It’s only been a month – but what a month it has been for Liz. Liz hasn’t had the easiest time of it health-wise. A longtime migraineur and fibromyalgia patient, Liz has had to endure a bucketload of mostly immune health problems that have probably stemmed from a systemic autoimmune disease. They’ve included gastroparesis (age 25), psoriasis (age 27), rheumatoid arthritis (age 29), fibromyalgia (age 36), etc., and then to top it all off, she had breast cancer at 42.
Migraines, though, were her first debilitating condition. They showed up when she was 17 (she’s now 45). For the first 20 years, the ocular migraines – with aura and only a little pain – weren’t so bad. She could take a Tylenol and close her eyes for 20 minutes and be okay.
Around the age of 35, though, she began to have full-fledged migraines – light sensitivity, excruciating pain, nausea, vomiting, etc. – and developed fibromyalgia at the same time to boot.
Over the past nine years, both the migraines and her fibromyalgia have gotten progressively worse and made her life a living hell. As time went on, more and more things could trigger a fibromyalgia flare or migraine. Cleaning (especially utilizing her arms a lot, like folding laundry, washing dishes and vacuuming), most exercise, shopping (carrying heavy bags, going through racks of clothes, and especially the process of shoe shopping), walking in the wrong shoes (she wears tennis shoes most days), sitting in the wrong chair (she has a recliner and that is pretty much the only place in her house she can sit for any length of time – and she would still get a migraine from sitting too long), certain foods, alcohol, smells, light, and the list goes on.
Often her fibromyalgia symptoms would start first – the wide-spread pain and tenderness, usually in her upper back, upper arms, shoulders and neck, her skin that felt tender to the touch and sometimes on fire. Then it would move into her head. It felt like she could feel the inflammation, blood vessel dilation, and finally the irritation of her trigeminal nerve progress to a migraine.
She’s thrown everything she could at them: cold packs, heat packs, a Cefaly device (tens unit for the forehead), Advil, Tylenol, cold sprays, antidepressants, topamax, gabapentin, mild muscle relaxers, clonazapam, massage, acupuncture, chiropractics, trigger point injections with lidocaine (the latter four, unfortunately, turned out to be triggers for her Fibro).
(She found out during her cancer that she has a genetic mutation (on the P450 CYP2D6 pathway) that prevents her from metabolizing many of these medications, which could well explain why the other preventative medications haven’t worked for her.)
Her only relief during the last 8 of 9 years was a triptan drug called Relpax which she could only take twice a week or risk rebound headaches – and her insurance didn’t even cover enough pills for that. Over time as Relpax began to lose its efficacy, the migraines began lasting longer and longer.
She’d reached her wits end. Even her neurologist had given up on her. This year, after switching neurologists, though, her new doctor suggested one of the new CGRP inhibiting drugs – Ajovy (Aimovig or Emgality are also available and another new one will be out soon).
In the 39 days since starting Ajovy, she’s had but a single slight migraine and, get this, no fibro flares since then. Her triggers: shopping, cleaning (a LOT of cleaning), alcohol (!) – are not triggering. She has more energy, her sleep has improved, she has less brain fog and cognitive dysfunction and more mental clarity. She hoped the drug would work for her migraines but got an extra bonus when her fibromyalgia symptoms subsided as well. She said,
“I feel like I have my miracle! 9 years of chronic migraines and Fibro with nothing working – during such an important time in my kids’ lives. I felt like a horrible mother and wife. I had a hard time cooking and cleaning. My husband would have to pick up the slack when my kids were still little. I’d have to go hole up in a dark room and hope to sleep it off. I can’t tell you how close I was to just giving up. The pain just made me bitter, grumpy, and I felt useless. It affected every aspect of my life, and my husband and kids were resentful (as if I could help it – the cancer was like adding insult to injury).”
She will be taking one shot every four weeks. She has had several other friends who have had success on this medication, or others in this class, and they still have a couple of migraines a month. For some the drug doesn’t work at all, for others – about half – it cuts their migraines in half, for some it cuts them by 75% or more. With her almost total reduction of migraines and fibro-flares, she appears to be something of a super-responder.
She stated, “I really do hope this line of immunology drugs are the answer for so many with chronic pain conditions, like migraine, FM, ME/CFS, Trigeminal Neuralgia, MS, etc.”
She has reason to be optimistic regarding the power of this line of next-generation immunological drugs. Liz had a form of breast cancer called HER2 positive, which was treated (in addition to surgery and chemo) with monoclonal antibody drugs called Herceptin and Perjeta.
Those new drugs may have saved her life. Survival rates for HER2 positive breast cancer prior to the introduction of the new monoclonal antibody drugs was just over 50%. Now it’s up to 95%.
Noting that, “these new migraine meds are also made from monoclonal antibodies,” this is her second big success with a monoclonal antibody drug. Just as the Herceptin blocked the HER2, the new migraine drugs block the CGRP receptors. She said, “It truly fascinated me that these meds can manipulate these antibodies to target specific proteins! It’s wonderful that another immunology drug made from monoclonal antibodies is saving my life once again because I truly felt that migraine disease and fibromyalgia were even worse than my cancer!”
A Fibromyalgia Connection?
Perhaps the best question to ask about the drug’s success with Liz’s fibromyalgia is not why it happened but why would it not? The two diseases, after all, seem to be inextricably linked and the protein the drug is targeting may be key to hypersensitive pain states.
One large study (n=1700) found that no less than 56% of fibromyalgia patients met the criteria for migraine, and that the “penalty” for having both conditions was steep indeed. Women with FM and migraines were more prone to having a variety of other ailments including hypertension (p<.004), asthma (p<.01), irritable bowel syndrome (p<.02), depression (p<.0002), anxiety ( p<.001), PTSD (p<.005) and finally (and most of all) chronic fatigue syndrome (p<.0001).
In fact, the whole constellation of diseases associated with ME/CFS and FM (GWI, postural orthostatic tachycardia syndrome (POTS), IBS) appear to share an increased prevalence of migraine. Migraine, ME/CFS, FM and irritable bowel syndrome are among the eight pain conditions a 2015 NIH report proposed “share common underlying disease mechanisms”.
The new migraine drugs target a protein called Calcitonin Gene-Related Peptide (CGRP) found in nerves and blood vessels which appears to play a key factor in the development of both peripheral and central sensitization as well as inflammatory and neuropathic pain.
In migraine, ME/CFS and FM, exertion and exposure to stimuli often must be curtailed dramatically. Whether in the midst of an ME/CFS crash, fibro flare or migraine attack, hypersensitivity to lights, sounds and odors are common. The following description of a migraineur’s brain sounds very much like an FM, ME/CFS, or multiple chemical sensitivity patient’s brain.
“A migraineur’s brain is like a car with a heightened alarm system that ‘goes off simply because you walked close to it.’ In the end, the brain reaches what Sigal describes as a ‘permissive’ state, in which normal light becomes very bright, normal sounds very loud, ‘and you can smell a perfume two blocks away from Bloomingdale’s.’ CGRP-binding antibodies help turn down the volume in the trigeminal nerve, by ‘mopping up’ excess peptide or preventing it from binding to and activating cells…” Underwood -ScienceMag
Baraniuk and Rayhan have even suggested that a migraine-like model may apply to ME/CFS. They propose that the more short-lived cortical spreading depression (CSD) found in migraine – which results in hypoxic conditions and an emphasis on anaerobic metabolism – may have become chronic in ME/CFS.
The anti-CGRP drugs inhibit the sensory neurons in the trigeminal system from releasing CGRP. The trigeminal nerve, the largest and most complex in the head, regulates sensations in the head, neck, sinuses and jaw. Nerve activation in the trigeminal vascular system – which, interestingly, originates in the brain stem – can result in CGRP release, vasodilation (blood vessel swelling) and mast cell degranulation (inflammation)…and migraines.
Since CGRP is also found in other areas of the brain and spine known to be affected in FM, one wonders if the new drugs could affect those areas.
The new drugs may not be easy to get. Insurance companies will probably require the failure of two less expensive migraine drugs before they will cover the $7,000 a year or so the new drugs cost. Whether or not the new migraine drugs will work in FM, their introduction has buoyed researchers attempting to understand and treat chronic pain. Hopefully, studies will begin assessing CGRP levels in fibromyalgia.
Michael Moskowitz MD of Harvard believes that a successful run of anti-CGRP drugs will cause drug companies to ramp up their efforts to deliver treatments for diseases like fibromyalgia. They may very well do so in conjunction with the HEAL Initiative – an NIH funded public-private enterprise which aims to bring new pain-relieving drugs to the fore.
Note that migraine is greatly underdiagnosed and you could be experiencing migraines without knowing it – and possibly missing out on a new generation of drugs which may help relieve your pain.
Find out more about headaches and migraine in ME/CFS and FM.