more headaches per month with at least eight fulfilling the criteria for migraine for three months.

What kind of drug is Qulipta?

Qulipta is called a “Gepant,” which is a small molecule, calcitonin gene-related peptide receptor antagonist. Other similar gepants are Ubrelvy (ubrogepant) and Nurtec (rimegepant).  These medications block CGRP, a protein that is released in the brain during a migraine attack.

Qulipta acts on the CGRP protein during the Migraine Timing Cycle.

It is generally thought that local vasodilatation of intracranial extracerebral blood vessels and a consequent stimulation of surrounding trigeminal sensory nervous pain pathways is a key mechanism underlying the generation of headache pain associated with migraine.

This activation of the 'trigeminovascular system' is thought to cause the release of vasoactive sensory neuropeptides, especially CGRP, that increase the pain response. The activated trigeminal nerves convey nociceptive information to central neurons in the brain stem trigeminal sensory nuclei that in turn relay the pain signals to higher centers where headache pain is perceived.

It has been hypothesized that these central neurons may become sensitized as a migraine attack progresses. Many of the new migraine acute and preventive therapy drugs act to block the effect of CGRP.

The Migraine timing cycle has four stages which are:

1 Trigeminal activation and cerebral arterial vasodilation.

2 Twenty to forty minutes later the neurochemicals CGRP, Neurokinin A, and Substance P are released by the migraine process from ganglia, and they inflame the trigeminal nerve, the arteries, and later the thalamus.

3 At two hours the cerebral arteries vasodilate and are inflamed.  Blood pulsing through dilated, inflamed arteries causes pulsatile, pounding headache.

4 Past three hours the thalamus, also known as the pain center of the brain, is turned on by the migraine process.

If I drop a brick on my foot the tissue of the foot is damaged and the pain is carried by pain nerves in the foot to the leg, to the spinal cord, and up to the thalamus in the brain where pain is registered.

Migraine is a chemical inflammatory condition affecting the 5th, trigeminal, nerve, the arteries, and the thalamus.  Phase 4 is also called central sensitization, and this is the worst and most painful part of a migraine.  During central sensitization touch may be perceived as painful, so the head is sensitive to touch or wear glasses or lie on one side in the bed.

This is called allodynia, a sure clinical sign of central sensitization.  Central sensitization is like sunburn.  Normally it doesn’t hurt to touch my arm, but if it does if it is sunburned.  Sunburn is like allodynia.

The Migraine Timing Cycle

Read my article “How to treat Migraine Headaches” on my website, www.doctormigraine.com. Please click here to read.

What are the other new drugs like Qulipta that act on migraine by blocking CGRP?

There are three drugs released for prevention by subcutaneous injection once a month- Aimovig (erezumab), Ajovy (fremanezumab), and Emgality (galcanezumab). Vyepti (eptinezumbab) is given by intravenous injection monthly for migraine prevention.

Nurtec (rimegepant) is an oral gepant for migraine prevention.

Three oral gepants have been released for acute migraine treatment and they are Nurtec (rimegepant), Ubrelvy (ubrogepant), and Qulipta (atogepant).

What are common side effects of Qulipta?

The drug has no black-box warning and is tolerated well with the most common side effects being:

Constipation (6.9% to 7.7% of participants across all dosages)

Nausea (4.4 to 6.1% across all dosages)

Upper respiratory tract infection (3.9% to 5.7% across all dosages)

Qulipta has been associated with weight loss for many patients and the reason for this is not understood.

What is important safety information regarding Qulipta?

Persons taking Qulipta should discuss with their healthcare provider:

If they have kidney failure or need for dialysis.

If they have liver failure.

If they plan pregnancy or breastfeeding since Qulipta is not indicated for either condition.

What was the efficacy of Qulipta?

In an investigative study nine hundred patients reported four to fourteen migraine days per month with a mean of slightly less than eight migraine days per month.

Size of dose didn’t make much difference as noted by the table below:

3.7 migraine days per month for the 10 mg group

3.9 migraine days per month for the 30 mg group

4.2 migraine days per month for the 60 mg group

2.5 migraine days per month for the placebo group

Does Qulipta work for Chronic Migraine Patients?

As of April of 2023 Qulipta is approved by the FDA for migraine prevention and use with chronic migraine patients. The dose for migraine prevention is given twice a day and patients experience more constipation as a side effect at the increased dose. 

Interesting comments about Qulipta by migraine experts.

“It is exciting to see CGRP-targeted therapies mature,” says Richard B. Lipton, MD, Albert Einstein College of Medicine.  “We have known for many years that CGRP plays a crucial role in the biology of migraine, thanks to the pioneering work of Lars Edvinsson and Peter Goadsby. Now we have five agents approved for the preventive treatment of migraine that specifically target CGRP.  I look forward to adding atogepant to this robust CGRP-targeted preventive armamentarium. These new options are highly effective, have a rapid onset of action, and excellent tolerability.”

“CGRP is one of the greatest translational science stories in medicine,” says Dr. Lipton. “We have gone from laboratory findings that show CGRP is important in vasodilation and pain, to human studies that show its role in migraine, to the development of a robust set of novel treatments.

“Since 1 billion people globally have migraine, including 40 million in the United States, this is great news for a huge number of people. That includes those with migraine, their families, and employers — and for clinicians who treat them — with wonderful new tools for reducing the burden of the world’s second most disabling disorder.”

“Overall, this study showed us that atogepant was safe and, surprisingly, seems pretty effective regardless of the dose,” says lead study author Jessica Ailani, MD, director of MedStar Georgetown Headache Center and associate professor of neurology at Georgetown University.

"There is a difference between daily vs. every other day dosing that might change the efficacy and also the side-effect profile," says Dr. Ailani. "This may help patients decide which gepant preventive is right for them since both are on the market at the same time."

“Roughly 40% of patients living with migraine should be on preventive medication or other treatment, but probably fewer than 15% of patients with migraine are currently receiving therapy.” Alan Rapoport.

Read my big book on migraine here.

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 All the best.

 Britt Talley Daniel MD