This is a new letter to the editor that I wrote, in the journal Headache; these newer CGRP meds are marvelous for many patients, but the true side effect profile is just evolving:
(LETTER FROM THE JOURNAL HEADACHE, JULY, 2019: LAWRENCE ROBBINS,M.D.)
Erenumab, the first of the calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) for preventing migraine, is usually referred to as “safe.” 1 Panels of physician experts often minimize the side effects. Our literature is replete with descriptions of the mAb studies, which resulted in almost no adverse events. 2-4 The other CGRP monoclonal antibodies (fremanezumab, galcanezumab, and eptinezumab [awaiting Food and Drug Administration (FDA) approval]) are also widely regarded as having minimal side effects. However, the “real world” experience with erenumab is quite different. As of March 31, 2019, the FDA Adverse Events Reporting System Public Dashboard listed 10,531 total adverse events for erenumab. Of these, 1460 were considered serious – some life threatening. This was after only 10 months of use. These high numbers eclipse those listed for onabotulinumtoxinA. For all uses, adverse events reported for onabotulinumtoxinA totaled 33,372 between 2002 and 2018, an average of 2086 events per year. We are only discussing short-term problems due to erenumab. Long-term side effects remain largely unknown.
This author has personally communicated with many “high prescribing” headache providers regarding their experience with erenumab. Most feel that constipation is a common occurrence. For some erenumab patients, the constipation greatly diminishes quality of life. Very few of these high prescribers officially report the “mild or annoying” adverse events. Many have encountered at least one serious side effect. To be fair, there are headache providers who state that they rarely hear of any side effects.
My patients have reported a plethora of side effects. 5 Constipation has occurred in 20% of these patients. Other side effects encountered have been nausea (7%), worsening headache (5%), fatigue (5%), depression (3%), and joint pain (3%).
Four of our patients have experienced a serious side effect that was likely related to erenumab. These 4 include: A 31?year?old woman with severe neurologic symptoms, including hemiparesis. She also suffered from severe fatigue and joint pain. Her work-up was negative, and she slowly recovered; a 21 year old woman, with a history of hemiplegic migraine (no events since 2015), who suffered a probable migraine?related stroke. She reported dysgraphia, which has improved by 80% over 6 months; a 65 year old woman with a history of rheumatoid arthritis, who reported suffering from severe fatigue and joint pains, which eventually resolved on Prednisone; and a 60 year old woman with reversible cerebral vasoconstriction syndrome, which resolved without a cerebral infarction.
I have monitored various online patient migraine chat boards. Many of the patients have experienced an excellent response to erenumab. However, a significant percentage of patients describe mild or moderate side effects with erenumab. Severe adverse events are also commonly reported. It is generally accepted that online patient reports are not always reliable. Even still, when I compare the online patient comments regarding erenumab to those of onabotulinumtoxinA, there is significantly less reporting of side effects from the onabotulinumtoxinA. This matches my clinical experience.
There are many theoretical risks from blocking CGRP. 6-10 Evolution has deemed CGRP to be an important substance in virtually every organ system. In the limited number of patients studied, the use of erenumab over a number of years has not resulted in long-term adverse effects. However, we will only know about long?term effects in 10-20 years.
The CGRP mAbs have not been studied in patients who are under significant stress. During stress, CGRP plays vital roles. CGRP also is located in the pituitary and hypothalamus. The blood brain barrier does not protect these areas from mAb penetration. Before testing these antibodies in adolescents, hormonal studies should be accomplished.
Using the available information, I would “guesstimate” that the risk for a serious adverse event is approximately 0.5% of patients. It appears as if most of these serious events resolve over time. The “non-serious” side effects, such as constipation or worsening headache, are often disturbing to a patient’s quality of life. This letter focuses on erenumab, which was the first mAb on the market. It is too early to assess risk from the other mAbs.
When we discuss risks vs benefits, patients deserve more than to hear “it is very safe.” We should include the possibility, although remote, of incurring a serious side effect. Erenumab has been life changing for tens of thousands of migraineurs. I am grateful to the companies for bringing these to market. With that, we must be open with our patients about the possibility of side effects.
Well said.
Thank you. Now to communicate this with practitioners.
As always thank you Dr. Robbins. Your article brought to light the under-reported side effects that in a particular patient may be unacceptable; the trade off not beneficial enough. For me my stress level is one variable that directly correlates to my migraine frequency & every day pain level. The risk of this being thrown off — even just for a few days / weeks — would take me months to correct. In addition I admire your non-alarmist perspective & your positive support for the many migraineurs who have benefited!
thanks Ross…..LR
Thank you, Dr. Robbins for this article and for being proactive. I was prescribed Aimovig 140mg for my chronic intractable migraines with aura. I was told there were two side effects, both minor- constipation and injection site irritation. Because migraine with aura does involve some degree of increased risk of stroke and because my migraines were 30 days per month and because side effects were so minor, I agreed to try Aimovig. Eleven days after dose 1, I vomited for nearly 5 hours from a migraine. I hadn’t vomited as a result of migraine since I began Verapamil as preventive several years prior. In fact, Verapamil decreased the severity of the migraine headaches and fully stopped my migraine vomiting. I took one more 140mg Aimovig dose in January 2019. I have been suffering every single day since and am wondering if I developed an immune response. Injection site stinging pain (the pain experienced not when the needle went into the skin but, instead when Aimovig was distributed into my thighs) remains 24/7/365 since then. My legs buckle at times when I walk or stand. Shortness of breath is extreme including when I brush my teeth. I have seen a cardiologist and a pulmonary specialist and have many tests run. Both doctors believe Aimovig is the reason for the shortness of breath. This is based on examination and test results combined with understanding of CGRP and its role within the affected systems. My Raynaud’s has worsened, I developed ance (acne took a couple of months to resolve with the use of Retin-a), I developed GERD and sharp pains in the stomach organ after 2 doses of Advil. Given ibuprofen and its impact as a Cox 1and 2 inhibitor and the role of CGRP within the stomach, my GP told me to take Nexium and to try to avoid Advil. He acknowledged that some of my migraines were so severe that I had to take Advil to reestablish my peripheral vision due to migraine. My GP was frustrated that there is nothing listed about risk of combining Aimovig and ibuprofen. I have joint pain and stiffness which makes bending and then straightening difficult and painful. Nausea is very, very frequent and I was prescribed Zofran to be taken at onset of that severe nausea that now occurs every time a migraine is triggered by barometric pressure changes and/or rain. I have had 9 migraine episodes in which vomiting couldn’t be prevented with each episode lasting at least 3.5 hours. Nonstop. I have had to relearn migraine symptoms. Whereas in the past, for the 40+ years I’ve had migraines, eye twitching and face and fingertip numbness meant I’d have an aura, those now precede every migraine that causes violent nausea. Zofran is always with me both in my nightstand and in my purse. I have very loud tinnitus in my right ear. I saw an ENT about it. He noticed that my balance was also off. I told him that Aimovig was in my system. He asked if the balance problem and tinnitus both began after the doses of Aimovg and I answered that they had. I developed constipation that lasts up to 3 days, non-migraine headaches, non-cardiac chest pain, EXTREMELY painful muscle spasms in my upper abdomen, mid back, upper trapezius muscles and my thighs. In case it’s relevant, Aimovig was only injected into my thighs, not into my abdomen or upper arms. The muscle spasms in my abdomen produce so much pain, put pressure on my stomach provoking non-migraine nausea. I have noticed that wounds take longer to heal and they don’t heal the same (I have a picture of a minor wound on my finger – no scab formed on most of it, the skin didn’t come back together of the top layers for more than a week and a half). I have had significant hair loss with chunks of my hair coming out into my hands in the shower. Chunks. There are several very thin areas on my head. My quality of life is worse than it was prior to Aimovig. I didn’t think anything could get worse than chronic intractable migraines but this is awful. I can’t walk my dog more than one block, I hold onto the counter while brushing my teeth and loading the dishwasher because I become winded, the muscle spasms hurt so bad, the tinnitus is so loud that I always have background noise or I can’t sleep. The nausea has made me fearful to go anywhere because onset is so fast. Worst of all, I don’t know if or when this will stop or if any of this is permanent and that’s causing fear, anxiety and depression. I am having bloodwork soon to look for a specific immune response. I would gladly have back my old nonstop migraines. The following is unrelated to my side effects but, it might be relevant: I had multiple rounds of Botox years before I was prescribed Aimovig. I did well at 200 units Botox in that it fully stopped all migraine headaches for 2 months after each dose. However, it didn’t prevent my other migraine symptoms. My insurance changed and would only cover 30% of Botox making it unaffordable. The insurance company did add Aimovig to its formulary with out of pocket of $100. For some reason that the insurance company will not share with me, it now refuses to cover Aimovig but does cover the competing CGRP antagonists.
Thank you for sharing…these drugs can be great, but have serious possible side effects…..
Thank you for your thorough explanation. I too have daily migraines. After reading this, it made me realize that I know what I have now and it is tempting to try something else, but now I am afraid. And rightfully so. I also have tinnitus. And joint and muscle pain. I gave up wine drinking and now Im walking much better. Hils were so painful I could barely walk some days. I take Maxalt 10 mg everyday and some days 2 pills.
Did your back pain get better over time?
It’s about 4:30A and I’m up thanks to core spasms. They are incredibly painful. Beyond the pain, I’m afraid because I’m now more than 2 years since my final dose. My injection sites in my thighs also continue to sting on a daily basis. Additionally, the nausea that began to occur with most of my migraines while on Aimovig also remains. I had to take two doses of Zofran yesterday. This is one of the most upsetting aspects. Prior to Aimovig, I hadn’t had nausea due to my migraines for more than ten years. Verapamil controlled that as well as reduced the frequency of excruciating migraine headaches. My doctor increased my Verapamil since Aimovig with the hope that the higher dose would again bring the nausea under control. But it hasn’t. I am angry that the migraines are worse. If Aimovig didn’t do anything I’d consider it a pricey lesson. But the fact that it made my migraines worse and continues to cause core spasms and stinging injection site pain is unbearable. I don’t set foot outside if it’s raining, snowing or a storm is on the way because I know that almost immediately I’ll become nauseated from an instant onset migraine. I’ve become anxious and fearful of the nausea and the muscle spasms. The pain in my upper abdomen and around to my back during the spasms feels like my ribs are being crushed. I’m very afraid that I’m more than two years out since my last dose because what if this is permanent? The newer Aimovig commercials mention muscle pain. That doesn’t begin to describe what I experience. You can actually see my upper abdominal muscles twitching and my mom and doctor have both felt the spasms by putting their hands on my stomach. I sat in the exam room, writhing in pain and they agreed that it felt like the muscle contractions a woman experiences lower on her abdomen during labor. I can’t possibly do more than beg people to please look at the company study report – not the prescribing info. It is unbelievably unethical not to list in the prescribing information all the side effects experienced by people in the study. They note that they chose not to include side effects if the difference between placebo and the 70mg and 140mg doses were less than a certain percentage point. But, they have no qualms calling the doses successful with so little difference between both 70mg and 140mg against placebo. That aspect is also frustrating. Every time Aimovig and the other meds in the category were discussed on news reports, they were referred to as ‘game changers’ for the millions of Americans who suffer migraines that aren’t well controlled by other classes of medications. But the data itself doesn’t bear that out. Patients and insurance companies are paying a lot for meds that, at the higher dose, only beat placebo by about 2 days. So, for example, a test patient might experience 4 fewer migraine days per month on placebo and 6 fewer migraine days per month of 140mg. The overall benefit is 2 days compared to placebo. Is that worth the financial cost and the risk of long term debilitating side effects? I belong to an online private migraine support group. One woman has now injected herself 8 times with 140mg Aimovig and is experiencing side effects, has no migraine control during her period, no migraine control when she’s under stress and no migraine control when the weather is bad. But she’s invested a lot of money in copays and a lot of hope so she’s not ready to say the medication has failed her. I no longer ask her to please rethink what she’s doing. But the others in the group have had similar experiences that I have and all discontinued as well. Some opted to try the competitor meds hoping they might work better with fewer side effects. A few have reported back that those meds work a little better for them. The rest stopped the competitor meds as well. Migraines are complex. I get why blocking CGRP was thought to possibly short circuit the process involved with migraines and I’m sure an enormous amount of money was spent by all the pharmaceutical companies who produce this class of meds. But post-market data across the board most definitely shows that they are not the game-changing wonder meds that they were expected to be; at least not for the vast majority of migraine patients who have been prescribed them. Beyond that, I worry how many people decided to try these meds because they’ve been told that there are only a few side effects. That should defy reason when you think about it. When was the last time you saw a commercial for any prescription medication with only two or three side effects listed? Rant over. It’s past 5 am here and typing while twisted half on my side, half on my back as I try to find a decent position, least painful during these core spasms isn’t working well. I wish you well.
Thank you sincerely for your comments. It disgusts me how devalued patients are and how the almighty dollar reigns supreme. I’ve watched, and pleaded, as not just my own life has been stolen from me, I’ve been subjected to torture over and over, but also the masses who are misfortune enough to trust in the medical system, the government and society as they are sacrificed merely so that others can profit and never admit any folley. Even the atrocious war on drugs has been obfuscated in such a way so that the public wouldn’t ever figure out that the government, medical system and society are responsible for the “epidemic”, for the death toll ballooning to ten times what it was before war against people. Drugs are inanimate; they don’t fight. And in fact the deaths being attributed to drugs are largely due to the stress of the war. Without the war, there wouldn’t have been the deaths and overdoses, accidental or intentional. That’s not to say that truthful education isn’t necessary. But everything is slanted and spun to create a villain and feed an agenda rather than tell the truth.
I believe that one of the ways to help straighten out these injustices is to create a patient lobby group to represent patients rights and voices in government. I rarely have the capability to even write or communicate, but somehow, some way, eventually, I need to find a way to make this happen if we are going to make some headway. There are more people affected by chronic illness and/or chronic pain in the community than not. Literally, more than 50% of the population, so we have the numbers. Food for thought.
At the very least, know that I feel for you and recognize that what happened to you happens much more than even you realize. I don’t want to say too much however.
Load note an top-level stakes seeking your team. chicagoheadacheclinic.com
http://bit.ly/2NLzKM8
Last fall, my doctor told me about Emgality. I decided, because I was told there were very FEW and mild side effects, to try the shots.
My 1st month was great. For the first time in years I had only two to three migraines that month! I was ECSTATIC. Though the medicine wore off by the 3rd week, I agreed with the NP whom I saw at my next appointment to continue with the med, with the hope that building it up in my system would be the most beneficial, since I had such positive results.
I cannot tell you how much I’ve regretted this decision after 4 shots! I began experiencing a variety of symptoms that I did not connect to the medicine until later, after reading patient reviews online. That was my ah-ha moment.
This medicine has destroyed my life.
OVERWHELMING fatigue, sleeping up to 20 hours a day.
My chest feels funny; not pain exactly, but not normal, either. Rather a heaviness of sorts. Constant sore throat.
I have hot and cold flashes. (The hot flashes are not just flushing; they are me dripping sweat).
My neck and head hurt so badly I pray to just die and get it over with. It’s the worse pressure I’ve ever felt, 24/7. I’ll take migraines any day over this.
Extreme pain in my left shoulder (to where I can barely lift my arm), as well as my left knee, (I have difficulty lifting my foot, thus difficulty walking). I’ve NEVER had joint pain before. I’m also very off balance at times. My thoughts became increasingly confused and DEPRESSIVE, though the confusion is resolving, slowly. (I’m normally very optimistic. I am still depressed, but I logically attribute this to the cgrp effect on my brain.
I’ve lost my appetite, and despite forcing myself to eat, usually under 1k calories most days, I’ve gained over 20lbs.
These are my major symptoms, though i have had some uti’s and developed persistent, loud ringing in my ears.
I do know my doctor reported only TWO symptoms to FDA, though I’ve described them all to him.
I only pray this medicine’s effects wear off soon. I literally feel like I am slowly dying. I understand from my research there is a 5 -6 month half-life with these meds. After a 3 month trial, ending this past Jan, I am still suffering severe side effects in May. I am back on triptans, which help to ease the now constant headache.
At the very LEAST the FDA needs to update their pamphlet info on these drugs, including ALL the detrimental reported side effects.
I am sorry to hear, these are very serious side effects; the initial studies did not identify these, and now we are discovering…..
I am just 2 weeks past my first injection and I’m too exhausted to get out of bed. I have fibromyalgia but in all the years I’ve had it I have always been able to get up. Now that I look back, I realize that the muscle cramps I started to experience when walking within days of the injection were a side effect of this drug. I thought I had just gotten too little exercise. My muscle and joint pain are increasing daily. The muscles in my chest are tight making me feel short of breath. I’ve had no constipation. I’ve started having bizarre dreams and angry outbursts. I have tremendous regret for taking this medication. Suffering from fibromyalgia I should have been more wary that I would be more likely to have my symptoms worsened. All I can hope is that the side effects start reducing as the weeks go by. I wish the half-life was much, much shorter.
I get severe Cluster headaches, was looking forward to these injections but a little wary,Injections worth a months Meds sound scary to me if you have a reaction then you are stuck with an overload of it in your system, for that reason I was gonna try the oral CGRP first to test it out and would hope any smart Doc would start it slow that way, for me ambien works wonders since my clusters are nighttime occurence,however my Doc acts like Ambien is the bigger evil compared to CGRP blockers, I am trying to follow my gut instinct and wait out for more research.
yes these mAbs could help clusters BUT they do carry the risk of side effects, much much more than were revealed in the official studies; and Ambien is ok, its just that we try other, non-habit forming meds first; and of course the “Sleep Rules” outside of the meds….
I was so ecstatic that Aimovig took my chronic migraines from 20 per mo to -0-. But noticed during the 8 mo since I began injecting that I still have the visual aura, just no pain a couple times a month. However, I paid this no mind since I had no pain. Then the 27th of Jan after my 8th injection I had 4 auras in just 5 days. On the 6th day I was rushed to the hospital with (my first ever) seizure. It was serious and they kept me overnight. They were sure I’d had a stroke. I did not. Thankfully it was only the seizure but it was serious enough that I’m now on Keppra and can’t drive for 6 months! I’m 66, I’ve had these migraines for 52 years. The only thing that changed is Aimovig. I can’t help but think, with the auras, and the addition of the Aimovig that it had something to do with the new onset focal seizures. Anyone else?
yes there are many many side effects that are occurring, and patients need to be aware….
Thank you to all for your input. I’m a 62 yr old woman who has suffered with migraines most of my life. Have tried everything without much relief. Neurologist suggested Aimovig 3 months ago. First 2 months felt like I had my life back. Noticed the last week before next injection would start getting migraine, not as severe. After 3rd injection, started aching next day, severe fatigue, sore throat, extreme heaviness in my chest, joint pain, pain in shoulder. I’m an asthmatic. Got to where my inhalers had no effect. Began to think I had COVID-19. Ended up in ER. Thank goodness no Covid-19. But left with no real answers why, other than asthma. Had to use nebulizer several times a day. Finally, feeling better. Have really been perplexed as to what caused this. After reading this, I don’t think I will be using Aimovig in the future. Dread the migraines, but think I can deal with that better than not being able to breathe. Migraine sufferers need to know what the potential side effects are before deciding to take this. I’d be interested in knowing if any asthmatics have experienced similar symptoms.
yes, the side effects are many(as of Dec31, 2020, 41,000 side effects reported to the FDA, 5,500 serious ones); patients should know, but the problem is doctors are not aware; the PI needs to be updated…..Larry Robbins
I took this “no side effects at all” for 8 months. Twice I became so constipated I thought I had to go to the ER. I had no idea this was drug induced. I have had GERD for years and some loose stools with dairy and salads or food poisoning. But never constipation My loose bowels stopped immediately after taking this drug by injection and I wondered what was up with that. But no side effects both my Neuro and intern said. After the second episode I started to read. Colons taken out, esophagus not working, that was enough. I stopped. I also had whispering bowels or whistling which is a sign of blockage. I thought it was a new pillow as I could not localize the noise. After stopping I had another episode shortly after and ended up at the ER. This is a dangerous drug and unnecessary, At 9600 a year for life it is obviously a big money maker. Try triptans and narcotics. They work for about 65 a year. Take them and nap and 90 percent will be fine.
these monoclonals have alot of adverse effects; as of 12/20, there were 41000 side effects reported to the FDA, 5,500 serious ones; this is not unique to these monoclonals; many drugs come out with a relatively clean PI, only to have thousands of adverse events reported a year or two later; we have to change, mostly thru the FDA, how side effects are aquired in clinial trials….
I have been on Emgality for 2 months. My migraines are much fewer and less severe but I have developed constant and intense acid reflux. Besides briefly during pregnancy, I have never had acid reflux before taking Emgality.
It may or may not be the Emgality; I would definitely suggest consulting a GI doctor….Emgality does, as with the other mAbs, result in a plethora of side effects…..