CGRP for migraine: acute treatment and prevention

Introduction to CGRP for migraine

There are two types of CGRP drug groups that are available – monoclonal antibodies and CGRP receptor antagonists (gepants). These groups represent a newer class of migraine-specific medications that are used to treat and prevent migraines. I will not be covering any monoclonal antibodies medications in today’s article. 

In this post, I will focus on information about CGRP for migraine in the form of CGRP receptor antagonists (gepants). In 35 years of my migraine journey, I found the gepants to be most effective in the treatment of my own acute migraines. During the recent Migraine World Summit, CGRP for migraine was discussed as the biggest breakthrough in the migraine treatment field in a long time.

Note: I am not a healthcare provider, thus this information is meant for general awareness and education about available options. You need to consult with your doctor about any of these medications. I am also not an affiliate of any kind with any of the pharmaceutical companies that produce migraine medications. I was not paid to produce this post.

CGRP for migraine – Mechanism of action

Gepants are small molecule drugs designed to specifically block the CGRP (calcitonin gene-related peptide) protein. This protein is believed to play a significant role in the development of migraine pain and inflammation during a migraine attack.

CGRP levels are higher during the migraine attack. These proteins are bombarding the sensory nerve endings causing migraine symptoms we are all too familiar with! CGRP receptor antagonists (gepants) block these proteins from attaching to the nerve endings, thus relieving pain, light & sound sensitivity, and nausea.

CGRP for migraine – the solution for acute and preventative treatment   

When I first tried a gepant to treat one of my acute migraine attacks, I was pleasantly surprised. Minimal side effects and no risk of rebound made it an exciting breakthrough for me as a patient. Little did I know at the time that CGRP blockers or gepants were considered a major breakthrough in migraine medicine in a long time. But this was just the beginning!

Another cosmic shift in the migraine treatment landscape happened with approval for some of these gepants to be used not only for acute migraine treatment but also for migraine prevention. For example, clinical trials conducted for one of the gepants called Nurtec ODT showed that the more the patients took Nurtec the less headaches they had. That is how the idea of preventative use was derived. This is also the opposite of developing a medication overuse headache.

Many advocacy organizations and medical communities are currently discussing the addition of several fantastic options for both – migraine prevention and acute migraine treatment – thanks to the invention of CGRP blockers (gepants).  

Table: CGRP for migraine – approved indications  

CGRP for migraine: acute treatment

Let’s review in more detail the three gepants that have been approved for acute migraine treatment.

Ubrelvy tablets

Ubrelvy (ubrogepant) is a prescription medicine that is used to treat acute migraine with or without aura in adults. Here is some important information about it directly from the Ubrelvy website:

• In clinical studies, the majority of patients achieved pain relief, and 1 in 5 even experienced total pain freedom.
• Plus, 2 out of 5 had the absence of their most debilitating symptom within 2 hours after taking UBRELVY.

Ubrelvy pills come in 50mg and 100mg doses. I tried a 50mg dose and eventually went to use a 100mg dose as it was more effective.

My reasons for trying Ubrelvy.

Too many migraine pain days a month.

I have chronic migraines which means I have more than 15 days of migraine symptoms a month. In my case, I experience migraine symptoms between 20 and 25 days a month. It represents a unique challenge because most acute abortive medications have a limit as to how frequently they can be used. If they are used too frequently, they will stop helping or can cause medication overuse headaches.

Only one effective abortive medication so far.

After trying many abortive meds that were ineffective or only partially effective, my doctor prescribed Relpax (eletriptan), a triptan group of medications, as an abortive medication. Relpax has been very effective in treating acute attacks for me. But it can only be used a few times a month (8-9 times). It also gave me some side effects like muscle fatigue, tiredness, and aching joints. I could tolerate it well though for the most part and it became a reliable acute migraine medication for me.

Advil and other over-the-counter medications are completely ineffective in treating my acute symptoms. I tried using other abortive meds like ergo group, but they were ineffective or caused many intolerable side effects for me. So, I was on the lookout for any additional abortive medication that I could use and avoid Relpax overuse. Rebound headache is no fun! So, I knew that overusing any acute med is a no-go for me. 

When I heard that Ubrelvy was introduced, I did some research and talked to my doctor about it. We decided to give it a try.

Here is my experience with Ubrelvy:

The first time I took Ubrelvy, I was nervous and hopeful at the same time. I prayed for it to be effective and to help me. Nothing happened for the first hour or so, and I started to feel that sad feeling of disappointment building in my chest. But I pushed it away and kept waiting. Then it felt as if someone just waved a wand and my pain started to subside, all the nausea and sound/light/smell sensitivity was gone. I looked to see how long it took – 1 hour 45 minutes.

Summary of experience with Ubrelvy:

• I take 100mg pill and it usually works within 2 hours to take care of the pain and all the migraine symptoms.
• Convenient packets that are easy to open. If you have ever tried to open some hard-to-open meds while in migraine agony, you will appreciate how easy this one is to open!
• Unlike other medications, it doesn’t make me feel tired or lethargic.
• The second dose can be taken within 2 hours if the first one didn’t help. I only had to do it a couple of times though. In 1.5 years of taking Ubrelvy, one dose reliably helps me most of the time.
• With 8 days of Relpax and 8 days of Ubrelvy use, I can get coverage for many of my migraine attack days.
• My doctor checks my blood counts once in a while just to make sure everything is ok. Tell to your doctor, if you have known liver or kidney problems, pregnant or breastfeeding, because Ubrelvy may not be for you in that case.
• My insurance covered Ubrelvy and I have very little co-pay. If your insurance doesn’t cover it, there are various programs available to reduce costs.

Overall, my experience with Ubrelvy has been very positive. I now use Ubrelvy as my first line of defense and take Relpax on other days.

Nurtec ODT for acute migraine treatment 

Nurtec ODT (Rimegepant) is an orally disintegrating tablet used for the acute treatment of migraine attacks in adults. It is approved by the FDA for acute migraine treatment as well as migraine prevention. Here I will outline some information about migraine treatment. For prevention, read further below.

Like other CGRP for migraine, Nurtec ODT works by blocking the activity of CGRP, a protein associated with migraine attacks, thereby reducing inflammation and pain signals in the brain.

What is interesting about this medication is that it provides relief from acute migraines by rapidly dissolving on the tongue and being quickly absorbed into the bloodstream for effective and convenient treatment. I didn’t find any other CGRP medications in a dissolving tablet form.

The typical recommended dosage for Nurtec ODT in the treatment of acute migraines is a single dose of 75 mg, which can be taken once every 24 hours as needed for migraine relief.

Here are some data points from the pivotal clinical trials on this medication:

• Nurtec ODT was found to effectively relieve migraine pain within 2 hours in clinical trials.
• It provided sustained pain relief for up to 24 and 48 hours after taking the medication.
• Patients experienced a significant reduction in pain intensity as early as 15 minutes after taking Nurtec ODT.

I have not personally taken Nurtec ODT for acute migraine since I have been taking Ubrelvy which has been effective for my attacks. You need to consult with your doctor as to which of these gepants is best for you to treat acute episodes.

Zavzpret (zavegepant) nasal spray CGRP for acute migraine treatment

Pfizer, who makes Qulipta (atogepant), recently (May 2023) received FDA approval for a nasal spray gepant called Zavzpret (zavegepant).

Zavzpret nasal spray is indicated for the acute treatment of migraine with or without aura in adults. It comes in a single dose of 10mg, administered into one nostril. That is also the maximum daily dose according to the full prescribing information for this medication. Zavzpret safety was not evaluated for treating more than 8 migraines in a 30-day period.  

Potential reasons to consider Zavzpret for acute migraine treatment:

If you have vomiting and nausea accompanying your migraine attack, this might be worth discussing with your doctor, since the nasal spray mechanism of action does not involve swallowing a pill in the midst of a bout of vomiting.

Also, Zavzpret may be an interesting option for a faster-acting therapy. Here is the information I took from Pfizer press release about FDA approval for this drug:

“In its pivotal Phase 3 study, ZAVZPRET was statistically superior to placebo on the co-primary endpoints of pain freedom and freedom from most bothersome symptom at two hours post-dose. The pivotal study also demonstrated pain relief as early as 15 minutes in a prespecified secondary endpoint versus placebo.”

From my research, it looks like Zavzpret is not yet available in pharmacies because it was just approved. So, it will be interesting to see when it will become commercially available to patients and how insurance companies will approach its coverage. But it is exciting to see this new form of CGRP receptor antagonists to be added into the tool box of our treatment options for migraine.

CRP for migraine prevention: the new frontier of migraine treatments

Nurtec ODT every other day for migraine prevention

This is truly exciting because it is the only migraine treatment that is FDA-approved for both – acute and preventive therapy of certain migraines.

In my recent post about innovative migraine treatments that were discussed at the 2023 Migraine World Summit, I mentioned a session by Dr. Tepper. He talked about how blocking the receptor every day or every other day will produce a preventative effect. After the studies for acute migraine treatment with Nurtec ODT were complete, the company performed a series of studies to evaluate Nurtec taken every other day for the prevention of migraine.

The subsequent published study included episodic and chronic patients who took it every other day for prevention. The results were great and the FDA then approved it for episodic migraine prevention. For those who have less than 15 migraines per month.

Here is the main result from the clinical trial that studied Nurtec for migraine prevention:

• Nurtec ODT decreased monthly migraine days by 4.3 days/month after 3 months of treatment in adult patients with episodic migraine.

In addition, the newly approved product label allows the use of Nurtec ODT up to 18 doses per month for both acute and preventive therapy, regardless of the number of monthly migraine days.

Daily Qulipta for migraine prevention

You now have even more options for migraine prevention without worrying about medication overuse headaches. QULIPTA is a prescription medicine used for the preventive treatment of migraine in adults.

Qulipta (Atogepant) is a daily gepant that was originally FDA-approved for the prevention of episodic migraine, i.e. less than 15 migraine days a month. Recently Qulipta was also FDA-approved for the prevention of any migraines, including chronic ones.

According to the launch release, Qulipta for episodic migraine prevention is available in three strengths  – 10 mg, 30 mg, and 60 mg. Only the 60 mg dose of Qulipta is indicated for the preventive treatment of chronic migraine.

Here are some data points from Qulipta clinical trials:

• The trial studying Qulipta for episodic migraines showed that the majority of patients achieved a 50% to 100% reduction in monthly migraine days
• The trial studying Qulipta for chronic migraines had patients who had high frequency (average of 19 migraine days per month) and severe disability (more than 15 acute medication uses per month). The results show that on average, patients got nearly 1 week’s worth of migraine-free days back in their lives per month.
• The trial studying the functional impact of Qulipta showed improvement in function related to daily social & work-related activities for patients who took Qulipta versus placebo.

The overall safety profile of QULIPTA is consistent with the episodic migraine patient population, with the most common adverse events including constipation, nausea, and fatigue/sleepiness.

Essentially, Qulipta is the only gepant that has been approved for the prevention of chronic migraines and migraines of any frequency! Nurtec ODT is only approved for the prevention of episodic migraines.

I recently discussed Qulipta with my physician and made a decision to try it. I will need to stop taking Ubrelvy and only take Qulipta. Once my insurance sorts out the coverage, I can try this new preventative treatment and be sure to write about it.

Safety and side effects of CGRP Inhibitors

The most common side effects of gepants are nausea, dry mouth, fatigue, and dizziness. The general safety profile is promising compared to many other migraine-related medications. But there are a couple of nuances to be mindful about:

Check your liver counts in the first few months of using them.

Gepants are small-molecule drugs that block the CGRP receptor and are effective at both relieving migraines and preventing them. Unlike monoclonal antibodies, gepants rapidly penetrate the brain which means they work quickly.  However, they are metabolized in the liver so there is a higher potential for interactions and possibly liver damage.

My doctor ordered a blood test at 30 days after using Ubrelvy and then at 90. My liver enzymes were normal and not elevated, so I then continued to use my medication.

I collaborate with both of my physicians – my primary care provider and my neurologist – on my care. So, whenever I do any wellness checks, I remind my primary care doctor to check my liver function. You need to be proactive in your advocacy. 

Only one gepant can be taken.

My doctor told me that once I start taking daily Qulipta, I will need to stop taking Ubrelvy (my acute migraine med) to ensure safety. You will need to discuss with your doctor which other abortive medication you could take instead if you decide to use Qulipta for prevention. For example, I will take Relpax.  

Conclusion

With all of these new options of CGRP for migraine, patients like you and I can use gepants to treat acute attacks or prevent migraines. With a promising safety profile in terms of side effects and tolerability, gepants can be an interesting option for migraine management.

The key is to discuss with your doctor what your migraine frequency and severity is and which of these options makes the most sense for you to try.