Which is the best CGRP monoclonal antibody (mAb) receptor antagonist for migraine prevention?
Emgality vs. Ajovy, Ajovy vs. Vyepti, Aimovig vs. Ajovy, Aimovig vs. Emgality, Aimovig vs. Vyepti, Emgality vs. Vyepti. Which of them is best? This is a common question I get asked in the headache clinic all the time.
The answer is that they are all very effective with good data supporting their benefit in clinical studies in both episodic and chronic migraine. However, there are highlights of each CGRP mAb that separate them from each other. These differences can help you decide which may be the best one for you to try first.
It’s also important to know that failure to one of them (or multiple) does not necessarily predict failure to all of them.
This blog article will discuss and compare the 4 CGRP monoclonal antibody (CGRP mAb) migraine preventive treatments including Aimovig (Erenumab), Ajovy (Fremanezumab), Emgality (Galcanezumab), and Vyepti (Eptinezumab). Hopefully it will help you and your doctor choose which one may be best for you.
Background of the CGRP mAbs
The CGRP (calcitonin gene related peptide) monoclonal antibody (mAb) receptor antagonists (from now on we’ll call them the CGRP mAbs) were the 1st migraine specific preventive medications that were FINALLY developed purely for migraine prevention. The first (Aimovig) came to market in Spring of 2018 and the other 3 (Emgality, Ajovy, Vyepti) followed shortly after.
This was a major step forward for migraine management because prior to 2018, all of the migraine preventive medication options we’ve always used had been “adopted” from other specialties.
For example, the 3 main categories of preventive migraine medicines prior to 2018 were select evidence-based options within the anticonvulsant (anti-seizure), anti-depressant/anti-anxiety, and anti-hypertensive (blood pressure) medicine categories. None of them were created specifically for migraine, but overtime some were found to be helpful in migraine prevention.
These conventional migraine preventive treatments are still used, can certainly be effective for some, and are discussed in much greater detail here. Unfortunately, there are still many migraine patients that do not respond to these older options, or they have side effects with them.
What is Calcitonin Gene Related Peptide (CGRP), and how does CGRP relate to migraine?
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) which triggers more CGRP release and pain. It increases pain transmission and is a very potent inflammatory protein. Basically, CGRP intensifies migraine pain and plays a role in triggering a migraine.
CGRP has been studied since the early 1980s. It was discovered throughout the trigeminovascular system (the “on switch” for migraine), which is the trigeminal nerve network that forms the basis for all pain transmission throughout the head and face. So naturally, a role in migraine was suspected.
In the early 1990s it was shown that CGRP was released by the trigeminal nerves and levels increased in the blood 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 decreased 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 (Aimovig, Emgality, Ajovy), and a 4th CGRP mAb FDA approved in 2020 (Vyepti).
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) antibody by a process called recombinant DNA technology.
The non-human part of the antibody binds to the target (either the CGRP ligand (protein) or CGRP receptor), and the human part makes it less likely to be seen as a “foreign antigen” by our body so it won’t be destroyed by our immune system.
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).
To review, antibodies are proteins made by living organism cells which bind unique parts of proteins recognized as “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 it 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. Similarly, the CGRP mAbs are made to bind either the CGRP protein itself, or the receptor where the CGRP binds (the migraine “on” switch).
How do the CGRP mAbs work for migraine?
The CGRP mAbs target either the CGRP receptor and block it (antagonist) to prevent the CGRP protein from binding it, or they target the CGRP protein itself and prevent it from binding (sticking) to the CGRP receptor. The result of either of these actions is that the migraine is prevented from starting, or becomes much less frequent and severe if it does still occur periodically.
How effective are the CGRP mAbs in migraine prevention?
The CGRP mAbs tend to all be quite effective in general. All of them have been proven to be very effective for both episodic migraine (14 or less headache days per month) and chronic migraine (15 or more headache days per month).
In the majority of CGRP mAb studies, 50% or more of patients had a reduction of 50% or more migraine days per month. In other words, more than half of all patients cut their monthly migraines by half or more. Studies also showed that about 1/3rd of patients were “super responders”, decreasing their monthly migraine frequency by 75% or more. Some patients even received 100% migraine reduction (yes, that means 0 migraines). For example, in the Vyepti study (PROMISE-2) looking specifically at chronic migraine improvement (patients averaged 15-26 headache days per month), almost 21% had 100% monthly migraine day reduction after the 2nd quarterly dose of 300 mg.
Some may respond better to the CGRP receptor blockade type, whereas others may do better with the CGRP protein binding type. So if one 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 very well to another. I’ve seen people that failed 3 of them, but then did really well with the 4th one they tried. I’ve seen this a number of times with Vyepti, for example.
So, if you do not respond to one type of CGRP mAb target (such as the CGRP receptor), it may be worth trying the other type of CGRP mAb target (such as the CGRP protein).
The CGRP mAbs are administered by injection (easy push button auto-injection shot or syringe if you prefer) or IV infusion. Oral absorption is poor and degradation in the gastrointestinal system would inactivate the antibodies before they would even be able to enter the blood. They are absorbed by the lymphatic system and into the blood. Metabolism occurs in the reticuloendothelial system, not the liver or kidneys.
How fast do the CGRP mAbs work?
Compared to historical oral migraine preventive medicines, the CGRP mAbs often work faster and do not require a slow dose titration, as is done with oral preventives.
CGRP mAbs are sometimes seen to be effective in just a few days, and often within a month. The general recommendation is a trial of at least 3 months, and if receiving some benefit at that point, another 3 months is suggested for further improvement to be seen. The data suggests that the longer a patient is on a CGRP mAb, the more effective it is and the further the migraine reduction. However, there is a phenomenon that we sometimes see where a patient starts to wear off after a year or more of use, but this is not seen in the majority of patients.
What are the most common CGRP mAb side effects?
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 historically use. The most common side effects are mild injection site reactions, injection site tenderness, and nasopharyngitis (although risk is low and typically mild). More specific side effects reported with each individual CGRP mAb are discussed further below and can be seen in the table below.
Cumulative data show no immunological (they do not suppress or alter the immune system), cardiovascular, or neurological safety concerns of significance.
What are the differences between the CGRP mAbs?
The 4 different CGRP mAbs are each detailed and compared below in order of FDA approval. 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 unique in that it is the only one that targets the CGRP receptor rather than the CGRP protein itself. Therefore, it binds to the receptor, blocking the ability of the CGRP ligand to bind to the receptor and activate the migraine.
How is Aimovig Dosed?
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.
What are the side effects of Aimovig?
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 (similar to all the other CGRP mAbs), and up to 1 week after. Nasopharyngitis was also a reported side effect in some patients (similar to all the others).
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). Vyepti and Ajovy have the least risk of constipation, and it is also rare with Emgality.
Post-marketing observations have suggested some worsening of pre-existing hypertension, although this has more recently been debated. 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 copay card on the company’s website in which most commercial insurance plans can get the medication for as low as $5 per month.
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 protein, rather than the CGRP receptor. By binding to the CGRP protein, it blocks the protein’s ability to bind to the CGRP receptor and activate the migraine.
How is Ajovy dosed?
Ajovy 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.
What are the side effects of Ajovy?
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. Nasopharyngitis was also a reported side effect in some patients.
Ajovy has the least potential for constipation (along with Vyepti), 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 of the self injection CGRP mAbs (31 days compared to 27-28 days), meaning it lasts the longest. So it’s the self-injection CGRP mAb (monthly or quarterly dose) to consider switching to if your Aimovig or Emgality tends to wear off a week or more early before the next dose is due.
There is an Ajovy copay card available on the company’s website in which most commercial insurance plans can get the medication for as low as $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 protein, rather than the CGRP receptor. Thus, it binds to the CGRP protein, interfering with the protein’s ability to bind to the CGRP receptor and activate the migraine.
How is Emgality dosed?
It is dosed by a 240 mg subcutaneous autoinjector (or syringe) 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. So it reaches a therapeutic level in the blood quicker. The dose can be administered to the abdomen, arm, buttocks, or thigh areas.
What are the side effects of Emgality?
There have been some reports of hypersensitivity reactions (rash, allergic reactions, itching) as with all of the self-injection CGRP mAbs. Nasopharyngitis was also a reported side effect in some patients, similar to the other CGRP mAbs.
There is an Emgality copay card available on the company’s website in which most commercial insurance plans can get the medication for as low as $0 per month.
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 protein, rather than the CGRP receptor. It binds very strongly to the CGRP protein (much stronger than the other CGRP mAbs), interfering with its ability to bind to the CGRP receptor and activate the migraine. Because it binds so tightly and precisely to the CGRP protein, it has the longest half life and lasts the longest. This is why it is only dosed 4 times per year (every 3 months).
How is Vyepti dosed?
Vyepti 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 as needed.
Vyepti 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%. In other words, it can start working immediately. It reaches 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, as early as 1 day post treatment. This 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. So if you wear off a week or so early with the once monthly self-injection CGRP mAbs, Vyepti would be the best one to consider since it lasts the longest.
Vyepti is certainly a good first line consideration, but also a good option for patients who do not like giving themselves a once monthly shot, have injection site reactions, or have failed the other CGRP mAbs options.
Studies have shown impressive highlights compared to other CGRP mAbs in both the chronic and episodic migraine studies. In the chronic migraine studies (baseline migraine frequency 15-26 days per month), more than 33% of patients had a 75% or more reduction in migraine days with the 1st 300 mg dose. After the 2nd dose, this increased to more than 43% of patients receiving a 75% or greater reduction in monthly migraine days per month. Furthermore, after the 2nd dose 21% of patients received a 100% reduction in monthly migraine days per month (yes, that’s 0 migraines).
What are the side effects of Vyepti?
There have been some reports of hypersensitivity reactions (rash, allergic reactions, itching). Nasopharyngitis was also a reported side effect in some patients, similar to the other CGRP mAbs as well.
There is a Vyepti coupon available on the company’s website in which most commercial insurance plans can get the medication for as low as $0 per infusion treatment.
Data comparisons of the CGRP mAbs
The comprehensive table at the bottom of this blog compares 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.
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. Some studies were done with different designs and study end points. The table at the bottom will be periodically updated, so keep an eye out.
Are CGRP mAbs safe in pregnancy and breastfeeding?
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 use a CGRP mAb with Covid-19 or other vaccines?
There is no current evidence for an interaction between the Covid-19 or other vaccines and CGRP mAbs. 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 or other vaccination, nor do they need to be delayed or timed any differently in relation to receiving vaccination. Most physicians feel that there should theoretically be no interaction or contraindication to receiving either of these treatments in relation to vaccination because they are entirely different proteins with different mechanisms of action.
Can I use a CGRP mAb with Botox injections?
Botox and CGRP mAbs can be safely used together. In fact, there is evidence that using Botox with the CGRP mAbs works better together than with either individually due to synergistic effect. One study 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 with the gepants (Nurtec, Ubrelvy, Qulipta, Zavspret)?
The abortive gepant medications (Nurtec, Ubrelvy, Zavzpret), work by blocking the CGRP receptor (CGRP receptor antagonists). Nurtec is unique in that it is dually approved as a migraine abortive and/or migraine preventive. Qulipta is approved only as a migraine preventive.
The gepants are of a completely different molecule and design than the CGRP mAbs. The gepants can be safely used with the CGRP mAbs, and this is common practice.
In fact, there was a publication showing that when patients using Nurtec as an abortive had added Aimovig once monthly injection as a preventive treatment, they began consistently receiving 100% relief for their acute migraine attacks when they used their Nurtec. So, the combination of using Nurtec abortively in addition to using Aimovig preventively led to an even more effective acute migraine response.
There was a larger safety study publication which evaluated the acute treatment of migraine with Nurtec while using a CGRP mAb for migraine prevention. The CGRP mAbs used were Aimovig (7 patients), Ajovy (4 patients), and Emgality (2 patients). The study determined that Nurtec 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 of negative interactions 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 beyond the scope of this blog, the gepants (Nurtec, Qulipta) and the CGRP mAbs (Aimovig, Ajovy, Emgality, Vyepti) are compared to each other in more detail here in terms of migraine prevention benefits, and which may be better between them.
Conclusions
All 4 CGRP mAbs have variable highlights that makes them stand out from one another in various ways as discussed above. These differences can help to personalize which one to consider trying first. However, overall they are all very effective options as a preventive migraine medication class.
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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