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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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.