- Weekly Updates
- Week 1 Update (Written on Friday, July 6, 2018, on Facebook)
- Week 2 Update (Written on Friday, July 13, 2018)
- Week 3 Update (as of Thursday, July 19, 2018)
- Week 4 Update (as of Thursday, July 26, 2018)
- Migraine Log
- Migraine Stats
- Articles Where “Aimovig” Appears:
- Aimovig: Community Feedback & Experiences
- So far little to no change
- Side effects from Aimovig
- Let’s keep the conversation going
- Do The New CGRP Drugs Work For Migraine?
- New Migraine Drug Approved: Four Things Health Execs Need to Know
- Salt and Health
- Medicinal Migraine Treatments
- Aimovig™—The Label
- Aimovig™— The Efficacy
- Aimovig™ Or Salt?
- We Need Your Help
How Aimovig Is Working For My Migraine: A Weekly Update (Month 1)
Originally Published: July 14, 2018 at 9:00 pm EST
If you follow me on social media, you know that I am now taking the Aimovig injection every month for Migraine prevention, as prescribed by my doctor. On this post, you will be able to keep up with my progress from week to week. The good, the bad, and the ugly. In the comments, let me know if you find any discrepancies. I am a person with Migraine, after all. I am both the writer and the editor, NOT a good combination!
Disclaimer: I was a paid Amgen and Novartis Spokesperson. This content reflects my own personal opinions and was not created or reviewed by Amgen and Novartis. I was not paid to write this article.
In case you prefer to jump around:
- Weekly Updates Intro
- Month 1
- Week 1
- Week 2
- Week 3
- Week 4
- Migraine Log
- Migraine Stats
- Go To Month 2 ⇗
- Go To Month 3 ⇗
Updates are in chronological order, from one week after the shot until the Written Date next to each entry. To see the data behind all of this, see the Migraine Log and Migraine Stats further down. For the sake of these stats, a Month is 28 days starting with injection #1. Let’s go!
Date of 1st Injection: Thursday, June 28, 2018
Time of Injection: 7:00 pm
Dosage: 140 mg (2 – 70mg Injection Pens)
Injection Site: Left Upper Leg
Date of 2nd Injection: Thursday, July 26, 2018
Time of Injection: 8:30 pm
Dosage: 140 mg (2 – 70mg Injection Pens)
Injection Site: Left Upper Leg
Week 1 Update (Written on Friday, July 6, 2018, on Facebook)
I took my first injection of Aimovig for chronic migraine last Thursday. While I’ve still had migraine attacks I’ve noticed that the severity has lessened a bit and I am more active. I am tired all the time, but that started before the shots. My insomnia did go away. I’ve slept all night every night since a couple days after the shot. It’s very early to have real answers about how well Aimovig will work for me, but after only a week, I have a really good feeling about it.
Week 2 Update (Written on Friday, July 13, 2018)
I use Migraine Buddy to track migraine attacks. Before my first injection, I was plagued with migraine attacks almost every day with pain levels rarely below 6. Keep in mind, there are a few days in early June where I didn’t notate my attacks out of laziness or just not feeling well. I didn’t go back to add them, but I have been tracking pretty close to 100%, definitely since the injection two weeks ago. Even so, you will notice a difference in pain level severity after the injection compared to before my first injection. See the section “To Compare” in the chart below.
Also, keep in mind, I’ve been going through Cognitive Behavioral Therapy (CBT) since December 2017. I’ve been able to cut down on a small portion of my depressive/stress triggers. Which is another reason you see a slight drop in migraine attacks after April 2018. The program works for you if you work hard for the program. Unfortunately, I did not see a decrease in pain severity like I have with Aimovig. Side note: I highly suggest CBT to help cut down on attacks by reducing triggers.
Photo Credit: Migraine.ie
If you don’t know what a trigger threshold is, read more about it here. Now that you’re educated about it, I have noticed a change in how my body reacts to some triggers. As time goes by I’m sure I’ll start to notice more and more changes, but for now, I realize I am not triggered as easily by cleaning. I mean light cleaning, like washing a couple dishes and sweeping a small area. Usually, this would set me off if my trigger threshold was low. I’m no doctor or scientist, so I couldn’t say if the medication helped increase a patient’s threshold, but that would be interesting to find out.
During this second week, post-injection, I have not had any side effects. I did have constipation that first week, but it slowly decreased as the days went by. I can happily say that right now, no side effects. Party over here!!
Boy, I have so much more energy than I did before the shot. Just ask my kids and the hubby! Ha! They secretly hate it, I know they do!!! Example, on Monday (7/9/18) I grabbed my teens and we (I mean they) swept the WHOLE house (we have wood floors), mopped the whole house (again, wood floors), cleaned up Sunday’s dishes (cause we’re not perfect), transferred about moving boxes into the outside storage building, and cleaned their rooms. You see, while I did help here and there and wear myself out, I actually had the energy to delegate all of this. I had the energy to ensure it was done right, which is my way, 😉 of course. I had the energy to be around them while they did all of this and talk to them while we worked. I know a lot of people take that for granted, but for me, that little time spent cleaning with my kids…it’s priceless. I hope for more days like that, though, I doubt they do!
I have Irritable Bowel Syndrome (IBS) that occurs only during migraine attacks. Yesterday, during a conversation with another person with Hemiplegic Migraine on Facebook, we discussed IBS and migraine. It occurred to me that I have not had IBS with any of my attacks since the shot. This is something I’ll be keeping an eye on for now. Do you get IBS only with migraine?
Week 2 Wrap-Up
It is my hypothesis that with all the events I have in play, like the CBT, to cut down on triggers together with Aimovig, I will not only continue to see a decrease in pain level severity but also in the number of attack days. Keep posted here every week to see an update of how it’s going!!
Week 3 Update (as of Thursday, July 19, 2018)
This week has a lot more reading than the previous two weeks. I had a doozy of a migraine attack but also some amazing revelations. So please don’t give up on me, I apologize ahead of time for a long read! It’s worth it, though, I promise!
If you don’t know what a trigger threshold is, read more about it here. Now, I have the same results here as last week. I am able to do more, push myself harder than I could before Aimovig. I’m not triggered so easily. Not to say that I’m not triggered by activity, because I still am, but it’s taking longer. And yes, I have pushed myself too hard, more than what I’m used to, and had a migraine attack.
Here’s a specific example, on the 19th I got up early with the husband and made him breakfast and packed him a sandwich for lunch. Then I immediately started cleaning the kitchen when he left for work. I was able to get through the small load in the sink and wipe down all the counters pretty successfully with no issue. I then decided I needed to do some light washing, we needed clean towels. So I got that done. So far so good!
I did feel a little winded so I thought it better to relax for a few hours. But relax to me means getting on my blog and writing. So on Thursday, I wrote 3 Ways You Can Find Your Diagnosis Codes. I did a lot of research that day after writing a mini-guide to the ICHD-3 and ICD-10 mentioned in the article for my new Migraine Support Group on Facebook. Needless to say, I spent HOURS on my computer that day. Sometimes just typing irritates the muscles in my left arm and sets off my Carpal Tunnel. To top it off, the Carpal Tunnel pain will trigger a Hemiplegic Migraine.
That evening, my sister invited us to walk over to her house for burgers. The kids decided to swim in the backyard, so we made an evening of it all. It was nice, the North Carolina weather was cooperating and we had a good time. It was just my kids and me, Stephen was catching up on sleep. He’s had a rough few days sleeping. At some point in the evening, I began to feel my sixth sense kick in. I call that weird, warning feeling I get right before an attack my sixth sense. As I was walking to go back into the house from outside in the backyard, I began to feel my left side stiffen. With Hemiplegic Migraine, one side of the body can become weak or paralyzed.
Seconds before that, though, I felt my sixth sense kick in. I knew. Weirdly, the weakness and stiffness only lasted a few seconds. By the time I reached the back door, which was about 4 feet away, I was back to normal. But because I get pretty cautious when I get this way, I took it relatively easy the rest of the night. I just didn’t feel normal, even though I looked and acted normal to everyone else. Nobody had any idea what I was going through. I didn’t want to alarm my kids just yet because it happened so fast and was gone just as quickly. The only lingering effect was a slight “off” feeling. But I get those all the time randomly throughout the day. Nobody ever knows.
After getting my fill of hamburgers and an amazing Smore’ we made on the fire outside, we all headed in to watch the ESPY awards my nephew recorded. They are BIG baseball fanatics and follow most of the sports on TV. They are both very talented and we just might see them on TV watching the ESPYs 😉 I had been sitting in an awkward position for maybe an hour. I wasn’t comfortable and I had started to feel my neck stiffen. I decided to lie down, but I think the damage had already been done. After an hour and a half of ESPY watching, I decided it was time to walk back home. So I sat up and immediately knew something was very wrong.
My sixth sense was on high alert and within seconds I had a full-blown, Level 9, Hemiplegic Migraine attack. With this attack I had severe pain (but not high enough to trigger seizures), transient aphasia, hemiparesis (weak on the left side of my body to include arm, hand, leg, foot) that caused me to not be able to lift my leg very high in order to walk properly, altered consciousness, blurred vision, muscle pain and stiffness all along the left side of my body from the top of my head down to my feet (same feeling as if you had a blood pressure cuff on high wrapped around one side of your body), and vertigo. There might be more, but sometimes remembering the episode is vague. I remember enough of it though.
The timing for this second, more severe attack lasted through the night. I fell asleep in pain, even after taking my “abortive” meds. I do not take Triptans of any kind as they have hospitalized me in the past with a severe, week or longer lasting Hemiplegic Migraine attack. It takes months to recover from those. It’s like having a stroke and having to recuperate because the temporary damage is a little more extensive than a typical Hemiplegic Migraine attack. The abortive medication is a combination of prescription Compazine, 3 Alka Seltzer tablets, and a 25mg Benadryl capsule. My doctor at the Mayo Clinic decided this was the best option for me since I have been receptive to the same combo in the hospital through IV. It works about 75% of the time if I catch it early enough.
By the time I fell asleep I was still in a lot of muscle pain, but my head had cleared and my vision was normal. I was no longer dealing with vertigo and I could walk well enough, considering the muscle pain and light stiffness that lingered. So here is where the magic happens. The next morning, on the 20th, which is not reflected in the data since the cut off date was July 19th, I woke up completely normal. NO MIGRAINE HANGOVER whatsoever. What???!!! Seriously, guys, this is unheard of for me. With a Level 9 attack, I should have been in bed for AT LEAST 24 to 48 hours with migraine hangover. I am usually bed-bound because of it. It’s almost as awful as the migraine attacks themselves.
So while I couldn’t avoid the severe migraine attack, I woke up like a champ and went on with my day like nothing happened. To me, that’s a win. A REALLY BIG WIN! I have accepted that I will have Hemiplegic Migraine for the rest of my life, but if I can have an attack and suck at it and then wake up the next day refreshed, I’m in!
I need to take a few more sentences to say how amazing my kids are. We live directly behind my sister’s house in North Carolina. So we walk back and forth all the time to see each other. That night I walked over there but couldn’t walk back. My daughter, newly licensed, had to go to our house and drive the car over so I could get home. They were both on top of it! My son stayed with me and just hung out, checking on me every few seconds. He never left my side while Marissa went to get the car. You see, Stephen wasn’t answering any of their phone calls. While we’ve lived through this since 2004, it’s been years since they’ve had to go through a bad attack like this one alone with me.
While my sister and her family were there, they aren’t used to my attacks. We’ve only lived here since August of last year. I don’t normally leave my house if I’m dealing with HM, so nobody but my husband and kids really know the true impact of what goes on. While they were very accommodating, they let my kids handle taking care of me for the most part while we waited to go home. My kids and my sister helped me to and into the car, all the while I’m trying to talk and failing miserably.
For some odd reason, I get talkative when I have aphasia, even though nobody understands me. It’s weird that I do that. Anway, Marissa drives me home and Noah helps me out of the car and into my bed. In the meantime Marissa is putting my abortive together for me to take so I can lie down and try to sleep. I can never lie down and just sleep, though. Instead, since the attack had already started fading and most of the more serious symptoms were gone, I got online and talked to my peeps in the Migraine Support Group. The medication eventually did its job of making me sleepy and I knocked out.
My husband hasn’t been sleeping, as I mentioned earlier. The reason nobody could get ahold of him was that he was KNOCKED OUT to the world! He didn’t even wake up when we came home making all kinds of noise. My kids are rockstars, I am so proud of them for the way they held their own. They knew exactly what to do to make Mom comfy in all this pain. I just love them.
No side effects this week, other than little constipation. But I am not so sure it’s a side effect, but more of what I had to eat. Magnesium did the trick and it wasn’t an issue. It didn’t seem related to IBS in any way.
While I still have a lot more energy than I did pre-Aimovig, I have days where I feel fatigued. I can’t say my energy level is any different than Week 2. Might be a little less, but still better than before. At the beginning of Week 3, I did feel more energized. But as the week progressed, that energy slipped some. Going to keep an eye on that. Also, I haven’t been getting too much sleep. According to my sleep logs, I’m averaging about 4 1/2 hours of sleep per night. I’m almost positive that’s probably why my energy has dipped.
I have Irritable Bowel Syndrome (IBS) that occurs only during migraine attacks. This week I haven’t had any bouts of IBS with any of my attacks. Normally once an attack happens I’ll have IBS that day. None so far, with the exception of constipation I mentioned earlier. But there was no back and forth like normal.
Week 3 Wrap-Up
Well, guys, I’d say this week was pretty successful, with the exception of that Level 9 migraine attack. Though, there was still an upside at the end of it. So I count that as a win! I foresee migraine attacks still occurring next week, but I also foresee lower pain levels and shorter durations **crosses fingers**. I enjoyed my week for the most part. I got out of the house to run errands, always with a driver since I’m still not driving. I’ve been grocery shopping with no attack on the way out. Woohoo!! I’ve written more articles than normal this week. I’ve been brainstorming because the fog is gone and concepts seem clearer. All in all, Week 3 was successful in my book.
Week 4 Update (as of Thursday, July 26, 2018)
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It’s the fourth week after my first Aimovig shot and I’d say things are progressing nicely. Don’t get me wrong, I still get migraine attacks, but they are becoming further apart from each other. I did have two pretty severe hemiplegic migraine attacks within these last 7 days, which I’ll go into more detail later. Even so, I also had really low pain-level attacks and days with no attacks. So let’s get into it…
My trigger threshold isn’t as strong as it was after the first week post-Aimovig injection. My energy levels have also dipped. I’m tired all the time and I need naps to sustain me through the evening. I think that is why I was easily triggered into those two severe hemiplegic migraine attacks. The first severe attack was on 7/20/18 after I had been laying on the couch in a bad position. Bad posture is a big trigger for me, but sometimes I just forget until it’s too late. The highest pain level was a 9 and I had to take my prescribed migraine cocktail (prochlorperazine, Alka Seltzer, Benadryl). I did have a difficult time falling asleep, but by morning the pain was completely gone like nothing had happened. I was so surprised, it always takes me at least 48 hours to recuperate from an HM attack of this magnitude. It was like it never happened.
My next attack wasn’t again until 7/23/18, but was not a hemiplegic migraine. I did have migraine with aura at a pain level of 4 until the next day. I was fatigued after and slept until late morning on 7/24/18. I didn’t take any meds this time around, I try not to take them too often. I don’t work, so I was able to sleep through it.
A few days later, on 7/25/18, I had another severe hemiplegic migraine attack at a pain level of 9. The day was very raining and stormy and the humidity was at 90%. Not good for a person with migraine who has barometric pressure change triggers. During this attack I suffered through altered consciousness, severe pain all along the left side of my body (muscle pain), vertigo, aphasia, and hemiparesis. The attack happened at 9:25 pm after I really good day. No pain or migraine attacks at all until after leaving the movie theater. I was walking out of the theater on the way back to the house. I wore migraine glasses during the movie because I had already started having light sensitivity right before the movie started. I really wanted to see Equalizer 2, so I stayed knowing I was going to have an attack at some point. I just underestimated how bad it would get. By morning it was gone. Again, I was completely normal like nothing had happened the night before. I’m so not used to that! No migraine hangover whatsoever!!
I know I will have hemiplegic migraine attacks, I have accepted that. But to have no disabling migraine hangover for days after? That’s a game changer!
Side Effects & Energy Levels
No side effects this week. It seems any side effects have worn off completely. Although, the energy I did have after the shot has also worn off. I do have more fatigue. I’d rather have that than migraine, though.
No change from Week 3: I have Irritable Bowel Syndrome (IBS) that occurs only during migraine attacks. This week I haven’t had any bouts of IBS with any of my attacks. Normally once an attack happens I’ll have IBS that day. None so far, with the exception of constipation I mentioned earlier. But there was no back and forth like normal.
Week 4 Wrap-Up
I know I had a couple of severe attacks, but the migraine hangover continues to stay absent and pain levels stay low for the most part. The length of attacks is also shortening. I am wondering if the fatigue returns because the shot is “wearing off” or if it is, indeed, a side effect I’m excited to see what happens next month after Dose #2!!
I use Migraine Buddy to track my attacks pretty consistently. Below is a table showing up-to-date data as of July 26, 2018. Keep in mind, on some nights I fall asleep with an active attack and wake up attack free. The counter counts the next morning since I don’t END the migraine attack until I actually wake up the next day.
**Raw data from my Migraine Buddy app as of July 26, 2018
The top portion of the table above, in the greyed-out rows, shows each month, March through June. These months are pre-Aimovig injection. July to the Present is post-Aimovig injection. The table reflects the following data within the given time period in the first column:
- Number of Days
- Number of Migraine Attacks
- Number of Attack Days
- Number of Attack-Free Days
- Average Attack Duration
- Average Pain Intensity
- Minimum Pain Intensity
- Maximum Pain Intensity
I’ve included screen captures from the Migraine Buddy app installed on my phone. This is the raw data captured by the app and created into nifty charts to share with doctors, and you of course! This data should coincide with the numbers you see in the table above. Also, I’ve added marks next to the stats that are updated as of July 26, 2018. Look for these each week to see what’s new.
Note: All stats notated with two ** are current as of this week’s update.
Disclaimer: I was a paid Amgen and Novartis Spokesperson. This content reflects my own personal opinions and was not created or reviewed by Amgen and Novartis. I was not paid to write this article.
Articles Where “Aimovig” Appears:
- Aimovig Monthly Update (Month 2)
- Aimovig Monthly Update (Month 3)
- Aimovig, Medicaid, Medicare, and the Uninsured
- Writing a Letter to My Inconsistent Brain
- Mental Slump = Physical Exhaustion
Aimovig: Community Feedback & Experiences
“I have daily severe intractable migraines. My first two Aimovig injections were 70mg. While the severity of my migraines decreased, I never had even one migraine-free day. So for my third injection we bumped up to 140mg. No change. I was ready to throw in the towel but my doctor urged me to give it one more try and boy am I glad he did! Had the injection last Friday and have been migraine-free ever since, which is nothing short of a miracle.”
“I think the drug might actually be working. My pain level has been 0-5 with most leaning towards low end. Prior to Aimovig it was 8-19 every damn day. Hope I didn’t just jinx myself!!”
“12 days since two shots of Aimovig and I’ve only gotten 2 migraines! That’s great for me. I feel like migraines are trying to start, but then they never do.”
“I had a bad migraine with the 70 mg. No side effects. Happier with the higher dose. Time will Tell.”
“I am on month 2 of Aimovig. The first month I only saw a small improvement in my daily migraines. This month I have had much better results!! I can’t say I have been headache free yet (I have had a daily headache for over 2 years) But I can say that I am feeling much better than I have in 2 years!”
“This is the first preventive drug that has ever worked for me. Definitely give it 30 days if not 60, if you can.”
“I’m almost 3 months in with Aimovig and have gone from 12-15 migraines a month to zero (3 if you count a few mild instances that cleared within 12 hours). I didn’t think Botox was helping much before Aimovig, and suspect dropping the Botox would have little effect, but another part of me wants to change nothing while I’m getting such relief.”
So far little to no change
“I have had NDPH/ chronic intractable migraine for 5.5 years. I had 2 of the 70mg injections as part of the trial, and just had my third dose 4 days ago which was the first time had 140mg. Still zero benefit. If this doesn’t work, the next might, or a different anti-CGRP med might work.”
“I’m two weeks past my third 140 mg dose and no changes to my chronic migraines symptoms, which are daily. I recognize the clinic research identified that improvements may not be experienced until after the fourth dose, but my side effects are escalating with each dose.”
“I just had my 2nd treatment of Aimovig a few weeks ago and absolutely no change. I’m having them worse than ever! I am also itching terribly. I mentioned this to my neurologist and she said even though it’s listed as a lesser known side effect none were reported in trials so it’s not the Aimovig.”
“I’m officially done with Aimovig and boy do I regret taking that last injection! I’m daily severe intractable so I’m pretty damn desperate….I’m on week 6 of going off and still triptans don’t work at all. Plus I’m back to 14 hour migraines every day.”
“I have had three doses with no improvement (plus side effects) and am strongly considering not continuing with fourth dose.”
“The lst does of 70 did not do anything. Two weeks ago I had the 2nd injection and then a few days after that had yet another round of Botox as my Neurologist thought the double punch might help…nope, nothing.”
“It’s only been two months, but I think I’m one of the people it doesn’t work for, at least not at the 70mg dose. I’ve had worse migraine pain since starting it than usual, and no noticeable reduction in migraine days.”
“I only tried one injection of Aimovig And it gave me awful side effects…I also have fibromyalgia but the injection made it 10 times worse on a daily level. Plus I experienced the constipation which I can’t afford…. even with stool softeners. My doctor decided that it was not for me..”
“I was using Botox and getting relief for about 3 months after the injection, then the migraines would reappear. I switched to Aimovig in July. It worked well until October. Now the migraines are back.”
Side effects from Aimovig
“I have experienced mild stomach queasiness, dizziness and even vertigo like symptoms, as well as extreme lethargy – beyond what is “normal” for me as someone with chronic illness.”
“I am having terrible side effects since my first shot a few days ago. Dizziness, nausea, insomnia, and worst of all the worst migraines of my life everyday.”
“I haven’t noticed any side effects from Aimovig and seems to be the first solution in my 30 years of migraines. Weather (pressure) change is my trigger.”
“I too am experiencing muscle aches and profound fatigue.”
“I have had no side effects after 2 weeks.”
“I have always had muscle pain (neck, shoulder, traps) associated with my migraines, however since starting the Aimovig 2 months ago my muscle pain has been unbearable.”
“I’ve had three injections. The only thing I’ve noticed – and I’m not sure if it’s a coincidence or side effect – my joints are stiff and ache all over.”
“Approximately 3 minutes following the 1st injection of Aimovig (in the my right thigh), my lips from midline to the right went numb and tingled as did my right shoulder.”
“My body had a severe response to Aimovig. My Immune system recognized the drug as a poison, and made antibodies to destroy the drug.”
“The first 24 hours I felt light headed from time to time. Has not recurred since. My headaches have gone from 15-20 headache days/month to 5-6 days/month. I’m on the 70mg dose.”
“Have not been able to sleep at all since the injection and constipation as well.”
“My triptans stopped working since taking the Aimovig.”
Let’s keep the conversation going
How about you, have you tried Aimovig? If so, we’d love to hear your feedback & experience in the comments below or in our forum page here.
Do The New CGRP Drugs Work For Migraine?
5.What are the clinical results of using the new CGRP drugs? The results of the three drugs are similar and they all seem to work well, and about the same. Fifty percent of patients have fifty percent reduction of migraine attacks. Twenty-five percent of patients have 75 % reduction of migraine attacks and another 20-30 percent of patients are super responders with 100 % reduction of migraine. It seems the drugs work better as time goes on, better at 4 months than at 1 month.
6.Are doctors required to check blood parameters for patients taking CGRP antibodies? No medical monitoring or blood work is required for the new drugs.
7.How do the new CGRP drugs compare with older preventive drugs? The older drugs used by neurologists for migraine prevention are: Inderal (propranolol), Atenolol, topiramate, dialprovex, and amitriptyline and nortriptyline. Inderal could drop the blood pressure and pulse and cause a “tired syndrome.” Topiramate may cause start up symptoms of finger/lip tingling, a “Coke tastes flat” problem, and cognitive/word finding issues so that patients called the drug, “Dopamax.” Amitriptyline, at low dose of 10-20 mg taken at night, could give a dry mouth, constipation, or weight gain.
These drugs have always had a lot of side effects and only reduced migraine 30-40, sometimes 50 % of the time. Patients would start out strong and then by 3-4 months they would stop taking the drugs. Some of them using amitriptyline for sleep and migraine prevention would hang on to amitriptyline to treat insomnia.
All of these drugs had to be taken daily. In drug trials for the CGRP drugs 89 % of patients stayed on the subcutaneous, once a month treatment, while 40 % of patients taking one of the older drugs would be off treatment by 4 months.
8.Are CGRP drugs safe for persons with hypertension, coronary artery disease, heart attack, stroke, or TIA problems? Yes, the new CGRP drugs are safe for the listed problems. Triptans, the best drugs for acute therapy for migraine are contraindicated for these problems, but CGRP antibodies are safe.
9.How long does it take the body to metabolize these CGRP drugs? The half-life of Aimovig is 28 days, Emgality-28 days, and Ajovy-31 days.
10.What is the expense/insurance coverage of these drugs? I tell patients that I struggle and work hard to learn neurology and headache, but I don’t do insurance, which is a very complicated, multifaceted process.
Aimovig was the first CGRP drug released and available in Dallas in July 2018. They had a much more restricted group of insurances they accepted first, but then the other drugs quickly came out, Ajovy and then Emgality, and the insurance coverage situation improved. There’s nothing like a free market and competition to prod insurance companies to change.
Aimovig in the U.S. costs $6,900 annually. Persons with insurance are being covered, while the non-insured and Medicare patients are not being covered. It usually takes 20 years for the patent on a brand name drug to expire and the drug to become generic.
11.What about use of the new CGRP antibody drugs for pregnancy or lactation? There is no current indication for the use of CGRP antibody drugs during pregnancy or while breastfeeding. The FDA statement regarding CGRP antibody drugs is:
Pregnancy-caution is advised during pregnancy. No human data is available, no known risk of fetal harm based on animal data at 20 times recommended human dose.
Lactation–caution is advised for breast-feeding. No human data available to assess risk of infant harm or effects on milk production.
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All the best.
Follow me at: www.doctormigraine.com, Pinterest, Amazon books, and YouTube.
Britt Talley Daniel MD
Lawrence Robbins, M.D.
NOTE: This is a shortened version of an article published in the March issue of Practical Pain Management (available online).
Migraine is a relatively common illness, affecting 12% of the population. Chronic migraine (CM) is a frequently encountered subset of migraine, and presents certain difficulties in treatment. Those with CM have at least 15 headache days per month, with at least 8 days being migrainous in nature. In addition, medication overuse headache cannot be a major contributing factor to the headache pattern. Many with CM do not do well with the usual preventive approaches, and suffer from refractory chronic migraine (RCM). Patients with RCM have failed on at least 3 types of preventive medications. A number of our usual migraine preventive approaches have limited efficacy, and side effects often limit use. Additionally, effectiveness often diminishes over time. New preventive approaches are needed for chronic migraineurs.
Calcitonin gene-related peptide (CGRP) is an important neuropeptide involved in the migraine process. CGRP receptors are ubiquitous in the sites that are involved in migraine pathogenesis. CGRP is involved in mast cell degranulation, neurogenic inflammation, and the subsequent vasodilation. During a migraine, CGRP levels usually rise. For those with migraine, infusions of CGRP may precipitate an attack. During a migraine, trigeminal nerves that are activated may release CGRP, as well as other inflammatory compounds. The monoclonal antibodies (mAbs) that inhibit CGRP have been effective for a number of patients with chronic migraine.
Our current oral migraine preventives include antidepressants, anticonvulsants, and medications used for hypertension. These have limited efficacy, and often are not tolerated. Onabotulinumtoxin A is more effective than the oral preventives, and has few side effects. For those with chronic migraine, there is a need for more effective preventives. The CGRP monoclonal antibodies that may help to fill that role.
Erenumab-aooe (referred to as erenumab in this article), was the first CGRP mAb to become commercially available, in May of 2018. Erenumab is a subcutaneously administered once-per-month injection. There are currently 2 other mAbs available: fremanezumab and galcanezumab. These are all large molecule mAbs, with little penetration through the blood brain barrier. Erenumab targets the CGRP receptor, while the others in this class affect the CGRP ligand. These large molecule mAbs have several major advantages, including little or no drug interactions. In addition, they are cleared through the reticuloendothelial system, and do not irritate the liver or kidneys. Demand for these newer preventives has been brisk, as there has been a paucity of effective therapies for those with chronic migraine.
We evaluated the results of erenumab after the first 6 months of treatment. The first study involved 220 consecutive chronic migraine (CM)patients, after 3 months of therapy. 43% of all patients experienced 0 to 30% relief. 34% reported 30 to 70% relief, while 24% described 70 to 100% relief. Among the 43% with only 0 to 30% relief, many did choose to continue with erenumab. Many of these patients did state that they were satisfied with 15 to 30% relief. Forty-eight patients dropped off of the erenumab after months 1 or 2. Ten percent of patients reported almost complete (95 to 100%) relief over the 3 months. The patients in this study were relatively more refractory than those in the Phase 3 erenumab studies. These patients had all utilized at least 3 preventives, and almost all had tried onabotulinumtoxin A. One hundred thirty-two of the patients were considered to have refractory chronic migraine. In this study, the efficacy of erenumab was reasonable, even considering the relatively refractory population. We do not know how efficacy will hold up over time.
There were a considerable number of side effects reported by the 220 patients. Constipation was the most prevalent, at 20%. The constipation was severe in some patients, requiring treatment. At least 4 patients discontinued the erenumab primarily due to constipation. Nausea (7%) was also described, as was an increased headache (5%). The nausea usually resolved, but with an increase in headaches, the erenumab was usually discontinued. Fatigue (5%) was sometimes severe, requiring discontinuation of the medication. Joint pain (3%) sometimes accompanied the severe fatigue.
Depression (3%) was sometimes exacerbated after erenumab was started. Anxiety (2%) also occurred was described. Diarrhea was seen in 2% of patients, and several patients experienced severe diarrhea. Injection site reactions (2%) were mild, not requiring discontinuation.
We observed 3 serious side effects. One 21-year-old had a probable migraine-related stroke. Her cognitive symptoms have improved, but she is left with mild to moderate dysgraphia. She had a history of hemiplegic migraine (although none for 3 years), and had been using erenumab for 4 months. She was also on a low dose birth control pill that contained estrogen. The second patient is a 31-year-old with severe neurologic symptoms, which began 2 weeks after her 2nd erenumab injection. She also suffered from severe fatigue, with joint pains. Symptoms did eventually resolve (but they recurred 3 months later, off of the medication). The third patient suffered severe fatigue and joint pain 3 weeks after receiving the erenumab. She had a history of rheumatoid arthritis, which had been in remission. She eventually improved with corticosteroid therapy. The erenumab was probably a factor in these serious side effects. Serious side effects are a major concern with these CGRP monoclonal antibodies.
The second study evaluated 26 poor responders (0 to 15% relief) versus 26 patients with an excellent outcome (70 to 100% relief). Both of these groups consisted of relatively refractory patients, with a history of headaches that averaged 28 years. The location of headaches for both groups was primarily both anterior and posterior. Sixteen of the 26 in the poor response group reported neck pain, and 10 in the excellent group. Central sensitization syndromes were more commonly encountered in the excellent group (11 vs. 5 patients). Most patients suffered from anxiety. Depression (15 in the poor group, 17 in the excellent group) was frequently encountered, although less than anxiety. Insomnia was commonly encountered as well. Sixteen of the poor response group was considered to have refractory chronic migraine, while only 7 in the excellent group had been diagnosed with RCM. The poor response group was more likely to have moderate (6 vs. 2) or severe refractory chronic migraine (6 vs. 1) than in the excellent response group. This author has published on separating RCM into mild, moderate, and severe. We used a 10-point scale to determine the level of refractoriness. It may be clinically useful to separate refractory patients into these different levels. All of these patients had tried onabotulinumtoxin A therapy. Eight of the poor group had responded well, while 12 in the excellent group did well with onabotulinumtoxin A. A number of the patients continued with onabotulinumtoxin A, along with the erenumab. The majority of patients had a positive response to triptans. In the poor response group, 18 had good responses to opioids, while only 8 of the excellent group responded to opioids. A number of the patients had responded well to butalbital compounds (12 and 10 patients).
The third study evaluated those 50 patients who had completed 6 months of therapy. The average relief started with 36% and 35% for the initial 2 months, but slowly declined to 27% by the end of the 6th month. Patients who averaged 0 to 15% relief for the first 2 months were assessed. They continued to do poorly, with 13/15 patients experiencing 0% to 15% after 6 months. Only one patient improved significantly over time. Similarly, most of the patients(N=9) who did very well (70% to 100% relief) for the first 2 months generally continued to have success. After 6 months, 6 of these 9 patients maintained the excellent relief.
The 2 main issues with CGRP mAbs for migraine prevention are: 1. will these remain reasonably effective over time, and 2. what is the true side effect profile. The efficacy question will only be answered after several more years of treatment. Regarding side effects, this author has major concerns about the various risks that could arise due to blocking of CGRP on a chronic basis. The following are some concerns.
CGRP most likely is an inhibitor of platelet aggregation. Blocking this effect may increase the chance for cardiac or cerebrovascular effects. As of Sept. 30th, 2018, there were at least 6 cerebrovascular events listed on the FDA site. This author has put in a Freedom of Information Request for details on those events. This author has heard about several other erenumab-related strokes, yet to be officially reported, in addition to the one reported in this study.
CGRP plays some role in the prevention of hypertension, and may be somewhat protective for cardiovascular disease. CGRP is a powerful vasodilator, particularly in the meningeal and cerebral arteries. Blocking CGRP may lead, under certain circumstances, to intracerebral vasoconstriction. It is possible that other related compounds, such as amylin or adrenomedullin, may help compensate for the loss of CGRP. In addition, various vasodilators may also help to mitigate negative effects from CGRP antagonism. These include nitrous oxide, vasoactive intestinal peptide, and others. CGRP also is important in neovascularization. CGRP enhances recovery from ischemia by stimulating angiogenesis. CGRP helps to prevent secondary lymph edema, and enhances lymphangiogenesis. The adverse health consequences on the above systems, by blocking CGRP, are unknown.
The effects of CGRP mAbs on hormones has not been studied. The hypothalamus and pituitary are not, for the most part, protected by the blood brain barrier (BBB). CGRP is present in these areas. In theory, CGRP antagonism could result in various hormonal effects. The choroid plexus, involved in CSF production, also is not protected by the BBB. In addition, the area postrema, involved in nausea and vomiting, is not protected by the BBB. Circumventricular organs, important in homeostasis of various functions, are also not protected. Studies have yet to be done regarding the effects of CGRP mAbs on these areas.
CGRP is involved with skin blushing, flushing, cold sensitivity, itch, edema, and thermoregulation. After surgery, or after a serious burn, healing may be impaired by the CGRP mAbs. CGRP does play a role in the metabolism of bone, and is involved with bone healing. In diabetics, by antagonizing CGRP, there may be a higher risk for coronary artery disease. In the GI tract, CGRP has myriad functions. CGRP is involved in motility, and in protecting the gastric mucosa. Constipation may occur with CGRP antagonism, and to a lesser degree, diarrhea. None of the above effects have been studied, with regard to the CGRP mAbs.
We do not want to use these medications during pregnancy. There may be more risk to the CGRP mAbs in later stages of pregnancy. Preliminary studies in animals have not revealed major issues with the newborn animal.
A number of patients have reported severe fatigue from erenumab. Additionally, joint pain has been an issue for some patients. It is possible that the hypothalamic-pituitary-adrenal (HPA) axis may be involved with these side effects, as the HPA axis is not protected by the BBB. There have been no studies of CGRP mAbs and the HPA axis.
As of December 31, 2018, 7300+ possible side effects had been reported to the FDA; over 800 were deemed serious. Only a fraction of side effects are officially reported to the FDA. It is very concerning that we have a paucity of studies on the serious consequences of blocking CGRP for long periods of time.
Until we know more, it is prudent to screen patients for risk. Informed consent should be obtained. Patients at increased risk may include those with risk factors for stroke, including the usual risk factors (lipids, HTN, diabetes, family history, cigarettes). In addition, at higher risk may be patients with clotting abnormalities, positive lupus anticoagulant, or positive anticardiolipin antibodies. It is possible that hemiplegic migraine, or those with frequent auras, may represent an increased risk as well. Certain birth control pills may be a problem, although this is controversial. Patients with recent surgery, or who have suffered a recent fractured bone, should possibly delay the use of the CGRP mAbs. Those with active GI ulcers, or with inflammatory disease of the GI tract, may also be at an increased risk. Because of the possible hypothalamic and pituitary effects, patients with various hormonal issues may be affected. The effects on bone growth, as well as on hormones, cautions against using these treatments in children and adolescents. We need studies in all of these areas.
There are major limitations to this study. It is retrospective, and studies #2 and #3 had limited numbers of patients. The patients are relatively refractory, as compared to most migraineurs. We relied on diaries and calendars, as well as patients’ self-reported histories. These are not always accurate. Most, but not all, of the patients maintained calendars of their migraine days. We were not able to ascertain whether each of the reported side effects was due to the erenumab. This is basically an observational study, with no control group.
The major strength of this study is that the patients were not selected for any purpose other than migraine treatment. They represented a “real life” group of migraineurs, albeit relatively refractory. We also were able to tease out and complete an analysis of poor responders vs. excellent responders. The 6- month results may be helpful in understanding efficacy over longer periods of time.
References/ For Further Reading
- Lassen LH, Haderslev PA, et al. CGRP may play a causative role in migraine. Cephalalgia 2002; 22:54-61
- Tepper, S. Anti-Calcitonin Gene-Related Peptide (CGRP) Therapies: Update on a previous review after the American Headache Society 60th Scientific Meeting, San Francisco, June 2018. Headache 2018; 58:276-290
- Reuter U. Anti-CGRP antibodies: a new approach to migraine prevention. Lancet Neurol. 2014; 13(9):857-859
- Tepper SJ, Ashina M, Reuter U, et al. Safety and efficacy of erenumab for preventive treatment of chronic migraine: A randomized, double-blind, placebo-controlled phase 2 trial. Lancet Neurol 2017; 16: 425-434.
- Goadsby PJ, Reuter, U, et al. A controlled trial of erenumab for episodic migraine N Engl J Med 2017; 377:2123-2132
- Dodick DW, Ashina M, et al. ARISE: A Phase 3 randomized trial of erenumab for episodic migraine. Cephalalgia 2018; January https://doi.org/10.1177/0333102418759786(Epub ( ahead of print)
- Reuter U, Goadsby PJ, et al. Efficacy and safety of erenumab in episodic migraine patients with 2-4 prior preventive treatment failures: Results from the Phase 3b LIBERTY study. Emerging science platform presentation and poster 009. American Academy of Neurology meeting, Los Angeles, April 24, 2018(abstract).
- Depre C, Antalik L, et al. A randomized, double-blind, placebo-controlled study to evaluate the effect of erenumab on exercise time during a treadmill test in patients with stable angina. PO-01-198. Cephalalgia 2017; 37(Supplement 1):340-341.
- Tepper SJ, Pascual J, et al. Analysis of blood pressure following short-term and long-term treatment with erenumab. Poster 105. 68th American Academy of Neurology meeting, Los Angeles, CA, April 25, 2018(abstract)
- Headache classification committee of the international headache society (HIS). The international classification of headache disorders, 3rd edition (beta version). Cephalalgia 2013.
- Refractory chronic migraine: a consensus statement on clinical definition from the European Headache Federation. J Headache Pain 2014; 15:47.
- American Psychiatric Association (2013). Diagnostic and statistical manual of mental disorders (5th edition), Washington, D.C.
- Robbins, L Refractory chronic migraine: long-term follow-up using a refractory rating scale. J Headache Pain 2012; 13:225-229.
- Matsumato Y, Ueda S, et al. CGRP inhibits human platelet aggregation. Japan Circulation J 1996;60(10):797-804.
- FDA Medwatch adverse drug site: fda.gov/safety/medwatch (erenumab aooe).
- Russell, FA, King, R et al. Calcitonin Gene-Related Peptide: physiology and pathophysiology Physiol Rev 2014;94:1099-1142.
- Majima, M, Ito, Y, et al. CGRP/CGRP receptor antibodies: potential adverse effects due to blockade of neovascularization Trends in Pharmacological Sciences 2018 (e published) https://doi.org/10.1016/j.tips.2018.11.003
- Brain S, Grant A Vascular actions of Calcitonin Gene-Related Peptide and Adrenomedullin Physiol Rev 2004;84:903-934
- Deen M, Correnti E, Kamm K, et al. Blocking CGRP in migraine patients-a review of pros and cons. J Headache and Pain 2017;18(1):96.
- Gangula PR, Zhao, et al. Pregnancy and steroid hormones enhance the vasodilation responses to CGRP in rats. Am J of Physiol Heart Circ Physiol 1999;276:H284-H288.
New Migraine Drug Approved: Four Things Health Execs Need to Know
A newly approved drug shows promise for people who have unsuccessfully tried to prevent migraine headaches with other treatments. Findings from a preliminary study of Aimovig (erenumab), the new drug, on 246 people who had episodic migraine were presented at the American Academy of Neurology’s (AAN) annual meeting in April.
“The people included in our study were considered more difficult to treat, meaning that up to four other preventative treatments hadn’t worked for them,” says study author Uwe Reuter, MD, medical director at the Charite-University Medicine Berlin in Germany. “Our study found that erenumab reduced the average number of monthly migraine headaches by more than 50% for nearly one-third of study participants.”
Those treated with Aimovig also had a greater average reduction in the number of days they had headaches and the number of days they needed to take drugs to stop migraines.
Lawrence C. Newman, MD, professor of neurology and director of the headache division at NYU Langone Health in New York, NY, who attended the AAN meeting and heard the presentation about the new drug, says there hasn’t been a new medication to treat migraines for 50 years. “The drugs we have don’t work for everyone and may cause significant side effects,” he says. “Because we don’t have a cure for migraines yet, and because no one medication works for everyone, new treatments are necessary for the 36 million people who suffer from migraines.”
Here are four things health execs should know about the new drug.
- The new drug works differently than other migraine medications.
Aimovig is a drug in a new class of medications called calcitonin gene receptor peptide (CGRP) monoclonal antibodies. CGRP is one of the neuropeptides that is released during a migraine and leads to pain, inflammation, and dilation of blood vessels.
It is a subcutaneous injection given once a month in one single injection dose. “Physicians don’t have to worry about adherence, since it’s only a once-per-month injection,” Newman says.
2. The medication is used to prevent migraines. Monoclonal antibodies are used to prevent migraine attacks; they are not meant for someone to take when they have signs of a migraine, such as sensitivity to light and sound, disturbed vision, nausea, and vomiting.
“This is the first treatment developed specifically for migraine prevention,” says Katherine S. Carroll, MD, neurologist, Northwestern Memorial Hospital, Chicago, Ill. “Prior to erenumab, medications used for other purposes (e.g., anti-hypertensive medications, anti-depressants, and anti-epileptics) were used because they were also found to be helpful in preventing migraines.”
Reuter points out that people who take the drug might still get acute migraines, and will need to take triptans (i.e., serotonin receptor agonists) to prevent them when they have signs of getting one. But they won’t need triptans as frequently.
3. The new drug has fewer side effects. The side effects include injection site irritation for a few hours or upper respiratory symptoms. “It doesn’t cause any cognitive effects, weight loss, or weight gain like some other migraine medications,” Newman says.
Typical migraine medications take about six weeks to exert efficacy. “Patients sometimes have to undergo weeks of trial and error until we determine the best dose of a medication to sustain effect, but migraine physicians should know within a week if this medication works for a patient,” he says.
4. The new drug will probably cost more.
The new drug will likely be more expensive than current medications. “So it probably won’t be a first line choice for everyone,” Reuter says.
Although this new treatment option may be quite costly, it could lower the overall costs for migraine treatment by preventing frequent emergency department visits and hospitalizations that patients with unmanageable migraines often have, Carroll says. “Improved migraine control leads to less time off work and less disability.” In addition, fewer migraines could lead to better overall mental health and less depression and anxiety—which are common comorbities in people who suffer from chronic migraine pain.
The drug received FDA approval May 17.
Karen Appold is a medical writer in Lehigh Valley, Pennsylvania.
Suffering from migraines is a serious health problem suffered by 39 million Americans. Migraine symptoms like nausea and throbbing pain actually disable 1 in 5 people who get them. These people are forced to call off from work, cancel plans with friends, and writhe in pain until the migraine finally ends.
It is possible that the FDA just transformed the ability for migraine sufferers to seek relief by approving Aimovig, the first in a new class of migraine drugs that aim to fight migraines before they start. If you have multiple migraine days a month, this medication could change your life.
How Does Aimovig Work?
Aimovig works by blocking calcitonin gene-related peptide (CGRP), a molecule that’s produced in nerve cells of the brain and spinal cord. According to Dr. Richard Lipton of the Montefiore Headache Center, “We’ve believed for a long time that CGRP played a very important role in migraine, and part of the reason we believed that is because when people get a migraine attack, we can measure elevations of CGRP in their blood.” Though CGRP is not believed to trigger migraines, it intensifies headache pain by making the nerve cells more sensitive to pain input.
How Effective Is Aimovig?
Aimovig is given as a monoclonal antibody self-injected shot. “Monoclonal antibodies are designed to prevent migraine attacks from occurring. They don’t necessarily prevent every attack because there are attacks that can break through. But they reduce the frequency of these episodes,” according to David Odick, M.D., a chairman at the American Migraine Foundation.
In all, studies indicate that Aimovig has the potential to cut migraine days in half. A small percentage of patients in the trial studies actually saw their migraine headaches eliminated altogether.
What Else Should You Know?
Unlike current migraine drugs that cause very unpleasant side effects like constipation, weight gain, dry mouth, and nausea, Aimovig’s side effects are mild and usually limited to redness after the shot. Aimovig also works quickly so you are likely to see results within only a few days to a week.
If you’re interested in learning more about this new treatment to limit your own migraine days, be sure to speak with your doctor first. Call (727) 525-0900 to make an appointment with Dr. Kavita Rao, M.D. in St. Petersburg, Florida. Dr. Rao will evaluate your overall health and migraine patterns to determine if Aimovig is right for you.
On July 31, 2018, the Daily Mail of London wrote about the Stanton Migraine Protocol and how a simple dietary change can help prevent migraines. The journalist became curious about the topic because a migraineur gave a testimonial about this protocol on YouTube. The paper started off with:
The conventional advice — backed by everyone from the NHS to the British Heart Foundation and the Scientific Advisory Committee on Nutrition — is to reduce salt intake where possible, owing to its links with high blood pressure, heart disease and stroke.
The official guidance is that we should eat no more than 6g of salt a day, which is around a teaspoonful. But Tracey, from Stretford, near Manchester, is one of a growing number of people following a controversial plan devised by a U.S. neuroscientist which involves eating twice that amount — with occasional extra scoops of ‘emergency salt’ — in a bid to keep migraines at bay
Thus, the topic of taking extra salt was critically viewed as a recognized health concern. The same article concluded:
However, there is now a preventive drug specifically developed for migraine called Aimovig.’ This has just been approved by the European Medicines Agency and ‘should soon be on prescription from GPs’.
The Migraine Trust advises consulting a GP first if you are considering consuming more salt.
Let me spell out what these quotes demonstrate exactly. Currently, most medical professionals consider taking a brand-new drug safer than taking of a bit of extra salt.
Salt and Health
Salt is in every human cell taking up about 0.4% of the body’s weight and is an essential mineral for survival. We lose salt by sweating, talking, breathing, and by our internal toxin removal processes making daily salt consumption essential for remaining healthy. The 6 gr salt amount recommendation by the above mentioned agencies and the USDA has been debated to be too low for health for years. For instance, an article in the academic journal The Lancet found that about 10 gr salt (4 gr sodium) is the ideal amount for those with heart events and even more for those whose hearts are healthy1. It also shows that at 3 gr salt (1.2 gr sodium) or less per day, an individual’s health takes an exponential turn for the worse and fatalities may occur. A Headache journal article found that there is an inverse relationship between salt consumption amount and migraine—meaning increased dietary sodium reduces the occurrences of migraines2.
I have yet to see the claim “essential” placed on a medicine, yet without hesitation many medical professionals view medicines a safer option than an essential mineral we must consume every day.
Medicinal Migraine Treatments
Migraine is a very painful and disabling condition that about 15% of the population endures, often daily, for many years. Up until now, there have been no migraine preventive medications on the market and migraine sufferers are prescribed a host of dangerous medications, cocktails of them, originally intended for other health conditions.
- Anticonvulsants (anti-seizure medications)—Topamax, Neurontin, or Lyrica;
- Tricyclic antidepressants (simple serotonin)—Amitriptyline or Nortriptyline;
- SSRIs (selective serotonin reuptake inhibitors)—Lexapro or Zoloft;
- Beta blockers or ACE inhibitors—Propranolol or Toprol;
- Opiates—codeine, fentanyl, hydrocodone;
- Triptans—Imitrex, Frova, Maxalt, etc.;
The universal complaint from migraineurs across the board is that none of these medicines works and that they have debilitating side effects. Will Aimovig™ be different and help migraineurs? And, more importantly, will it be safe?
Aimovig™ (AMGEN, Novartis) was approved by the FDA as the first migraine preventive medicine on May 17, 2018. The medicine is a CGRP receptor agonist. CGPR stands for Calcitonin Gene-Related Peptide Receptor. Calcitonin gene-related peptides have major roles in the central nervous system (CNS) and throughout the body. CGRP is a protein that modulates a variety of physiological functions, such as respiratory, endocrine, gastrointestinal, immune, and cardiovascular function. CGRP also affects the thyroid. Calcitonin acts to reduce blood serum calcium, and thus blocking it, would likely increase serum calcium. The increase in serum calcium is undesired. Too much calcium in the blood can weaken bones, and participates in atherosclerosis, which is the calcification of the arteries, causing hardening—this is referred to as coronary artery calcification.
Some nerve blockers, like Botox, have been demonstrated to block CGRP as well. CGRP modulates cyclic adenosine monophosphate cAMP, a messenger that is important in many biological processes. It is a derivative of ATP and used for intracellular signaling. CGRP is a potent hypotensive peptide—it is a vasodilator3.
CGRP blockers work by reducing stimulus that would reach nociception. Nociceptors detect noxious or harmful stimuli everywhere in the body and signal this stimulus by pain. Aimovig™ specifically targets nociceptors and prevents them from discovering harmful stimuli.
“In some conditions, excitation of pain fibers becomes greater as the pain stimulus continues, leading to a condition called hyperalgesia” (see here).
Hyperalgesia means that the receptors become increasingly sensitive to pain over time (see here). For example, opioid-induced hyperalgesia may develop as a result of long-term opioid use4. This suggests that long term use of Aimovig™ may also induce hyperalgesia. This was not studied in the clinical trial. CGRP blocking may pose a risk in subjects with comorbidities such as cardiovascular diseases.
It is important to recall how SSRIs work (see my previous article on how inhibitory systems can cause life threatening health conditions by permanently blocking channels), because it appears that Aimovig™ acts similarly. A journal article describes the findings on Aimovig™ (there labelled as Erenumab/AMG334) alongside with other anti-CGRP monoclonal antibody trials by other pharmaceuticals. The research data of the clinical trial was released to the scientific community with an appendix providing the details. one can also get a pretty good idea of the information the FDA considered or received to be considered from the FDA label and from descriptions of competing products for which the information was released5,6.
At the Aimovig™’s website, there is a video of slide presentation for healthcare professionals, from which I created a transcript. You can find the slides on this page.
- CGRP signaling plays a key role in migraine pathophysiology by modulating nociceptive signaling within the trigeminovascular system.
- Aimovig™ is a 100% human monoclonal antibody designed to help prevent migraine by targeting and blocking the CGRP receptor
- Aimovig™ binds to the CGRP receptor and antagonizes CGRP receptor function
- “Although the exact role of CGRP in migraine has yet to be determined, compelling evidence supports its involvement. First, CGRP levels have been shown to increase significantly with migraine and decrease with headache relief post sumatriptan treatment. Second, intravenal infusion of CGRP induces migraine-like headache in migraine patients, demonstrating that CGRP may play a causal role in migraine.
- Prior to the study, participants who have not received any benefits from other migraine treatments (categories listed above) were excluded from the study.
- In Studies 1, 2, and 3, 1.3% of patients treated with Aimovig™ discontinued double-blind treatment because of adverse events. Although only injection site irritations are reported by the FDA, the study indicates additional adverse effects, such as cold, upper respiratory tract infection, ankle fracture, viral gastroenteritis, sepsis, colitis, vestibular neuronitis, backpain, migraine, ovarian cyst, and sinusitis. One person also experienced cerebral venous thrombosis (see table 3). The most frequent injection site reactions were injection site pain, injection site erythema, and injection site pruritus—as per the label. Interesting to note that constipation and site irritation are listed as side effects on the label.
- As with all therapeutic proteins, there is potential for immunogenicity. (Immunogenicity is the ability of a particular substance, such as an antigen or epitope, to provoke an immune response in the body of a human and other animal. In other words, immunogenicity is the ability to induce a humoral and/or cell-mediated immune responses; source Wikipedia) “A total of 35 of the 628 patients (5.6%) for whom postbaseline antibody data were available tested positive for anti-erenumab binding antibodies (8.0% of patients in the 70-mg group and 3.2% of patients in the 140-mg group), one of whom, in the 70-mg erenumab group, tested positive for neutralizing antibodies (0.2%)” (see here under SAFETY)
- In controlled studies with AIMOVIG, the incidence of anti-erenumab-aooe (the main ingredient in Aimovig) antibody development was 6.2% (48/778) in patients receiving AIMOVIG 70 mg once monthly (2 of whom had in vitro neutralizing activity) and 2.6% (13/504) in patients receiving AIMOVIG 140 mg once monthly (none of whom had in vitro neutralizing activity). The neutralizing anti-erenumab-aooe antibody positive rate may be underestimated because of limitations of the assay (emphasis added by me)
- Antibody development on the efficacy or safety of AIMOVIG in these patients, the available data are too limited to make definitive conclusions.
- Erenumab-aooe is produced using recombinant DNA technology in Chinese hamster ovary (CHO) cells.
- Erenumab-aooe exhibits non-linear kinetics as a result of binding to the CGRP receptor (something scary).
- The effective half-life of erenumab-aooe is 28 days (ouch! If it harms you, just to get to half the dose you need to wait a month!)
- The carcinogenic potential of erenumab-aooe has not been assessed.
- Genetic toxicology studies of erenumab-aooe have not been conducted.
- Mating studies have not been conducted on erenumab-aooe (may not be safe while pregnant).
Aimovig™— The Efficacy
This is a fascinating part because, while it is believed by most that a clinical trial is always meaningful and honestly reported on, here we have an example of a misleading clinical trial summary. There were three clinical trials, all of them examined the number of migraine-free days gained using Aimovig™ compared with taking a placebo. The label, which lists all clinical trial details, chooses to ignore a few important factors. For example, they report reduction in migraine days for only those subjects for whom Aimovig™ provided reduction, yet in the three studies, not one exceeded 50%–meaning it did nothing for at least 50% of the participants. In the tables below where the reduction of migraine days is listed, it is only for those for whom the drug actually provided some benefits. It is important to note that in all of the three trials, migraineurs were able to use additional pain reduction agents on migraine pain days, clouding the information gained from Aimovig™’s usefulness or lack thereof. Here is a summary write-up for episodic migraine sufferers participating in the trial:
Between the start of the study and four to six months of treatment, in the 70-mg group, 43.3 percent of patients experienced at least a 50 percent reduction in the number of migraine days experienced each month.
Between the start of the study and four to six months of treatment, in the 140-mg group, 50 percent of patients experienced at least a 50 percent reduction in the number of migraine days experienced each month.
Between the start of the study and four to six months of treatment, in those receiving placebo, 26.6 percent experienced at least a 50 percent reduction in the number of migraine days experienced each month.
The number of days in which patients had to use specific medications to treat acute migraines was decreased by 1.1 days in the 70-mg group and 1.6 days in the 140-mg group as compared with 0.2 days in the placebo group (here)
Let’s examine the reports on the clinical trials—both episodic and chronic migraines, with or without aura. The first and second groups are episodic migraines, where episodic migraine is defined as <15 migraine days a month. These were randomized, multi-center, placebo-controlled, double-blind studies—the first one was for 6 months. Only 90% of those enrolled completed study 1. There are two treatment groups, one receiving one 70 mg injection once a month and the other receiving one 140 mg dose of injection once a month, and a third is placebo group.
They evaluated the success (called “end points”) after 4 months of Aimovig™ use for the three-month period from 4 – 6 months. The findings are as follows:
Let me explain the bolded areas. The 56.7% at the 70 mg dose and 50% at the 140 mg dose represent the non-responding population that took Aimovig™ and had no benefits from the drug at all. Thus, the number of migraine-free days gained (number of migraine-days reduced) represents only those for whom Aimovig™ actually worked. And what was that difference? Less than two migraine-free days compared with the placebo. Given the definition of episodic migraine as <15 pain days a month, saving 1.4 days of pain day for 43.3% of the population means the migraineur still ends up with 12.6 migraine days for a person with normally 14 migraine pain days a month, and for those receiving the 140 mg dose, the reduction is 1.9 days so from 14 days they reduce to 12.1 migraine pain days. This is a rather modest decrease in migraine pain days of 4% for those in the 70 mg group and 6% for those in the 140 mg.
In study 2, a randomized, multi-center, 3-month, placebo controlled, double-blinded study with episodic migraine—very similar to the previous trial with only a dose of 70 mg once a month, patients were also allowed to use other medicines, like triptans when they had migraines. Here 95% of the participants completed the study.
|Migraine-free days gained||Aimovig™ 70 mg||Placebo|
|Change from baseline||-2.9||-1.8|
|Difference from placebo||-1.0 (rounding on label and not by me)|
Note here the responders were even fewer, meaning only 39.7% of the subject received any benefit from Aimovig™, and only gained 1 pain-free day compared with placebo. Given that the definition of episodic migraine is <15 pain days a month, saving 1 day for 39.7% of the population amounts to a 2.65% benefit. A very modest decrease in pain days since the number of pain-days remain at 13 for a person with an average of 14 pain-days a month.
The third clinical trial was with chronic migraineurs, which is defined as >15 pain days a month.
In the chronic migraine group we find the least number of responders. While the migraine-day reduction is 2.5 compared with the placebo, we must remember that in chronic migraine, the pain days are greater than 15. Assuming 16 pain days to be more than fair, saving 2.5 days a month for 39.9% of the population in the 70 mg group amounts to 12.5 migraine-pain days still left and thus the total benefit is 6%, and for those on 140 mg the benefit amounts to 6.4%. Of course, these benefits drop as pain days increase. For a migraineur with 20 pain days, these benefits drop to 5% because she still only gains 2.5 migraine-free days, while the actual migraine-days remain high at 17.5 days. This sort of benefit is of no benefit at all.
Aimovig™ Or Salt?
Given how incredibly little benefits Aimovig™ provides to less than 50% of migraineurs, and with so many unknowns about the possible adverse effects with long-term use, I must wonder: would I ever consider taking a drug like this?
As a migraine sufferer myself, I can reach complete migraine-free status by adjusting what I eat and by increasing my salt consumption. I would never ever consider a drug like this.
Do I need my doctor’s permission to increase my salt intake, as suggested by the Daily Mail? I don’t think my doctor would be very happy if I contacted him every time I used my salt shaker for more salt. Besides, I have increased my salt consumption to be several times greater than the USDA recommendation and while I certainly have no migraines, my blood pressure has never increased either. Salt doesn’t increase blood pressure and for most people there are no risks associated with consuming salt.
Taking any medication always carries the risk of side effects and interactions. Given the miniscule benefits of Aimovig™ as outlined above and the availability of a proven, non-medicinal treatment for migraines, is the enthusiasm for this drug warranted by the facts? What do you think?
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This article was published originally on August 8, 2018.