Posts Tagged "Nurtec ODT"

Last updated on September 17th, 2021 at 04:53 am

WHAT ARE THE CGRP MIGRAINE MEDICATIONS AND HOW ARE THEY USED?

@Neuralgroover

What is CGRP (Calcitonin Gene Related Peptide)?

During a migraine attack, the trigeminal nerves release a variety of inflammatory proteins. One of the main proteins is called CGRP (calcitonin gene related peptide). CGRP has been studied since the early 1980s when it was discovered. It was found throughout the trigeminovascular system and trigeminal cranial nerves which transmit pain in the head and face. Therefore, a role in migraine was suspected. The trigeminal nerves are central to causing migraine as explained here. The trigeminal nerves and their associated electrical circuitry throughout the brain, brainstem, and arteries in the brain is called the trigeminovascular system. This system is the basis and an “on switch” for migraine.

In the early 1990s it was shown that CGRP was released by the trigeminal nerves and levels increased during an acute migraine attack. In 2004, a CGRP antagonist (blocks the binding of CGRP to its receptor) was shown to abort (stop) an acute migraine attack, and decrease CGRP levels. Subsequent preventive migraine studies done since 2014 with a CGRP antibody to block the effects of CGRP continued to show reduction in migraine frequency and severity.

 

CGRP causes inflammation around the brain and cerebral arteries (“sterile inflammation”) in the dural membrane surrounding the brain, intensifies pain signals, enhances transmission of pain signals through the trigeminal nerves into the brainstem and into the brain, and causes dilation of the cerebral arteries through the dural membrane. Trigeminal nerve endings surround these arteries. The dilation of these arteries triggers these trigeminal nerve endings and this leads to further increasing pain signals. Think of the process like a painful meningitis, minus the infection.

 

The result of these steps is intense migraine pain (as you are unfortunately very familiar with). So, if we can block these steps of migraine pain, the attack should be aborted quickly, and not as severe. That’s the thinking here, and that’s where the CGRP medications (gepants and CGRP monoclonal antibodies) come into play, as discussed below.

 

CGRP MEDICATIONS USED TO ABORT MIGRAINE (TAKEN AS NEEDED)

Abortive migraine medications are medications taken at the onset of the migraine with a goal of lessening the duration and severity of the migraine attack. Historically, the options have included NSAIDs, ergots, triptans, and neuromodulatory devices.

 

The gepants were the first new medicine class to emerge as new migraine abortive options (FINALLY!!!) since the triptans became available in 1992. There are currently 2 oral pill gepant abortive options available. They are Ubrelvy (Ubrogepant), and Nurtec ODT (orally dissolvable tablet) (Rimegepant). These 2 gepants are discussed and compared in much greater detail here. Zazegepant will be the 3rd abortive gepant, and will be the 1st nasal spray gepant option available. It is in ongoing clinical trials currently.

 

How does Nurtec ODT and Ubrelvy (gepants) work?

Gepants work as CGRP receptor antagonists, which means they directly block (antagonist) the CGRP receptor. This results in the medication “blocking” the CGRP inflammatory protein from sticking to the CGRP receptor to activate it, and thus prevents it from “turning on” the pathways of pain described above.

 

So, you get reversal of cerebral vasodilation, which decreases the firing off of the trigeminal nerves. Notably, the gepants do this in a way that does not cause vasconstriction, in contrast to the triptans. Thus, they are felt to be safe in those with cardiovascular or cerebrovascular disease (as opposed to the triptans).

 

By blocking the CGRP receptor, you also get reversal of the neurogenic inflammation going on through the brain and around the arteries, and you block the electrical transmission of migraine pain from traveling from the trigeminal nerves into the brainstem, and ultimately into the brain.

 

The other huge benefit of the triptans compared to all other abortive options is that they do not cause medication overuse headache (rebound headache)!

 

What are the side effects of Nurtec ODT and Ubrelvy?

The side effect profile of the gepants is minimal and similar to placebo. The most common side effects of gepants are very low risk of nausea for Nurtec ODT and low risk of nausea and mild sedation with the higher dose of Ubrelvy. Side effects are discussed in more detail here.

 

In addition, there is no interaction with using them and triptans, NSAIDs, or other acute meds in case they happen to be taken close together.

 

Compared to other abortive medications such as the triptans and NSAIDS, these medications are not associated with medication overuse headache (rebound headache), which is great! They also have no addiction potential.

 

Compared to the triptans and ergots, these medications are NOT contraindicated in patients with stable cardiovascular or peripheral vascular disease or risk factors because they do not cause vasoconstriction (narrowing) of the arteries, which is a HUGE benefit.

 

Triptans are also contraindicated in patients with visual snow, persistent migraine aura, and migrainous stroke (infarction). However, gepants are felt to be safe for these patients, as well as those with hemiplegic migraine and migraine with brainstem aura (previously called basilar migraine). There are many patients who have been stuck without safe options since they have been unable to use standard therapies such as triptans due to other medical problems such as heart disease. So, we finally have a safe alternative for them, which is a highlight of these medications.

 

Can Nurtec ODT and Ubrelvy be used in pregnancy and breastfeeding?

Safety of these medications in pregnancy or breastfeeding is unknown because they haven’t been studied, and therefore are not recommended.

 

Are there drug interactions with Nurtec ODT and Ubrelvy (gepants) and other medications?

The primary drug interactions to be aware of with these medications are when used with other medications that are metabolized by the liver enzyme system called CYP3A4. Many commonly used medications are metabolized by this system. Strong or moderate inhibitors of CYP3A4 (which slow down the metabolic drug breakdown) will cause an increase in gepant blood levels. Strong or moderate inducers of CYP3A4 (which increase the metabolic drug breakdown) will cause a decrease in gepant blood levels and possibly decreased effectiveness. These medications should be avoided in patients with severe liver disease or end stage kidney disease such as those on dialysis.

CGRP MEDICATIONS USED TO PREVENT MIGRAINE

Preventive migraine treatments are used to lessen the frequency and/or severity of migraine attacks. Preventive treatments include a variety of daily pill medications, neuromodulatory devices, herbal and natural supplements and vitamins, yoga and meditation, acupuncture and acupressure. All of the medications used for migraine prevention have always been “adopted” from other specialties. In other words, these were medicines made for other purposes (such as antidepressants, antiseizure, anti-blood pressure meds), but eventually some were also found to be useful for migraine prevention.

 

There has never been a medicine engineered and created purely and only for migraine prevention. However, that changed in 2018 when the migraine preventive landscape changed abruptly and significantly. The 1st medication class designed purely and only for migraine prevention become available, called the CGRP monoclonal antibodies (mAbs). There are currently 4 CGRP mAb treatment options. They are Aimovig (Erenumab), Emgality (Galcanezumab), Ajovy (Fremenazumab), and Vyepti (Eptinezumab).

 

These medications either target the CGRP receptor (Aimovig), or the CGRP protein (Emgality, Ajovy, Vyepti). The result of “blocking” the CGRP protein or CGRP receptor prevents the CGRP pathways of pain from “turning on”, as discussed above and here. Clinically, some patients tend to respond better to the CGRP receptor blockade, whereas others tend to do better with binding the CGRP protein itself. There is not really any data on this in terms of who may respond to which type of CGRP mAb target, but I’m sure it will be studied further eventually.

 

Aimovig, Emgality, and Ajovy are all once monthly self-injections (push button autoinjection), although Ajovy also has the option of quarterly injections (3 injections every 3 months). Vyepti is the only IV (intravenous form) and is done by 30-minute IV treatment every 3 months. These individual CGRP mAbs are discussed and compared in much greater detail here.

 

What are the side effects of the CGRP mAbs (Aimovig, Emgality, Ajovy, Vyepti)?

Compared to most other medications used for migraine prevention historically, the side effects of the CGRP mAbs are very low. The most common side effects reported (at a very low rate) are mild upper respiratory infections and minor injection site reactions. Aimovig has a slightly increased risk of constipation and possible mild increase in high blood pressure for some patients. These have little to no drug interactions and do not affect the liver or kidneys. Data show no immunological (they do not suppress or alter the immune system because they do not have a target within the immune system), cardiovascular, or neurological safety concerns of significance.

 

Can the CGRP mAbs (Aimovig, Emgality, Ajovy, Vyepti) be used in pregnancy and breastfeeding?

There is no data to answer this question yet. However, CGRP is suspected to play a possible role in regulating uteroplacental blood flow, myometrial and uterine relaxation, and in maintaining normal gestational blood pressure. Since the mAbs have a long half-life and can last in the system for 5 months, it is recommended to stop it about 6 months prior to pregnancy planning. The CGRP mAbs are also not recommended to use during breast-feeding since we do not have enough safety data at this time.

 

Nurtec ODT and gepants for migraine prevention.

The CGRP mAbs have been a major step forward for migraine prevention. However, up to this point, we still have not had an oral pill that has been engineered and created purely and only for migraine prevention (not “adopted” from a different medicine class as mentioned above).

 

That was until now, with development of the gepants (discussed above). On 5/27/21, Nurtec ODT (Rimegepant) made history as the first and only FDA approved medication for BOTH abortive and preventive migraine treatment simultaneously, and the only option with this flexibility and is discussed in greater detail here!

 

The perspective behind this is that migraine is a fluid and variable disease, fluctuating between periods of episodic migraine (1-14 headache days per month), and other periods of chronic migraine (15 or more headache days per month). So, having a medicine that can function as both types of treatment, depending on what type of phase the migraine is in (episodic or chronic) opens up an entirely new flexible treatment paradigm and approach which we have never had up to this point.

 

So essentially, taking Nurtec ODT every other day could be used as an ongoing daily preventive strategy (the long half-life of 11 hours allows for this spread-out dosing) when the migraine is in a high frequency to chronic migraine phase. If it evolves back into a lower frequency episodic migraine pattern, it can then just be used abortively only when needed for a migraine attack.

 

This new flexible dosing option of Nurtec ODT could also be used as a “mini-prophylaxis” within the month. For example, if patients know they are approaching a predictable migraine trigger, such as menstrual migraine, barometric trigger from an airplane trip, upcoming stressful event such as an exam, etc., the medication could possibly be taken daily or every other day starting a few days before the anticipated trigger, and stopping it a day or so after the trigger is no longer present. Unlike other migraine preventive pill treatments which take 4-6 weeks to start working and 2-3 months to see full effect, the gepants work fast and this would allow this potential treatment option to begin working immediately. In fact, studies show that migraine frequency dropped by 30% within the first week alone of preventive use.

 

Atogepant is the 2nd gepant that will be used as a daily preventive pill only and is pending FDA approval, but is anticipated soon.

 

Can the preventive CGRP mAbs (Aimovig, Emgality, Ajovy, Vyepti) be used with the CGRP abortive gepant medications (Nurtec ODT, Ubrelvy)?

Can I use Aimovig with Nurtec ODT? Can I use Aimovig with Ubrelvy? Can I use Emgality with Nurtec ODT? Can I use Emgality with Ubrelvy? Can I use Ajovy with Nurtec ODT? Can I use Ajovy with Ubrelvy? Can I use Vyepti with Nurtec ODT? Can I use Vyepti with Ubrelvy? These are very common questions. Unfortunately, there aren’t many studies so far to clarify this, although I’m sure these questions will be studied and clarified in the near future. The gepants and the CGRP mAbs have much different structures, molecule sizes, and metabolism.

 

So theoretically, it would make sense that using an abortive CGRP medication (gepant) on top of a CGRP preventive medication (CGRP mAb) would give synergistic (working together) benefit. Using a CGRP preventive medication targeting the CGRP protein (Emgality, Ajovy, Vyepti) and a CGRP abortive medication targeting the CGRP receptor (Nurtec ODT, Ubrelvy) seems like a very sensible idea. Similarly, using a CGRP preventive medication targeting the CGRP receptor (Aimovig) combined with a CGRP abortive medication also targeting the CGRP receptor (Nurtec ODT, Ubrelvy) would make a lot of sense too. In fact, there are some limited studies which provide evidence that these medications used together do work better and are safe.

 

There was a publication of data from only a 2-patient cohort showing that the use of these acute and preventive CGRP migraine therapies together can be successful and safe. These two patients had been using Rimegepant (Nurtec ODT) in a long-term safety study and they had added Erenumab (Aimovig) once monthly injection as a preventive treatment. After Aimovig was added, patient 1 had 100% relief for 7 of 7 acute migraine attacks treated with Nurtec. Patient 2 had 100% relief for 9 of 9 acute migraine attacks treated with Nurtec. So, the combination of using Nurtec abortively in addition to using Aimovig preventively appeared to provide an even more effective acute migraine response. Larger studies to confirm the suspicion that they likely work together synergistically will be helpful.

 

There was a larger safety study publication which evaluated the acute treatment of migraine with Rimegepant while using a CGRP monoclonal antibody for the prevention of migraine. The CGRP mAbs used were Erenumab (Aimovig) (7 patients), Fremanezumab (Ajovy) (4 patients), and Galcanezumab (Emgality) (2 patients). The study determined that Rimegepant used as an acute migraine treatment in combination with CGRP mAbs for migraine prevention was well tolerated with no safety issues identified. The researchers concluded that the probability between these 2 classes (gepants and CGRP mAbs) was low, especially because they have entirely different pathways of drug metabolism. The gepants are metabolized in the liver, while the CGRP mAbs are metabolized and cleared in the reticuloendothelial system. They also concluded that existing evidence supports the safety of combined use, although further larger research was warranted.

 

Can the CGRP mAbs (Aimovig, Emgality, Ajovy, Vyepti) be used with Botox (Onabotulinumtoxin A) for chronic migraine?

The answer is yes. Insurance companies often present various hurdles to using preferred treatment options (the bane of my existence). One common issue for patients with chronic migraine who are receiving Botox injections is that most insurance companies will now make the patient choose between Botox or the CGRP mAb. There is of course no good scientific basis for this, other than the company doesn’t want to pay for both.

 

Actually, there is evidence that using Botox with the CGRP mAbs works better together than with either individually. An abstract presented at the American Headache Society Annual Scientific meeting in June 2020 showed that in patients with chronic migraine and a baseline frequency of 25.7 days per month, the frequency dropped to 14.8 days with Botox, and 9.1 days with Botox plus a CGRP mAb.

 

Can I still use my CGRP mAb (Aimovig, Ajovy, Emgality, Vyepti) with the Covid-19 vaccine?

This hasn’t been a reported issue thus far. There is no current evidence for an interaction between the Covid-19 vaccine and CGRP mAbs, the same as any other vaccine. This has also been stated by the American Migraine Foundation. Patients receiving CGRP mAbs were not excluded from the Covid-19 vaccine trials. There is no evidence at this time that these treatments cannot be used along with receiving Covid-19 vaccination, nor do they need to be delayed or timed any differently in relation to receiving Covid-19 vaccination.

 

Most physicians feel that there should theoretically be no interaction or contraindication to receiving either of these treatments in relation to Covid-19 vaccination because they are entirely different proteins with different mechanisms of action. The Covid-19 vaccine stimulates the immune system to form antibodies against the virus, should you encounter it. The CGRP mAbs do not have any significant influence on the immune system (they do not cause immunosuppression, etc.).

 

Rarely, the immune system of some patients can form neutralizing antibodies against the CGRP mAbs, and this can weaken the effectiveness of these treatments in their ability to decrease migraine frequency and severity. However, this rarity really has nothing to do with the mechanism and how the Covid-19 vaccine works. So, it is not felt that the Covid-19 vaccine will lessen the effectiveness of these treatments, nor will these treatments lessen the effectiveness of the Covid-19 vaccine.

 

Notably, there have been just a few isolated reports of dermal fillers used in dermatology causing some facial swelling in association with Covid-19 vaccination, but not with Botox or the CGRP mAbs. These reports were with the Moderna Covid vaccine and resolved with steroids and/or antihistamines. The topic of Covid-19 headache and Covid-19 vaccination is discussed further here.

 

IF YOU HAVE HEADACHE, MIGRAINE, OR FACIAL PAIN AND ARE LOOKING FOR ANSWERS ON ANYTHING RELATED TO IT, A HEADACHE SPECIALIST IS HERE TO HELP, FOR FREE!

FIRST, LET’S DECIDE WHERE TO START:

IF YOU HAVE AN EXISTING HEADACHE, MIGRAINE, OR FACIAL PAIN DIAGNOSIS AND ARE LOOKING FOR THE LATEST INFORMATION, HOT TOPICS, AND TREATMENT TIPS, VISIT OUR FREE BLOG OF HOT TOPICS AND HEADACHE TIPS HERE. THIS IS WHERE I WRITE AND CONDENSE A BROAD VARIETY OF COMMON AND COMPLEX  MIGRAINE AND HEADACHE RELATED TOPICS INTO THE IMPORTANT FACTS AND HIGHLIGHTS YOU NEED TO KNOW, ALONG WITH PROVIDING FIRST HAND CLINICAL EXPERIENCE FROM THE PERSPECTIVE OF A HEADACHE SPECIALIST.

IF YOU DON’T HAVE AN EXISTING HEADACHE, MIGRAINE, OR FACIAL PAIN DIAGNOSIS AND ARE LOOKING FOR POSSIBLE TYPES OF HEADACHES OR FACIAL PAINS BASED ON YOUR SYMPTOMS, USE THE FREE HEADACHE AND FACIAL PAIN SYMPTOM CHECKER TOOL DEVELOPED BY A HEADACHE SPECIALIST NEUROLOGIST HERE!

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Last updated on October 21st, 2021 at 11:46 pm

NURTEC (RIMEGEPANT) VS. QULIPTA (ATOGEPANT) FOR MIGRAINE PREVENTION. THE GEPANTS AREN’T JUST FOR ABORTIVE TREATMENT ANYMORE! 

@Neuralgroover

BACKGROUND

The gepants were the first to emerge as new migraine abortive options, and the first new migraine specific abortive class since the triptans came to market in 1992. The first to become available was Ubrogepant (Ubrelvy) from Allergan in January 2020. Then Rimegepant (Nurtec ODT (orally dissolvable tablet)) became available by Biohaven shortly after in February 2020. The gepants have been game changers in the migraine abortive arena. However, they are now bringing their benefits to the migraine preventive realm, following a mind-blowing trifecta collision of the worlds of gepants, abortive and preventive therapy with Rimegepant (Nurtec ODT) and Atogepant (Qulipta)! These two medications are compared head to head in the table below.

 

On 5/27/21, Nurtec ODT made history as the first and only FDA approved medication for BOTH abortive and preventive migraine treatment simultaneously, and the only option with this flexibility! More recently, on 9/28/21, Qulipta (Atogepant) became the second oral CGRP preventive gepant medication to become FDA approved for migraine prevention. It is taken once daily. So these 2 options have become the first oral CGRP preventive medication options. They are both of the gepant medication family, which is different than the CGRP mAb family, but none the less now offer an oral alternative to once monthly CGRP monoclonal antibody injections.

 

I can hear you now. Rimegepant (Nurtec ODT) for migraine prevention? Atogepant for migraine prevention? Yes, you heard correctly. Are these available yet? We’ll discuss this and these new options a bit further down.

 

HOW DO THE GEPANTS WORK?

To review, during a migraine attack, the trigeminal nerves release a variety of inflammatory proteins. One of the main proteins is called CGRP (calcitonin gene related peptide). CGRP causes inflammation around the brain and cerebral arteries (“sterile inflammation”) in the dural membrane surrounding the brain, intensified pain signals, enhanced transmission of pain signals through the trigeminal nerves into the brainstem and into the brain, and dilation of the cerebral arteries through the dural membrane, which in turn leads to further increasing pain signals via the trigeminal nerve endings covering the cerebral arteries. The result is intense migraine pain (as you are unfortunately very familiar with). So, if we can block these steps of migraine pain, the attack should be aborted quickly, and not as severe. That’s the thinking here, and that’s where the CGRP medications (gepants and CGRP monoclonal antibodies) come into play.

 

The gepants work as CGRP receptor antagonists, which means they directly target and block (antagonist) the CGRP receptor. This results in the medication “blocking” the CGRP inflammatory protein from sticking to the CGRP receptor to activate it, and thus prevents it from “turning on” these pathways of migraine pain. So, you get reversal of cerebral vasodilation, which decreases the firing off of the trigeminal nerves, and cessation of electrical pain signals. Notably, the gepants do this in a way that does not cause vasconstriction, in contrast to the triptans. Thus, they are felt to be safe in those with cardiovascular or cerebrovascular disease (as opposed to the triptans which can not be used in these patients). By blocking the CGRP receptor, you also get reversal of the neurogenic inflammation going on through the brain and around the arteries, and you block the electrical transmission of migraine pain from traveling from the trigeminal nerves into the brainstem, and ultimately into the brain.

 

GEPANTS FOR MIGRAINE PREVENTION

Rimegepant (Nurtec ODT) and Ubrogepant (Ubrelvy) were created and FDA approved for the abortive (as needed) treatment of migraine in 2020. The goal of migraine abortive treatment is to stop individual migraine attacks at onset so the migraine does not reach full severity, ends quickly, and your function is restored and maintained. We want you to avoid having to go lay down and miss that family/social event, work meeting, or whatever else you had planned, and instead end up spending the whole day in a dark quiet bedroom. As opposed to conventional migraine abortives such as triptans, NSAIDs, and other analgesics, the gepants have the unique characteristic that they do not cause rebound headache (medication overuse headache), which is why they have also been evaluated as daily preventive medications as we’ll discuss below.

 

Abortive treatments are different than migraine preventive treatments, which are a continuous treatment (not just taken as needed) meant to lessen the frequency and/or severity of migraine attacks (hopefully both). Conventional preventive treatment options include a daily pill, a monthly/quarterly CGRP monoclonal antibody (mAb) (Aimovig, Ajovy, Emgality, Vyepti) injectionneuromodulation devices, Botox injections, or alternative treatments such as vitamins and supplements, acupuncture, acupressure and pressure points, or yoga and meditation. The goal of migraine preventive treatment is to lessen the frequency and/or severity of migraine attacks and are discussed in more detail here. If you have migraine, you want to have both a good abortive and preventive treatment plan to lessen migraine’s nasty habit of interfering and disrupting life and function.

 

Notably, for many decades, we have never had migraine specific preventive treatment. What I mean is that the treatments we have always used have been adopted from and limited to medications including antiseizure, antidepressant/anxiety, and blood pressure medications. Although many patients certainly do well with these preventive options, none of these medicines have been scientifically engineered and created specifically to target migraine pathophysiology for migraine prevention. In addition, many patients do not tolerate the side effects or cannot use many of these medications due to other medical conditions. So a lot of patients have been stuck without adequate preventive migraine therapy. That was until 2018 with the first once monthly self-injection CGRP monoclonal antibody (mAb) Erenumab (Aimovig) came to market, and was followed by 3 more CGRP mAbs; Fremanazumab (Ajovy), Galcanezumab (Emgality), and Eptinezumab (Vyepti).

 

The CGRP mAbs have been a major step forward for migraine prevention. However, up to this point, we still have not had an oral pill that has been engineered and created purely and only for migraine prevention (not “adopted” from a different medicine class such as the anti-seizure, antidepressant, and anti-blood pressure pills). That was until now. These new oral gepant medications will be the first in history to assume this new role, finally giving migraine patients a new unique treatment option to add to their war chest.

 

The two gepants being targeted for preventive migraine therapy are Rimegepant (Nurtec ODT) from Biohaven and Atogepant (Qulipta) from Allergan/Abbvie. On 5/27/21, Nurtec ODT made history as the first and only FDA approved medication for BOTH abortive and preventive migraine treatment simultaneously, and the only option with this flexibility! The perspective and reasoning behind this is that migraine is truly a fluid and variable disease, commonly fluctuating between periods of episodic migraine (1-14 headache days per month), and other periods of chronic migraine (15 or more headache days per month). So having a medicine that can function as both types of treatment, depending on what type of phase the migraine is in (episodic or chronic) opens up an entirely new flexible treatment paradigm and approach which we have never had up to this point.

 

More recently, on 9/28/21, Qulipta (Atogepant) became the second oral CGRP preventive gepant medication to become FDA approved for migraine prevention (not dually approved for both abortive and preventive). It is the first gepant that was designed and studied purely for only migraine prevention. It is taken once daily. So, Nurtec ODT and Qulipta have become the first oral CGRP preventive medication options. They are both of the gepant medication family, which is different than the CGRP mAb family, but none the less now offer an oral alternative to once monthly injections.

 

Compared to standard historical oral preventive options, the gepant preventives Nurtec and Qulipta work extremely quick (within even a day!) as detailed below. So you are not having to wait the usual 4-6 weeks to start working and 2-3 months to see full effect as oral preventives have typically required.

 

Yes, I know your mind has just been blown. Let’s discuss them both and the currently available data, which can be found on each company’s website.

RIMEGEPANT ODT (Nurtec ODT)

Rimegepant ODT 75 mg every other day was studied and published in the preventive treatment of both episodic (4-14 days per month) and chronic migraine (15-30 days per month) during a 12-week double-blind randomized placebo-controlled treatment which included 747 patients. Migraine frequency was first observed and tracked for 4 weeks. Then, the 12 week treatment phase began. Patients were allowed to take 1 preventive migraine medication, (excluding CGRP receptor antagonists and CGRP monoclonal antibodies), as long as they were on a stable dose for at least 3 months and did not change it during the study. Patients were instructed to take 1 tablet every other day (which was either rimegepant or placebo) for migraine prevention. They were allowed to use rescue medications including triptans, nonsteroidal anti-inflammatory drugs (NSAIDs), and other typical analgesics. Rimegepant was not permitted as a rescue medication during the 12-week double-blind treatment phase. Migraine preventive benefits were seen in patients with episodic migraine, as well as those with and without a history of chronic migraine. Detailed results can be seen in the table below comparing Nurtec vs. Qulipta for migraine prevention.

 

The primary endpoint of this study:

-Change in monthly migraine days from the observation baseline compared to weeks 9-12. The study met its primary endpoint, demonstrating a statistically significant reduction from baseline in monthly migraine days in patients treated with Rimegepant compared with placebo. Patients receiving rimegepant 75 mg every other day (N=348) experienced a statistically significant reduction of 4.3 monthly migraine days for Rimegepant compared to a 3.5 day reduction in the placebo group (N=347).

 

Secondary endpoints included:

-50% or more reduction in monthly moderate to severe migraine days in weeks 9-12. Rimegepant was superior to placebo. 49% of patients taking Rimegepant had a 50% or more reduction in moderate to severe migraine days compared to 41% in placebo.

-Change in the mean monthly migraine days across the full treatment phase (weeks 1-12). Rimegepant was superior to placebo. Patients taking Rimegepant had 3.6 less monthly migraine days compared to 2.7 less days in placebo.

-Rescue medication days per month in weeks 9-12. There were slightly less rescue medication days per month in the Rimegepant group (3.7 days) compared to placebo (4 days), but this was not statistically superior.

-Change in monthly migraine days in the first 4 treatment weeks (weeks 1-4). Rimegepant was superior to placebo. Patients taking Rimegepant had 2.9 less monthly migraine days compared to 1.7 less days in placebo..

 

Preventive benefits began fast. Within the 1st week, there was a 30% drop in migraines (compared to 9.4% drop in the placebo group).

 

The safety and tolerability of rimegepant across the 12-week double-blind treatment phase was similar to that of placebo. Adverse events (AEs) occurring in greater than 2% of participants in the rimegepant treated group were nasopharyngitis (4%), nausea (3%), urinary tract infection (2%), and upper respiratory tract infection (2%). Nearly all AEs were mild or moderate in intensity. No treatment-related serious AEs were reported in the rimegepant group. Discontinuations due to an AE were low in both groups (rimegepant 2% and placebo 1%). Four (1%) participants who were treated with rimegepant and 2 (1%) participants who were treated with placebo experienced transaminase (ALT or AST) elevations greater than 3x upper limit of normal (ULN). One participant in the rimegepant group had asymptomatic elevation of transaminases with ALT greater than 10x ULN; alkaline phosphatase and bilirubin levels remained within normal limits. One participant in the rimegepant group had bilirubin levels greater than 2x ULN and was diagnosed with Gilbert’s syndrome after genomic testing.

 

A 52-week open-label extension phase followed the above double-blind study. Patients dosed rimegepant 75 mg every other day and were allowed to take up to one dose of rimegepant 75 mg as needed on non-scheduled dosing days to treat migraine attacks as well. The data from this will be forthcoming.

 

Personally, I think this opens many treatment possibilities that we haven’t had available up to this point. For one thing, taking it every other day could be used as an ongoing daily preventive strategy (the long half life allows for this spread out dosing) when the migraine is in a high frequency to chronic migraine phase. If it evolves back into a lower frequency episodic migraine pattern, it can then just be used abortively only when needed for a migraine attack. This new flexible dosing option could also be used as a “mini-prophylaxis” within the month. For example, if patients know they are approaching a predictable migraine trigger, such as menstrual migraine, barometric trigger from an airplane trip, upcoming stressful event such as an exam, etc., the medication could possibly be taken daily or every other day starting a few days before the anticipated trigger, and stopping it a day or so after the trigger is no longer present. Unlike other migraine preventive treatments which take 4-6 weeks to start working and 2-3 months to see full effect, the gepants work fast and this would allow this potential treatment option to work. Headache specialists often do this “mini-prophylaxis” for the above mentioned scenarios with long acting triptans such as Frovatriptan and Naratriptan. However, for some people, this could lead to having to use it more than 10 days per month on average, which could then start to fuel rebound headache (medication overuse headache). The nice thing about the gepants is that there is no rebound headache associated with them, so this would also not be a risk when used for mini-prophylaxis.

 

ATOGEPANT (Qulipta)

Atogepant 10 mg, 30 mg and 60 mg doses once daily were studied in the preventive treatment of episodic migraine (4-14 days per month) during a 12-week double-blind randomized placebo-controlled treatment which included 910 patients. Detailed results can be seen in the table below.

 

Atogepant met the primary endpoint of statistically significant reduction from baseline in mean monthly migraine days, compared to placebo, for all doses evaluated across the 12-week treatment period. Patients treated in the 10 mg/30 mg/60 mg atogepant arms experienced a decrease of 3.69/3.86/4.2 days per month averaged over the 12 weeks, respectively, compared to placebo at 2.48 days less. By weeks 9-12, there was a 4-4 day reduction in migraine days with 60 mg. On average across the 12 week trial, patients on the 60 mg dose had a 54% reduction in monthly migraine days!

 

It worked very fast as well. The day following the first 60 mg dose, patients were 51% less likely to have a migraine. Within the 1st week there was a 53% reduction in migraines (compared to 15% in placebo)!

 

Atogepant also showed statistically significant improvements in six secondary endpoints in the 30 mg and 60 mg once-daily treatment arms. Additional secondary endpoints measured across the 12-week treatment period included change from baseline in monthly headache days, mean monthly acute-medication use days, and mean monthly performance of daily activities and physical impairment domain scores. The 30 mg and 60 mg doses resulted in statistically significant improvements in all secondary endpoints, while treatment with the 10 mg dose resulted in statistically significant improvements in four out of the six secondary endpoints.

 

A key secondary endpoint measured the proportion of patients that achieved at least a 50% reduction in monthly migraine days across the 12-week treatment period. Results showed that across the 12 week trial, 56%/59%/61% of patients in the 10 mg/30 mg/60 mg atogepant arms, respectively, achieved a 50% or more reduction in migraine days compared to 29.0% of patients in the placebo arm. By weeks 9-12, 71% of patients on 60 mg had reduced their monthly migraine days by 50% or more!!

 

The trial also assessed the proportion of patients that achieved a 75% or more reduction in monthly migraine days across the 12-week treatment period. Results showed that 30%/30%/38% of patients in the 10 mg/30 mg/60 mg atogepant arms, respectively, achieved a 75% or more reduction in monthly migraine days, compared to 11% of patients in the placebo arm. By weeks 9-12, 50% of patients on 60 mg had reduced their monthly migraine days by 75% or more!!

 

And they didn’t stop there. The trial then assessed the proportion of patients that achieved a 100% reduction in monthly migraine days across the 12-week treatment period. Yes, you read that correctly, they went to 0 migraines per month. Results showed that 8%/5%/8% of patients in the 10 mg/30 mg/60 mg atogepant arms, respectively, achieved a 100% reduction in monthly migraine days, compared to 1% of patients in the placebo arm. By weeks 9-12, 28% of patients on 60 mg had 100% reduction in monthly migraine days… complete resolution!! Amazing. We just aren’t used to seeing these kinds of results.

 

After the main trials were completed, they began a 52 week (1 year) open label trial (patients knew they were taking the medicine) where patients took 60 mg daily. The goal was to assess for further side effects or safety concerns, of which there were none. By the end of the trial, and after a continued decline in migraines, patients were averaging 71% less migraine days per month, which equated to 5.2 less migraine days per month on average.

 

No significant safety risks were observed. Serious adverse events occurred in 0.9% of patients treated in the atogepant 10 mg arm compared to 0.9% of patients in the placebo arm (so basically, no difference). No patients in the atogepant 30 mg or 60 mg treatment arms experienced a serious adverse event. The most common adverse events reported with a frequency ≥ 5% in at least one atogepant treatment arm, and greater than placebo, were constipation (6.9-7.7% across all doses vs. 0.5% for placebo), nausea (4.4-6.1% across all doses vs. 1.8% for placebo), and upper respiratory tract infection (3.9-5.7% across all doses vs. 4.5% for placebo). The majority of cases of constipation, nausea and upper respiratory tract infection were mild or moderate in severity and did not lead to discontinuation. There were no hepatic safety issues identified in the trial.

 

Nurtec ODT vs. Qulipta are compared in the following table. As I obtain additional data, this table will continue to be updated.

  Nurtec ODT (Rimegepant) Qulipta (Atogepant)
Medication Class Gepant Gepant
Mechanism of Action CGRP receptor antagonist CGRP receptor antagonist
Available dosing 75 mg orally dissolvable tablet 10 mg, 30 mg, 60 mg pill
Pills per prescription (standard, may be more depending on insurance) 16 30
Dosing frequency 1 dose every other day 1 dose daily
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

% 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%

% reduction of migraine days in weeks 1-12 75 mg: N/A

Placebo: N/A

10 mg: N/A

30 mg: N/A

60 mg: 54%

Placebo: 33%

% 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%

% of patients with a 75% or more decrease in monthly migraine days across weeks 1-12 75 mg: N/A

Placebo: 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%

% of patients with a 100% decrease in monthly migraine days across weeks 1-12 75 mg: N/A

Placebo: 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%

Time to peak plasma concentration TMAX 90 minutes 60-120 minutes
½ life 11 hours 11 hours
Notable side effects Nausea

75 mg: 2.7%

Placebo: 0.8%

 

Abdominal Discomfort

75 mg: 2.4%

Placebo: 0.8%

 

Nausea

10 mg: 5%

30 mg: 6%

60 mg: 9%

Placebo: 3%

 

Constipation

10 mg: 6%

30 mg: 6%

60 mg: 9%

Placebo: 1%

 

 

Somnolence/Fatigue

10 mg: 4%

30 mg: 4%

60 mg: 6%

Placebo: 3%

 

Decreased Appetite

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%

 

Can I use a CGRP monoclonal antibody (mAb) (Aimovig, Ajovy, Emgality, Vyepti) with the gepants (Nurtec, Ubrelvy)?

An insurance battle often ensues when trying to use the large molecule preventive CGRP mAbs with the small molecule abortive gepant medications (Nurtec, Ubrelvy), which also work by a CGRP mechanism. Insurance companies will often not allow these to be used together, but again, no good scientific basis. Actually, there is some limited evidence showing that these medications can work synergistically together, which would make sense when taking their mechanisms of action into account. Specifically, there was a publication of data from only a 2-patient cohort showing that the use of these acute and preventive CGRP migraine therapies together can be successful and safe. These two patients had been using rimegepant (Nurtec) in a long-term safety study and they had added erenumab (Aimovig) once monthly injection as a preventive treatment. After Aimovig was added, patient 1 had 100% relief for 7 of 7 acute migraine attacks treated with Nurtec. Patient 2 had 100% relief for 9 of 9 acute migraine attacks treated with Nurtec. So, the combination of using Nurtec abortively in addition to using Aimovig preventively appeared to provide an even more effective acute migraine response. Theoretically, it would make sense that benefit would be greater with both classes of medicines combined because they are entirely different types of medications targeting aspects of the same migraine pathway simultaneously (either targeting the CGRP receptor or the CGRP ligand protein). Larger studies to confirm the suspicion that they likely work together synergistically will be helpful.

 

There was a larger safety study publication which evaluated the acute treatment of migraine with Rimegepant while using a CGRP monoclonal antibody for the prevention of migraine. The CGRP mAbs used were Erenumab (Aimovig) (7 patients), Fremanezumab (Ajovy) (4 patients), and Galcanezumab (Emgality) (2 patients). The study determined that Rimegepant used as an acute migraine treatment in combination with CGRP mAbs for migraine prevention was well tolerated with no safety issues identified. The researchers concluded that the probability between these 2 classes (gepants and CGRP mAbs) was low, especially because they have entirely different pathways of drug metabolism. They also concluded that existing evidence supports the safety of combined use, although further larger research was warranted.

 

 

 

IF YOU HAVE HEADACHE, MIGRAINE, OR FACIAL PAIN AND ARE LOOKING FOR ANSWERS ON ANYTHING RELATED TO IT, A HEADACHE SPECIALIST IS HERE TO HELP, FOR FREE!

FIRST, LET’S DECIDE WHERE TO START:

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Last updated on October 4th, 2021 at 01:38 pm

AIMOVIG vs AJOVY vs EMGALITY vs VYEPTI. BATTLE OF THE CGRP MONOCLONAL ANTIBODY ANTAGONISTS; WHAT ARE THE DIFFERENCES AND WHICH IS BEST FOR YOU?

@Neuralgroover

Background

Aimovig vs. Ajovy, Aimovig vs. Emgality, Aimovig vs Vyepti, Ajovy vs. Emgality, Emgality vs. Vyepti, Ajovy vs. Vyepti. So many questions. so many answers. Let’s discuss them all. So it finally happened! The 1st migraine specific preventive medications FINALLY became available with the CGRP (calcitonin gene related peptide) monoclonal antibody (CGRP mAb) antagonists which first came to market in 2018. Prior to 2018, all of the migraine preventive medication options had been “adopted” from other specialties. For example, the 3 main categories of preventive medicines prior to 2018 were select evidence-based options within the anticonvulsant (antiseizure), antidepressant/antianxiety, and antihypertensive (blood pressure) medicine categories. These conventional migraine preventive treatments are certainly still used, can be very effective, and are discussed in much greater detail here. Migraine preventive therapies also include neuromodulation devices, Botox injections, or alternative treatments such as vitamins and supplements, acupuncture, acupressure and pressure points, or yoga and meditation. This blog article will discuss and compare the 4 new options of CGRP mAb medications; Aimovig (Erenumab), Ajovy (Fremanezumab), Emgality (Galcanezumab), and Vyepti (Eptinezumab).




CGRP plays a strong role in neurogenic inflammation in the nervous system and is involved in the transmission of pain. It is also a potent vasodilator (dilates blood vessels), and increases overexcitability of neurons, both factors of which increase the intensity of migraine pain. CGRP has been studied since the early 1980s when it was discovered. It was found throughout the trigeminovascular system and trigeminal cranial nerves which transmit pain, so a role in migraine was suspected. The trigeminal nerves and their associated electrical circuitry throughout the brain, brainstem, and arteries in the brain is called the trigeminovascular system. This system is the basis and “on switch” for migraine. In the early 1990s it was shown that CGRP was released by the trigeminal nerves and levels increased during an acute migraine attack. In 2004, a CGRP antagonist (blocks the binding of CGRP to its receptor) was shown to abort an acute migraine attack, and decrease CGRP levels. Subsequent studies including preventive migraine studies done since 2014 with a CGRP antibody to block the effects of CGRP eventually led to 3 FDA approved CGRP mAbs in 2018, and a 4th CGRP mAb FDA approved in 2020.

 

How are the CGRP mAbs made and what is the science behind them?

The CGRP mAbs are considered biologic drugs because they are made by the cells of living organisms. This is in contrast to conventional medications made by chemical synthesis. The 4 CGRP mAbs are all classified as “humanized” monoclonal antibodies. Humanized CGRP mAbs are made in a laboratory by combining part of a human antibody with a small part of a non-human (such as hamster or yeast) monoclonal antibody by a process called recombinant DNA technology. The non-human part of the antibody binds to the target antigen (in this case, either the CGRP ligand (protein) or CGRP receptor), and the human part makes it less likely to be seen as a “foreign antigen” destroyed by our immune system. To explain further, these humanized CGRP mAbs are produced and cloned repeatedly in non-human immune system living cells (hamster ovarian cells or yeast cells), ensuring that they are all of identical genetic material (monoclonal), and their protein structure is modified to increase their similarity to antibody structures produced naturally in humans.

As a review, antibodies are proteins made by living organism cells which bind unique parts of other proteins that are recognized as a “foreign” to that biologic system. For example, when your body is exposed to a virus or bacteria by infection or immunization, your body makes specific antibodies against that microbe to destroy it. If your body encounters that microbe in the future, it remembers it (immune response), and your antibodies attach to it to neutralize and destroy it.

 

How do the CGRP mAbs work for migraine?

The CGRP mAbs target either the CGRP receptor and block it (antagonist) to prevent the CGRP ligand (protein) from binding, or they target the CGRP ligand itself and prevent it from binding (sticking) to the CGRP receptor. Clinically, some patients tend to respond better to the CGRP receptor blockade, whereas others tend to do better with binding the CGRP ligand itself. There is not really any data on this in terms of who may respond to which type of CGRP mAb target, but I’m sure it will be studied further eventually. In general, the CGRP mAbs tend to all be quite effective. However, the point is if one type of CGRP mAb doesn’t work, it doesn’t mean the others won’t work either. I have seen many patients who did not respond to one type of CGRP mAb, but responded dramatically well to another. So, if you do not respond to one type of CGRP mAb target (such as the CGRP receptor), it may be worth trying another type of CGRP mAb target (such as the CGRP ligand). The bottom-line is don’t lose hope if one type doesn’t work well for you!

The CGRP mAbs are administered by injection or infusion because oral absorption is poor and degradation in the gastrointestinal system would inactivate the antibodies before they would even be able to enter the circulatory system. They are systemically absorbed by transport through the lymphatic system and into the blood. Metabolism occurs in the reticuloendothelial system, not the liver or kidneys.

 

How effective are the CGRP mAbs?

All 4 of the CGRP mAbs have shown excellent tolerability, safety, and superior effectiveness in migraine prevention when compared to placebo. Compared to oral preventive therapies which have been the mainstay for decades (discussed here), the CGRP mAbs work much faster and do not require a slow dose titration, as is done with most oral preventives. They are sometimes seen to be effective in just a few days, often within a month, and the data suggests that the longer a patient is on a CGRP mAb, the more effective it is. I typically recommend a minimum of at least 3 months, and if receiving some benefit at that point, at least 6 months is suggested.

The majority of CGRP mAb studies had at least 50% (half) of patients who were 50% responders (migraine days cut in half), which is great! In general, the CGRP mAbs provide an overall average net reduction of around 2 migraine days per month for episodic migraine and 4-6 days for chronic migraine. With that said, this number can be much higher depending on the patient and migraine characteristics being studied, such as baseline migraine frequency.

There are a group of patients that we see called “super responders” because they improve dramatically to having greater than 75% decrease in migraine days, and sometimes even no migraines. In the CGRP mAb studies, about 1/3rd of patients were “super responders”, with many them obtaining 100% reduction in migraine days. Although this is wonderful to see when it happens, it should not be the expectation or goal (nor should this be the goal with any preventive migraine treatment).

 

What are the CGRP mAb side effects and are they safe in pregnancy and breastfeeding?

Side effects are minimal, and very similar to placebo in most of the studies, which is great compared to the frequent side effects seen with most of the oral preventive pills we often use. The most common side effects are listed in the table below, but mild injection site reactions tend to be the most common reported side effect among the 3 subcutaneous self-injection CGRP mAbs. Cumulative data show no immunological (they do not suppress or alter the immune system because they do not have a target within the immune system), cardiovascular, or neurological safety concerns of significance. CGRP is suspected to play a possible role in regulating uteroplacental blood flow, myometrial and uterine relaxation, and in maintaining normal gestational blood pressure. Since the mAbs have a long half-life and can last in the system for 5 months, it is recommended to stop it about 6 months prior to pregnancy planning. The CGRP mAbs are also not recommended to use during breast-feeding since we do not have enough safety data at this time.

 

Can I still use my CGRP monoclonal antibody treatment (Aimovig, Ajovy, Emgality, Vyepti) with the Covid-19 vaccine? 

The short answer is that we need to gather more data on this, so check back periodically for updates. However, this hasn’t been a reported issue thus far. There is no current evidence for an interaction between the Covid-19 vaccine and CGRP mAbs, the same as any other vaccine. This has also been stated by the American Migraine Foundation. Patients receiving CGRP monoclonal antibodies (Aimovig, Ajovy, Emgality, Vyepti) were not excluded from the Covid-19 vaccine trials. There is no evidence at this time that these treatments cannot be used along with receiving Covid-19 vaccination, nor do they need to be delayed or timed any differently in relation to receiving Covid-19 vaccination. Most physicians feel that there should theoretically be no interaction or contraindication to receiving either of these treatments in relation to Covid-19 vaccination because they are entirely different proteins with different mechanisms of action. The Covid-19 vaccine stimulates the immune system to form antibodies against the virus, should you encounter it. The CGRP mAbs do not have any significant influence on the immune system (they do not cause immunosuppression, etc.). Rarely, the immune system of some patients can form neutralizing antibodies against the CGRP mAbs, and this can weaken the effectiveness of these treatments in their ability to decrease migraine frequency and severity. However, this rarity really has nothing to do with the mechanism and how the Covid-19 vaccine works. So, it is not felt that the Covid-19 vaccine will lessen the effectiveness of these treatments, nor will these treatments lessen the effectiveness of the Covid-19 vaccine.

Notably, there have been just a few isolated reports of dermal fillers used in dermatology causing some facial swelling in association with Covid-19 vaccination, but not with Botox or the CGRP mAbs. These reports were with the Moderna Covid vaccine and resolved with steroids and/or antihistamines. The topic of Covid-19 headache, Covid-19 vaccination, and the use of Botox is discussed further here.

 

Can I use a CGRP mAb (Aimovig, Ajovy, Emgality, Vyepti) with Botox injections?

Insurance companies often present various hurdles to using preferred treatment options (the bane of my existence). One common issue for patients with chronic migraine who are receiving Botox injections is that most insurance companies will now make the patient choose between Botox or the CGRP mAb. There is of course no good scientific basis for this, other than the company doesn’t want to pay for both. In fact, there is evidence that using Botox with the CGRP mAbs works better together than with either individually. An abstract presented at the American Headache Society Annual Scientific meeting in June 2020 showed that in patients with chronic migraine and a baseline frequency of 25.7 days per month, the frequency dropped to 14.8 days with Botox, and 9.1 days with Botox plus a CGRP mAb.

 

Can I use a CGRP mAb (Aimovig, Ajovy, Emgality, Vyepti) with the gepants (Nurtec, Ubrelvy)?

A similar insurance battle often ensues when trying to use the large molecule preventive CGRP mAbs with the small molecule abortive gepant medications (Nurtec, Ubrelvy), which also work by a CGRP mechanism. Insurance companies will often not allow these to be used together, but again, no good scientific basis. Actually, there is some limited evidence showing that these medications can work synergistically together, which would make sense when taking their mechanisms of action into account. Specifically, there was a publication of data from only a 2-patient cohort showing that the use of these acute and preventive CGRP migraine therapies together can be successful and safe. These two patients had been using rimegepant (Nurtec) in a long-term safety study and they had added erenumab (Aimovig) once monthly injection as a preventive treatment. After Aimovig was added, patient 1 had 100% relief for 7 of 7 acute migraine attacks treated with Nurtec. Patient 2 had 100% relief for 9 of 9 acute migraine attacks treated with Nurtec. So, the combination of using Nurtec abortively in addition to using Aimovig preventively appeared to provide an even more effective acute migraine response. Theoretically, it would make sense that benefit would be greater with both classes of medicines combined because they are entirely different types of medications targeting aspects of the same migraine pathway simultaneously (either targeting the CGRP receptor or the CGRP ligand protein). Larger studies to confirm the suspicion that they likely work together synergistically will be helpful.

 

There was a larger safety study publication which evaluated the acute treatment of migraine with Rimegepant while using a CGRP monoclonal antibody for the prevention of migraine. The CGRP mAbs used were Erenumab (Aimovig) (7 patients), Fremanezumab (Ajovy) (4 patients), and Galcanezumab (Emgality) (2 patients). The study determined that Rimegepant used as an acute migraine treatment in combination with CGRP mAbs for migraine prevention was well tolerated with no safety issues identified. The researchers concluded that the probability between these 2 classes (gepants and CGRP mAbs) was low, especially because they have entirely different pathways of drug metabolism. They also concluded that existing evidence supports the safety of combined use, although further larger research was warranted.

 

Notably, on 5/27/21, the oral pill Nurtec (Rimegepant) ODT made history as the first and only FDA approved medication for BOTH abortive and preventive migraine treatment simultaneously, and remains the only option with this flexibility. It also became the first oral CGRP preventive gepant medication with this approval. It is used as a migraine abortive once per 24 hours as needed for migraine, or as a migraine preventive by using it every other day. Both doses are a simple 75 mg dissolvable tablet. More recently, on 9/28/21, Qulipta (Atogepant) became the second oral CGRP preventive gepant medication to become FDA approved for migraine prevention. It is taken once daily. So these 2 options have become the first oral CGRP preventive medication options. They are both of the gepant medication family, which is different than the CGRP mAb family, but none the less now offer an oral alternative to once monthly injections.

 




Clinical comparisons of the CGRP mAbs

There are currently 4 CGRP mAbs available, and each is detailed and compared below in order of FDA approval and becoming available for use. There are some characteristics for each one which can be used to fine tune selection based on specific patient clinical perspectives. The bottom line is that the CGRP mAbs as a class are all very effective for the majority of patients. Ultimately, the one prescribed will often depend on insurance formulary preferences, but there are no “bad options” among them!

 

Aimovig (Erenumab)

Aimovig was the first of the CGRP mAbs to come on the scene. It is made by Amgen and was FDA approved for migraine prevention 5/17/18. The antibody is produced by recombinant DNA technology in Chinese hamster ovary cells. It is the only one thus far which targets the CGRP receptor rather that the CGRP ligand (protein) itself. Therefore, it binds to the receptor, blocking the ability of the CGRP ligand to bind to the receptor and activate the migraine. It is dosed by either a 70 mg or 140 mg once monthly subcutaneous autoinjector. Since Aimovig came out first, we have longer term data available for it. At close to 5 years on the 140 mg dose, 77% of patients had a 50% reduction in monthly migraine days, 56% of patients had a 75% reduction in monthly migraine days, and 33% of patients had a 100% reduction in monthly migraine days. The dose can be administered to the abdomen, arm, buttocks, or thigh areas.

In post-marketing observations, there have been some reports of hypersensitivity reactions (rash, allergic reactions, itching) in which most were not serious and occurred within hours of administration, and up to 1 week after. Constipation was noted in the studies to occur in a very small percentage (1% for 70 mg, 3% for 140 mg). In post-marketing observations, there have been further reports of constipation with serious complications as well. Constipation occurs after the first dose in the majority of patients who will have this side effect (keep in mind the vast majority do not). Regardless, if you already have problems with constipation, I typically suggest trying one of the other CGRP mAbs (although it doesn’t mean it still can’t be tried). Post-marketing observations have also shown some worsening of pre-existing hypertension or development of hypertension. This observation was most frequently reported within 7 days of administration. Most of these patients already had pre-existing hypertension, or risk factors for developing it.

There is an Aimovig coupon available on the company’s website in which most commercial insurance plans can get the medication for $5 per month, with the first 3 doses free.

 

Ajovy (Fremanezumab)

Ajovy was the 2nd of the CGRP mAbs to come along. It is made by Teva and was FDA approved for migraine prevention 9/14/18. It is produced by recombinant DNA technology in Chinese hamster ovary cells. It targets the CGRP ligand, rather than the CGRP receptor. It binds to the CGRP ligand, interfering with its ability to bind to the CGRP receptor and activate the migraine. It is dosed by either a 225 mg once monthly or 675 mg once quarterly autoinjector or syringe. The dose can be administered to the abdomen, arm, buttocks, or thigh areas. There have been some reports of hypersensitivity reactions (rash, allergic reactions, itching) as well, typically mild to moderate and occurred hours to 1 month after administration. Ajovy has the least potential for constipation, so if that is an ongoing significant issue for a patient, then I typically suggest trying Ajovy first. Ajovy also has the longest half-life, so if the patient tends to wear off early towards the end of the month, it may help to extend relief closer to the next monthly injection.

Of note, in the Ajovy chronic migraine studies, all patients receiving medication were given a loading dose of 675 mg for dose 1 followed by the standard 225 mg each subsequent month. However, this is not how it is normally dosed clinically for patients doing monthly treatments of 225 mg (no loading dose). Therefore, this initial loading dose could have potentially influenced some of the subsequent data.

There is an Ajovy coupon available on the company’s website in which most commercial insurance plans can get the medication for $5 per month.

 

Emgality (Galcanezumab)

Emgality was the 3rd of the CGRP mAbs to come along. It is made by Eli Lilly and was FDA approved for migraine prevention 9/26/18. Notably, it is the only one which also has FDA approval for prevention of episodic cluster headache, which was received on 6/4/19. It is produced by recombinant DNA technology in Chinese hamster ovary cells. It targets the CGRP ligand, rather than the CGRP receptor. Thus, it binds to the CGRP ligand, interfering with its ability to bind to the CGRP receptor and activate the migraine. It is dosed by a 240 mg subcutaneous autoinjector for the 1st month only, followed by a 120 mg once monthly injection thereafter. The higher initial loading dose allows for obtaining a rapid steady state concentration level in the blood compared to Aimovig and Ajovy. The dose can be administered to the abdomen, arm, buttocks, or thigh areas. There have been some reports of hypersensitivity reactions (rash, allergic reactions, itching) as well.

There is an Emgality coupon available on the company’s website in which most commercial insurance plans can get the medication for $0 per month for up to 12 months.

 

Vyepti (Eptinezumab)

Vyepti was the 4th and most recent of the CGRP mAbs to become available. It is made by Lundbeck and was FDA approved for migraine prevention 2/21/20. The antibody is produced in Pichia pastoris yeast cells by recombinant DNA technology. It targets the CGRP ligand, rather than the CGRP receptor. It binds very strongly to the CGRP ligand, interfering with its ability to bind to the CGRP receptor and activate the migraine. It comes in 100 mg and 300 mg doses and is dosed once quarterly (every 3 months) by a quick 30-minute infusion. The 100 mg dose is the recommended starting dose which can be titrated as needed to the higher dose later.

This is the only intravenous (IV) option available. Since it is administered IV, it is 100% bioavailable compared to the bioavailability of the other subcutaneous injections of 50-82%. It also reaches Cmax (maximum concentration) in about 30 minutes compared to 5-7 days of the other subcutaneous injections. Therefore, not surprisingly Vyepti showed treatment benefit in the first 7 days, often as early as 1 day post treatment, and showed continued effect through week 4, which is great since many patients on the once monthly self-injection CGRP mAbs often report a wearing off effect as they are approaching their next due injection.

This is certainly a good first line consideration, but also a good option for patients who do not like the thought of giving themselves a once monthly shot, have injection site reactions, or have failed the other CGRP mAbs options. Studies have shown some impressive highlights compared to other mAbs. In both the chronic and episodic migraine studies, almost 31% of patients had 75% or more reduction in migraine days in the 1st month alone. In the chronic migraine studies, about 27% of patients had a 75% or more reduction in migraine days over the first 3 months with 100 mg. After the 2nd dose (months 4-6), this increased to over 39% of patients! In the episodic migraine studies, over 22% of patients had a 75% or more reduction in migraine days over the first 3 months with 100 mg. After the 2nd dose (months 4-6), this increased to over 33.5% of patients.

There is a Vyepti coupon available on the company’s website in which most commercial insurance plans can get the medication for $5 per infusion every 3 months.

 

Data comparisons of the CGRP mAbs

The comprehensive table which follows compares all available data between the 4 CGRP mAbs, as I have compiled from a combination of published studies, scientific posters, and supplemental data provided from medical science liaisons from each company. I have highlighted some of the data throughout the table when it is a unique aspect or superior response in that category. All 4 CGRP mAbs have variable highlights that makes them stand out from the others in various categories, but overall they are all very effective options as a medication class. It is important to realize that the data compiled in the table should not be considered as a direct head to head comparison between the medications, and not all data points were looked at for each drug. For each CGRP mAb, there were variations and differences in many trial aspects such as the study designs, how responder rates were calculated, statistical analysis used, trial endpoints, some responses were based on open label portions of trials (in which patients typically report a higher response rate when they know they are receiving the drug and not placebo), varying definitions such as “headache of at least moderate severity”, what defined a “headache” or “migraine day”, preventive medications being used simultaneously, and baseline migraine frequencies included in the studies. The extent of reduction in migraine days can be influenced by the patient’s baseline migraine frequency in both the episodic and chronic migraine studies (high frequency vs lower frequency). For example, some studies included patients with a much higher baseline migraine frequency, and thus the extent of their migraine day reduction may not be as great as a group studied with a lower baseline frequency to start with.

  Aimovig (Erenumab) Ajovy (Fremanezumab) Emgality (Galcanezumab) Vyepti (Eptinezumab)
Dosing 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 1st month followed by 120 mg monthly 100 mg or 300 mg quarterly by 30-minute intravenous (IV) infusion
Target CGRP receptor CGRP ligand CGRP ligand CGRP ligand
Half-life 28 days 31 days 27 days 27 days
Median Peak Serum Concentration 6 days 5-7 days 5 days 30 minutes (after infusion)
Steady State 3 months 168 days (6 months) After the 240 mg loading dose After 1st dose
Bioavailability 82% 54-57% N/A 100%
Episodic migraine: Reduction in mean monthly migraine days in month 1 70 mg: -2.32 days

140 mg: -2.72 days Placebo: -0.9 days

675 mg quarterly: -3.3 days

225 mg monthly: -3.5 days

Placebo: -1.7 days

N/A N/A
Episodic migraine: Reduction in mean monthly migraine days in months 1-3 N/A 675 mg quarterly: -3.7 days

225 mg monthly: -3.4 days

Placebo: -2.2 days

 

*Months 1-3 in long term extension study (open label):

675 mg quarterly: -4.7 days

225 mg monthly: -4.8 days

120 mg monthly: -4.1 days

Placebo: -2.1 days

100 mg: -3.9 days

300 mg: -4.3 days

Placebo: -3.2 days

Episodic migraine: Reduction in mean monthly migraine days in months 4-6 70 mg: -3.2 +/- 0.2 days

140 mg: -3.7 +/- 0.2 days

Placebo: -1.8 +/- 0.2 days

N/A 120 mg monthly: -5 days

Placebo: -3 days

100 mg: -4.5 days

300 mg: -4.8 days

Placebo: -3.8 days

Episodic migraine: Reduction in mean monthly migraine days in months 1-6 N/A 675 mg quarterly: -5 days

225 mg monthly: -4.9 days

 

*months 1-3 placebo, months 4-6 open label

120 mg: -4.3-4.7 days

Placebo: -2.3-2.8 days

N/A
Episodic migraine: Reduction in mean monthly migraine days in months 1-12 70 mg: -4.22 +/- 0.22 days

140 mg: -4.64 +/- 0.19 days

Placebo: -1.8 days

675 mg quarterly: -5.2 days

225 mg monthly: -5.1 days

 

*months 1-3 placebo, months 4-12 open label

120 mg: -5.13 days

 

*12 month safety study with no placebo

100 mg: -4.6 days

300 mg: -5.2 days

Placebo: -4 days

 

*Reported as months 7-12

Episodic migraine:

50% or more reduction in migraine days in month 1

70 mg: 32.7%

140 mg: 35.5% Placebo: 15.5%

675 mg quarterly: 44%

225 mg monthly: 47% Placebo: 25%

 

120 mg: 50.8%

Placebo: 23.7%

100 mg: 59.3%

300 mg: 56.3%

Placebo: 40.5%

Episodic migraine:

50% or more reduction in migraine days in months 1-3

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%

Episodic migraine:

50% or more reduction in migraine days in months 4-6

70 mg: 43%

140 mg: 50%

Placebo: 26.6%

N/A 120 mg: 67%

Placebo: 43%

 

*At month 4 alone:

120 mg: 65.2%

Placebo: 41.9%

 

*At month 5 alone:

120 mg: 68.6%

Placebo: 43.7%

 

*At month 6 alone:

120 mg: 66%

Placebo: 44.8%

100 mg: 62%

300 mg: 65.3%

Placebo: 51.4%

Episodic migraine:

50% or more reduction in migraine days in months 1-6

N/A 675 mg quarterly: 65%

225 mg monthly: 60%

 

*months 1-3 placebo, months 4-6 open label, data is at month 6

120 mg: 59.3-62.3% days

Placebo: 36-38.6%

N/A
Episodic migraine:

50% or more reduction in migraine days in months 1-12

70 mg: 61%

140 mg: 64.9% Placebo: N/A

675 mg quarterly: 66%

225 mg monthly: 68%

 

*months 1-3 placebo, months 4-12 open label, data is at month 12

N/A 100 mg: 64.7%

300 mg: 69.4%

Placebo: 55.9%

 

*Reported as months 7-12

Episodic migraine:

75% or more reduction in migraine days in month 1

N/A 675 mg quarterly: 20%

225 mg monthly: 22% Placebo: 10%

 

120 mg: 25.7%

Placebo: 6.5%

 

100 mg: 30.8%

300 mg: 31.5%

Placebo: 20.3%

Episodic migraine:

75% or more reduction in migraine days in months 1-3

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%

Episodic migraine:

75% or more reduction in migraine days in months 4-6

70 mg: 20.8%

140 mg: 22%

Placebo: 7.9%

N/A 120 mg: 42%

Placebo: 24%

 

*At month 4 alone:

120 mg: 41.6%

Placebo: 15.2%

 

*At month 5 alone:

120 mg: 41.4%

Placebo: 15.5%

 

*At month 6 alone:

120 mg: 43.9%

Placebo: 15.8%

100 mg: 33.5%

300 mg: 40.1%

Placebo: 24.8%

Episodic migraine:

75% or more reduction in migraine days in months 1-6

N/A 675 mg quarterly: 39%

225 mg monthly: 37%

 

*months 1-3 placebo, months 4-6 open label, data is at month 6

120 mg: 33.5-38.8%

Placebo: 17.8%-19.3%

 

N/A
Episodic migraine:

75% or more reduction in migraine days in months 1-12

70 mg: 38.5%

140 mg: 40.8% Placebo: N/A

675 mg quarterly: 42%

225 mg monthly: 45%

 

*months 1-3 placebo, months 4-12 open label, data is at month 12

N/A 100 mg: 41.2%

300 mg: 47.7%

Placebo: 32%

 

*Reported as months 7-12

Episodic migraine:

100% reduction in migraine days in month 1

N/A 675 mg quarterly: 5%

225 mg monthly: 8% Placebo: 2%

 

120 mg: 8.8%

Placebo: 2.2%

 

100 mg: 8.6%

300 mg: 14.9%

Placebo: 5.9%

Episodic migraine:

100% reduction in migraine days in months 1-3

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%

Episodic migraine:

100% reduction in migraine days in months 4-6

70 mg: 3.2%

140 mg: 5%

Placebo: 2.8%

N/A 120 mg: 17%

Placebo: 9%

 

*At month 4 alone:

120 mg: 16.3%

Placebo: 8.5%

 

*At month 5 alone:

120 mg: 17.6%

Placebo: 8.7%

 

*At month 6 alone:

120 mg: 16.5%

Placebo: 9.5%

100 mg: 19.8%

300 mg: 24.5%

Placebo: 14.3%

Episodic migraine:

100% reduction in migraine days in months 1-6

N/A 675 mg quarterly: 18%

225 mg monthly: 20%

 

*months 1-3 placebo, months 4-6 open label, data is at month 6

120 mg: 11.5-15.6%

Placebo: 5.7-6.2%

 

N/A
Episodic migraine:

100% reduction in migraine days in months 1-12

70 mg: 19.8%

140 mg: 21.2% Placebo: N/A

675 mg quarterly: 17%

225 mg monthly: 21%

 

*months 1-3 placebo, months 4-12 open label, data is at month 12

N/A 100 mg: 26.8%

300 mg: 30.6%

Placebo: 20.5%

 

*Reported as months 7-12

Chronic migraine: Reduction in mean monthly migraine days in month 1 70 mg: -5 +/- 0.42 days

140 mg: -5.1 +/- 0.42 days

Placebo: -2.7 +/- 0.34 days

675 mg quarterly: -4.8 days

225 mg monthly: -4.7 days

Placebo: -2.7 days

120 mg: -4.06

Placebo: -1.78

 

N/A
Chronic migraine: Reduction in mean monthly migraine days in months 1-3 70 mg: -6.6 +/- 0.4 days

140 mg: -6.6 +/- 0.4 days

Placebo: -4.2 +/- 0.4 days

675 mg quarterly: -5 days

225 mg monthly: -4.9 days

Placebo: -3.2 days

 

*Months 1-3 in long term extension study (open label):

675 mg quarterly: -6 days

225 mg monthly: -6.7 days

120 mg: -4.8 days

Placebo -2.7 days

 

*At month 2 alone:

120 mg: -5.01

Placebo: -3.04

 

*At month 3 alone:

120 mg: -5.41

Placebo: -3.39

100 mg: -7.7 days

300 mg: -8.2 days

Placebo: -5.6 days

Chronic migraine: Reduction in mean monthly migraine days in months 4-6 N/A N/A N/A 100 mg: -8.2 days

300 mg: -8.8 days

Placebo: -6.2 days

Chronic migraine: Reduction in mean monthly migraine days in months 1-6 N/A 675 mg quarterly: -6.5 days

225 mg monthly: -7.6 days

 

*months 1-3 placebo, months 4-6 open label

N/A N/A
Chronic migraine: Reduction in mean monthly migraine days in months 1-12 70 mg: -8.5 days

140 mg: -10.5 days

Combined 70 mg and 140 mg: -9.3 days

Placebo: N/A

675 mg quarterly: -7.2 days

225 mg monthly: -8 days

 

*months 1-3 placebo, months 4-12 open label

120 mg: -7.21

 

*12 month safety study with no placebo

N/A
Chronic migraine:

50% or more reduction in migraine days in month 1

70 mg: 23.9%

140 mg: 28.3% Placebo: 11.4%

675 mg quarterly: 33%

225 mg monthly: 36%

Placebo: 19%

120 mg: 26.4%

Placebo 11%

 

100 mg: 54.5%

300 mg: 60.6%

Placebo: 36.1%

Chronic migraine:

50% or more reduction in migraine days in months 1-3

70 mg: 40%

140 mg: 41%

Placebo: 23%

675 mg quarterly: 30.7%

225 mg monthly: 33.3%

Placebo: 19.9%

 

*At month 3 alone (not averaged over months 1-3):

675 mg quarterly: 37%

225 mg monthly: 39% Placebo: 25%

 

*At month 3 in long term extension study (open label):

675 mg quarterly: 42%

225 mg monthly: 48%

120 mg: 27.6%

Placebo 15.4%

 

*At month 2 alone:

120 mg: 30.7%

Placebo: 17.7%

 

*At month 3 alone:

120 mg: 35.2%

Placebo: 24.7%

 

100 mg: 57.6%

300 mg: 61.4%

Placebo: 39.3%

Chronic migraine:

50% or more reduction in migraine days in months 4-6

N/A N/A N/A

 

 

100 mg: 61%

300 mg: 64%

Placebo: 44%

Chronic migraine:

50% or more reduction in migraine days in months 1-6

N/A 675 mg quarterly: 44%

225 mg monthly: 54%

 

*months 1-3 placebo, months 4-6 open label, data is at month 6

N/A, however:

 

*At month 6 in open label extension trial:

120 mg: 44.5%

N/A
Chronic migraine:

50% or more reduction in migraine days in months 1-12

70 mg: 53.3%

140 mg: 67.3%

Combined 70 mg and 140 mg: 59%

Placebo: N/A

675 mg quarterly: 53%

225 mg monthly: 57%

 

*months 1-3 placebo, months 4-12 open label, data is at month 12

N/A, however:

 

*At month 9 in open label extension trial:

120 mg: 53.9%

 

*At month 12 in open label extension trial:

120 mg: 56.9%

N/A
Chronic migraine:

75% or more reduction in migraine days in month 1

N/A Month 1 in long term extension study (open label):

675 mg quarterly: 21%

225 mg monthly: 21%

N/A 100 mg: 30.9%

300 mg: 36.9%

Placebo: 15.6%

Chronic migraine:

75% or more reduction in migraine days in months 1-3

70 mg: 17%

140 mg: 20.9% Placebo: 7.8%

675 mg quarterly: 9.6%

225 mg monthly: 12.3%

Placebo: 5.4%

 

*At month 3 in long term extension study (open label):

675 mg quarterly: 20%

225 mg monthly: 24%

120 mg: 7%

Placebo 4.5%

 

100 mg: 26.7%

300 mg: 33.1%

Placebo: 15%

Chronic migraine:

75% or more reduction in migraine days in months 4-6

N/A N/A N/A 100 mg: 39.3%

300 mg: 43.1%

Placebo: 23.8%

Chronic migraine:

75% or more reduction in migraine days in months 1-6

N/A 675 mg quarterly: 28%

225 mg monthly: 24%

 

*months 1-3 placebo, months 4-6 open label, data is at month 6

N/A, however:

 

*At month 6 in open label extension trial:

120 mg: 21.7%

N/A
Chronic migraine:

75% or more reduction in migraine days in months 1-12

70 mg: 27.1%

140 mg: 41.8%

Combined 70 mg and 140 mg: 33.2%

Placebo: N/A

675 mg quarterly: 28%

225 mg monthly: 31%

 

*months 1-3 placebo, months 4-12 open label, data is at month 12

N/A, however:

 

*At month 9 in open label extension trial:

120 mg: 27.9%

 

*At month 12 in open label extension trial:

120 mg: 31.1%

N/A
Chronic migraine:

100% reduction in migraine days in month 1

N/A Month 1 in long term extension study (open label):

675 mg quarterly: 6%

225 mg monthly: 5%

N/A 100 mg: 7.9%

300 mg: 13.4%

Placebo: 2.7%

Chronic migraine:

100% reduction in migraine days in months 1-3

70 mg: 4.3%

140 mg: 2.7%

Placebo: 0.4%

675 mg quarterly: 5.3%

225 mg monthly: 4.5%

Placebo: 4%

 

*At month 3 in long term extension study (open label):

675 mg quarterly: 5%

225 mg monthly: 6%

120 mg: 0.7%

Placebo 0.5%

 

100 mg: 10.8%

300 mg: 15.1%

Placebo: 5.1%

Chronic migraine:

100% reduction in migraine days in months 4-6

N/A N/A N/A 100 mg: 17.8%

300 mg: 20.8%

Placebo: 9.3%

Chronic migraine:

100% reduction in migraine days in months 1-6

N/A 675 mg quarterly: 8%

225 mg monthly: 8%

 

*months 1-3 placebo, months 4-6 open label, data is at month 6

N/A N/A
Chronic migraine:

100% reduction in migraine days in months 1-12

70 mg: 6.1%

140 mg: 12.7%

Combined 70 mg and 140 mg: 8.9%

Placebo: N/A

675 mg quarterly: 9%

225 mg monthly: 10%

 

*months 1-3 placebo, months 4-12 open label, data is at month 12

N/A N/A
Side effects:

Nasopharyngitis

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

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

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:

Cramps, muscle spasms

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

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



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