Virtual Headache Specialist

GEPANTS (NURTEC, QULIPTA) VS. CGRP MONOCLONAL ANTIBODIES (AIMOVIG, AJOVY, EMGALITY, VYEPTI) FOR MIGRAINE PREVENTION. WHICH ARE BETTER?

gepants vs monoclonal antibodies for migraine prevention
Nurtec vs. Qulipta vs. Aimovig vs. Ajovy vs. Emgality vs. Vyepti for migraine prevention? Which is the best? It’s a complicated question, but the answer is actually quite simple as you’ll see…

The CGRP Monoclonal Antibodies for Migraine Prevention

The last few years have been monumental in strides for migraine treatment. New treatments for migraine were stagnant for decades until Aimovig (Erenumab), the first of 4 CGRP monoclonal antibodies (mAbs), became available in May 2018 for migraine prevention. Emgality (Galcanezumab), Ajovy (Fremanezumab), and Vyepti (Eptinezumab) were the other 3 CGRP mAbs that followed. The CGRP mAbs were the first medication ever designed purely for the prevention of migraine. All 4 of the CGRP mAbs are compared to each other in much greater detail here. There have been a number of migraine preventives used over the years, but none of them were made for the sole purpose of migraine prevention, but rather were found to be helpful for some people over time. These older historical migraine preventives included select medications within the antiseizure, antidepressant, and antihypertension medication classes.

The Gepants Entered the Scene as Migraine Abortives

In January 2020, the first of a new migraine abortive (“as needed”) class called the gepants came out with Ubrelvy (Ubrogepant), and Nurtec ODT (Rimegepant) followed the next month. Notably, another new abortive migraine class called the ditans also became available in January 2020 with Reyvow (Lasmiditan). The gepants and ditans were the first new classes of migraine abortive medication developed since the triptans in 1992. The gepants, triptans, and ditans are all compared to each other for migraine abortive treatment in much more detail here.

The Gepants for Migraine Prevention

Then, the gepants made a surprise pivot to include migraine preventive treatment to their repertoire in addition to abortive treatment. This began when Nurtec received dual FDA approval for migraine prevention in May 2021, in addition to its pre-existing FDA approval for migraine abortive treatment. So, it became the first and the only dually approved migraine abortive and preventive medication. Then in September 2021, the first gepant developed and studied purely for migraine prevention became available with Qulipta (Atogepant). Nurtec ODT and Qulipta are compared to each other for migraine prevention in much greater detail here.

How to Pick Between the Gepants and CGRP mAbs for Migraine Prevention

So now that we suddenly have a plethora of new preventive migraine treatments working on different targets in the CGRP migraine pathway between the CGRP mAbs and the gepants, how do you know which you should try, or which might work best for you? Here is what to ask yourself to help narrow down which to consider trying first for preventing migraine (not abortive/”as needed”). Do you prefer taking a pill, a once monthly self-injection (autoinjector by an easy push button), or a 30 minute quarterly (every 3 months) IV infusion? If you prefer a pill, the options are the gepants and include either Nurtec every other day or Qulipta once daily. If you prefer a once monthly self-injection, the options are the CGRP mAbs and include Aimovig, Emgality, and Ajovy. If you prefer a once quarterly 30-minute IV infusion, then the only option is the newest CGRP mAb called Vyepti.

Are the Gepants or the CGRP mAbs Better for Migraine Prevention?

So back to our original question. Which of all of these new migraine preventive options are the best? The short answer is that every one of these medications has been a huge step forward in migraine treatment, and there are no bad choices. They are all excellent choices. As you can see in the table below, we are seeing results such as 75% and 100% reduction in monthly migraines with many of these medications. These aren’t treatment results that we’ve been used to discussing with older preventive treatment options. Of course, those types of results are also not the goal nor should they ever be the expectation with any preventive treatment. However, it is fantastic to see these types of results can be possible for some patients (called “super responders”). In addition, everyone responds differently to medications in terms of benefits and side effects. So first, decide if you have a preference on the route of administration as mentioned above (pill, injection, infusion). That’s the best place to start, and you can always switch to another type if you’re not receiving benefit with one of them, or having side effects with one. The table below compares the data on migraine prevention between the gepants (Nurtec and Qulipta), and the CGRP mAbs (Aimovig, Emgality, Ajovy, Vyepti). Keep in mind, these data are not from head-to-head studies between each of the medications. The following data comes from that reported within each individual medication compared to placebo in their respective trials.
Nurtec ODT (Rimegepant) Qulipta (Atogepant) Aimovig (Erenumab) Ajovy (Fremanezumab) Emgality (Galcanezumab) Vyepti (Eptinezumab)
Medication Class Gepant Gepant CGRP monoclonal antibody CGRP monoclonal antibody CGRP monoclonal antibody CGRP monoclonal antibody
Mechanism of Action CGRP receptor antagonist CGRP receptor antagonist CGRP receptor antagonist CGRP ligand antagonist CGRP ligand antagonist CGRP ligand antagonist
Peak Serum Concentration 90 minutes 90 minutes 6 days 5-7 days 5 days 30 minutes (after infusion)
½ life 11 hours 11 hours 28 days 31 days 27 days 27 days
Available dosing 75 mg orally dissolvable tablet 10 mg, 30 mg, 60 mg pill 70 mg or 140 mg once monthly by subcutaneous autoinjector 225 mg once monthly or 675 mg once quarterly by autoinjector or syringe 240 mg subcutaneous autoinjector for 1stmonth followed by 120 mg monthly 100 mg or 300 mg quarterly by 30-minute intravenous (IV) infusion
Dosing frequency 1 pill every other day 1 pill daily One injection monthly One injection monthly or 3 injections quarterly One injection monthly One infusion quarterly
Reduction of monthly migraine days across weeks 1-12 Averaged weeks 9-12: 75 mg: -4.3 Placebo: -3.5 Averaged weeks 1-12: 75 mg: -3.6 Placebo: -2.7 Averaged weeks 9-12: 10 mg: -4.24 30 mg: -4.25 60 mg: -4.44 Placebo: -2.5 Averaged weeks 1-12: 10 mg: -3.7 30 mg: -3.9 60 mg: -4.2 Placebo: -2.5 N/A 675 mg quarterly: -3.7 225 mg monthly: -3.4 Placebo: -2.2 *Months 1-3 in long term extension study (open label): 675 mg quarterly: -4.7 225 mg monthly: -4.8 120 mg monthly: -4.1 Placebo: -2.1 100 mg: -3.9 300 mg: -4.3 Placebo: -3.2
% reduction of migraine days in week 1 75 mg: 30% Placebo: 9.4% 10 mg: N/A 30 mg: N/A 60 mg: 53% Placebo: 15% N/A N/A N/A N/A
% reduction of migraine days in weeks 1-12 N/A 10 mg: N/A 30 mg: N/A 60 mg: 54% Placebo: 33% N/A N/A N/A N/A
% of patients with a 50% or more decrease in monthly migraine days across weeks 1-12 75 mg: 49% Placebo: 41% *Assessed during weeks 9-12 only, not weeks 1-12 10 mg: 56% 30 mg: 59% 60 mg: 61% -Weeks 1-4: 61% -Weeks 5-8: 66% -Weeks 9-12: 71% Placebo: 29% 70 mg: 41.3% 140 mg: 48.1% Placebo: 26.3% 675 mg quarterly: 44.4% 225 mg monthly: 47.7% Placebo: 27.9% *At month 3 alone (not averaged over months 1-3): 675 mg quarterly: 49% 225 mg monthly: 51% Placebo: 37% *At month 3 in long term extension study (open label): 675 mg quarterly: 59% 225 mg monthly: 61% 120 mg: 55% Placebo: 32% *At month 2 alone: 120 mg: 54.1% Placebo: 34.5% *At month 3 alone: 120 mg: 57.7% Placebo: 37.9% 100 mg: 49.8% 300 mg: 56.3% Placebo: 37.4%
% of patients with a 75% or more decrease in monthly migraine days across weeks 1-12 N/A 10 mg: 30% 30 mg: 30% 60 mg: 38% -Weeks 1-4: 39% -Weeks 5-8: 41% -Weeks 9-12: 50%   Placebo: 11% N/A 675 mg quarterly: 18.4% 225 mg monthly: 18.5% Placebo: 9.7% *At month 3 alone (not averaged over months 1-3): 675 mg quarterly: 30% 225 mg monthly: 29% Placebo: 10% 120 mg: 30% Placebo: 14% *At month 2 alone: 120 mg: 31.2% Placebo: 11% *At month 3 alone: 120 mg: 34.2% Placebo: 12.8% 100 mg: 22.2% 300 mg: 29.7% Placebo: 16.2%
% of patients with a 100% decrease in monthly migraine days across weeks 1-12 N/A 10 mg: 8% 30 mg: 5% 60 mg: 8% -Weeks 1-4: 19% -Weeks 5-8: 24% -Weeks 9-12: 28% Placebo: 1% N/A 675 mg quarterly: 0.7% 225 mg monthly: 2.4% Placebo: 0% 120 mg: 11% Placebo: 4% *At month 2 alone: 120 mg: 11.8% Placebo: 3.7% *At month 3 alone: 120 mg: 12.2% Placebo: 7.3% 100 mg: 11.4% 300 mg: 16.8% Placebo: 9.1%
Side effects: Nasopharyngitis N/A N/A 70 mg: 3-9.9% 140 mg: 2-11% Placebo 6-10% 675 mg quarterly: 5-8% 225 mg monthly: <1-8% Placebo: 4-9% 120 mg: 7.4% Placebo: 6.5% 100 mg: 6% 300 mg: 8% Placebo: 6%
Side effects: Hypersensitivity reactions <1% <1% 70 mg: <1% 140 mg: <1% Placebo: <1% 675 mg quarterly: <1% 225 mg monthly: <1% Placebo: <1% 120 mg: 1% Placebo: 1% 100 mg: 1% 300 mg: 2% Placebo: 0%
Side effects: Constipation N/A Constipation 10 mg: 6% 30 mg: 6% 60 mg: 9% Placebo: 1% 70 mg: 1% 140 mg: 3% Placebo 1% 675 mg quarterly: <1% 225 mg monthly: <1% Placebo: <1% 120 mg: 1% Placebo: <1% 100 mg: <1% 300 mg: <1% Placebo: <1%
Side effects: Nausea 75 mg: 2.7% Placebo: 0.8% Nausea 10 mg: 5% 30 mg: 6% 60 mg: 9% Placebo: 3% N/A N/A N/A N/A
Side effects: Abdominal discomfort 75 mg: 2.4% Placebo: 0.8% N/A N/A N/A N/A N/A
Side effects: Cramps, muscle spasms N/A N/A 70 mg: <1% 140 mg: 2% Placebo <1% 675 mg quarterly: <1% 225 mg monthly: <1% Placebo: <1% 120 mg: <1% Placebo: <1% 100 mg: <1% 300 mg: <1% Placebo: <1%
Side effects: Injection site reactions N/A N/A 70 mg: 6% 140 mg: 5% Placebo 3% 675 mg quarterly: 18-19% 225 mg monthly: 23% Placebo: 4% 120 mg: 18% Placebo: 13% N/A
Side effects: Somnolence/ fatigue N/A 10 mg: 4% 30 mg: 4% 60 mg: 6% Placebo: 3% N/A N/A N/A N/A
Side effects: Decreased appetite   N/A 10 mg: 2% 30 mg: 1% 60 mg: 2% Placebo: <1% % of Patients with Weight Loss of 7% or More 10 mg: 3.8% 30 mg: 3.2% 60 mg: 4.9% Placebo: 2.8% N/A N/A N/A N/A
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FAQ

Gepants are the newest class of migraine medications used to treat migraines as they happen. They should be taken when the migraine pain starts. Some are also used to prevent migraines. Gepants work by blocking the CGRP receptor and preventing the CGRP protein released during a migraine from triggering the migraine headache. Gepants are available in pills, nasal spray (pending), and disintegrating tablets. Some can be taken daily or every other day throughout the month to help decrease the number of migraines that a person has. 

Some common types of gepants include: Ubrelvy, Nurtec, and Qulipta.

CGRP monoclonal antibodies are biological medications that are partly made from human proteins. They are used for migraine prevention. Monoclonal antibodies will bind and inactivate very specific inflammatory proteins that are already in your body which are normally involved in triggering a migraine attack. Some common types of monoclonal antibodies include: Aimovig, Ajovy, Emgality, and Vyepti.

CGRP is an abbreviation for calcitonin gene-related peptide. This is a very inflammatory protein that is released in the brain from the trigeminal nerves during a migraine. It’s a common source of inflammation that occurs during  migraine attacks. Gepants block the binding of  CGRP to the CGRP receptor quickly, which then stops the migraine. CGRP monoclonal antibodies work slower over time to keep CGRP from binding to the receptors in the brain, thus reducing the odds of CGRP triggering migraines.

CGRP monoclonal antibodies are used for the prevention of migraines. They are injected once monthly by self injection or once quarterly by IV infusion to avoid breaking down in the stomach. They tend to take longer to work, but do work faster than historical oral migraine preventive classes such as antiseizure, antidepressant, and antihypertensive medications. They have very few interactions with other drugs or harmful side effects, and are generally very well tolerated. They are discussed further here.

Gepants are faster acting and are taken orally. They are used to stop migraines once the pain starts (abortive or “as needed” medicines), but some are also FDA approved for preventing migraines. They are metabolized in the liver so there is the potential for some side effects and drug interactions, more so than with CGRP monoclonal antibodies.

Your doctor will look at a wide variety of different factors to determine whether or not gepants or CGRP monoclonal antibodies are a good fit. Keep in mind that there are many other options besides these newer medicine classes as well. If you are looking for pills, you will likely be prescribed Nurtec to take every other day or Qulipta once every day for migraine prevention, if your migraine frequency is high enough. Nurtec is unique in that it can be used as a migraine preventive or a migraine abortive (as needed) medication, or both. Some people opt for a one-time monthly CGRP monoclonal antibody self-injection, which will be either Aimovig, Emgality, or Ajovy. Another option on the market that will minimize the amount of time you have to go to the doctor is an IV option called Vyepti, which is administered quarterly in a 30 minute infusion.

Your options will likely vary based upon any medication that you are currently taking or any preexisting conditions that you may have, as well as the migraine pattern. 

One of the newest options for migraines and headaches is Qulipta. This was approved by the FDA in September 2021. Qulipta’s primary goal is to serve as a preventative daily treatment for migraines in adults. A new nasal spray gepant called Zavegepant is anticipated to be coming out sometime in the near future and is expected to be used as a migraine abortive.

If you suffer from chronic migraines or high frequency episodic migraines you might be a good candidate for monoclonal antibody treatment. A chronic migraine is defined as having at least 15 headaches each month, with 8 of those days including headaches with migraine features, lasting for at least 3 months. Monoclonal antibodies are also a good option for those who take other types of medications and want to minimize drug interactions.

If you are experiencing migraines, you have a plethora of different options to try. If you have more concerns other than just taking medication via pill form or via injection. Here are some of the things to keep in mind:

  • Depending on the patient, with either gepants or antibodies, a 75% to 100% reduction in monthly migraines could be possible in some patients. 
  • Each drug has small side effects that have been reported in studies. The most common side effect among some gepants and some monoclonal antibodies is constipation, but these occur in a small fraction of people. Some other rare side effects include nasopharyngitis, hypersensitivity, nausea, stomach discomfort, cramps, decreased appetite, and fatigue.
  • Everyone responds to medications differently, so your doctor will help you make the best choice to help you treat your migraines.

Dr. Eric Baron

Dr. Eric P. Baron is a staff ABPN (American Board of Psychiatry and Neurology) Board Certified Neurologist and a UCNS (United Council for Neurologic Subspecialties) Diplomat Board Certified in Headache Medicine at Cleveland Clinic Neurological Institute, Center for Neurological Restoration – Headache and Chronic Pain Medicine, in Cleveland, Ohio. He completed his Neurology Residency in 2009 at Cleveland Clinic, where he also served as Chief Neurology Resident. He then completed a Headache Medicine Fellowship in 2010, also at Cleveland Clinic, and has remained on as staff. He is also a Clinical Assistant Professor of Neurology at Cleveland Clinic Lerner College of Medicine of Case Western Reserve University. He has been repeatedly recognized as a “Top Doctor” as voted for by his peers in Cleveland Magazine, and has been repeatedly named one of "America's Top Physicians". He is an author of the popular neurology board review book, Comprehensive Review in Clinical Neurology: A Multiple Choice Question Book for the Wards and Boards, 1st and 2nd editions, and has authored many publications across a broad range of migraine and headache related topics. To help patients and health care providers who do not have easy access to a headache specialist referral due to the shortage in the US and globally, he created and manages the Virtual Headache Specialist migraine, headache, and facial pain educational content, blog, and personalized headache and facial pain symptom checker tool. You can follow his neurology, headache, and migraine updates on Twitter @Neuralgroover.