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CGRP Drug for Chronic Migraine: Very Promising Study Results

cgrp-drug-for-chronic-migraineAmgen’s CGRP drug provided significant relief to participants with chronic migraine, according to new study results presented at an international conference in mid-September. The drug, called erenumab, was tested at two doses, 70 mg and 140 mg. “Both doses of erenumab were associated with significant improvements in health-related quality of life, headache impact, disability, and level of pain interference, compared to placebo,” according to Amgen’s press release announcing the study’s results.

Here’s a brief summary of the study’s details and it’s findings.

In the 12-week study, 667 participants were given monthly injections of either the drug, called erenumab, or a placebo. The breakdown was:

  • 191 participants received 70 mg erenumab
  • 190 participants received 140 mg erenumab
  • 286 were injected with the placebo

All participants had chronic migraine. At the start of the study, they had an average of 18 migraine days per month and 21.1 headache days each month. The following outcomes were assessed during the last four weeks of the study.

  • Reduction in migraine days per month: Those who were given erenumab (at either dose) had an average of 6.6 fewer migraine days a month.
  • 50% or greater reduction in the number of migraine days per month: 40% of participants who received the drug at 70 mg and 41% who got 140 mg had their number of headache days decreased by at least half.
  • Reduction in use of acute migraine drugs (abortives): Participants who received 70 mg of erenumab took abortives on 3.5 fewer days; those who received 140 mg reduced their medication use by 4.1 days.
  • Reduction in headache hours: Participants who received 70 mg of erenumab had 64.8 fewer headache hours in the month; those who received 140 mg of erenumab had 74.5 fewer headache hours.

Side effects

No adverse effect was reported in more than 5% of the participants. Those reported were:

  • Injection site pain: 3.7% in participants who received the active drug at either dose; 1.1% placebo
  • Upper respiratory tract infection: 2.6% at 70 mg; 3.7% at 140 mg; 1.4% placebo
  • Nausea: 2.1% 70 mg; 3.2% 140 mg; 2.5% placebo

This yet is another promising report on the CGRP drugs that are in development for migraine prevention. All studies so far have found a notable reduction in migraine frequency and improvement in health-related quality of life for a significant portion of participants. Minimal side effects have been reported thus far. This was a Phase 2 study. Phase 3 studies, which are underway now, will include more participants and give us more information on side effects.

(Amgen has also issued a press release about the first CGRP drug Phase 3 results I’ve seen. Participants in the study had between four and 14 migraine days a month. Those given erenumab had an average of 2.9 fewer migraine days per month. With such a wide range in migraine frequency, it’s hard to tell how impressive that number is. But even for someone with 14 migraine days a month, the average would mean about 20% fewer migraine days.)

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Migraine and Stroke, Heart Disease: Understanding the Risks

Learning that research has found connections between migraine and stroke and heart disease can be chilling. Fortunately, the news is not as bad as it might first appear. I spoke with headache specialist Gretchen Tietjen, M.D., about an article on the connection between migraine and an increased risk of stroke and cardiovascular disease that she wrote for the American Migraine Foundation. “From a patient’s perspective, this information is frightening,” I told her (because I have no poker face, even on the telephone). Dr. Tietjen soothed my worries tremendously by putting the information into perspective.

“It can be very scary when you read things like this,” Dr. Tietjen said. “Study after study shows this little bit of increase.” However, the risk is very small. The most important takeaway is that patients should keep migraine in mind as part of their overall risk for stroke and heart disease. If you have migraine and are at increased risk of stroke or heart disease, it’s extra important to be aware of and manage those risk factors.

Migraine Increases the Risk of Stroke and Cardiovascular Diesease (But Only a Little Bit)

Yes, migraine does increase the risk of stroke, particularly for women who have migraine with aura. But the risk is very, very small. Less than 1% of all strokes in women have any connection to migraine. And the presence of a connection is not proof of a causal relationship—that is, just because the two are linked doesn’t mean that migraine causes stroke.

The article reports that a recent study found “that migraine increases the risk of stroke, coronary events, and related death by about 50%.” At first glance, that sounds terrifying, but Dr. Tietjen’s clarification was soothing. She said, “This sounds worrisome but to put this in perspective only 1% of the total population in the study had a cardiovascular event over the 20 years of follow-up. The take home message is that having migraine does not mean you will have heart disease or a stroke, only that it appears to slightly increase the risk.”

Risk Factors For Stroke and Heart Disease

Dr. Tietjen highlighted risk factors like smoking, high blood pressure, high cholesterol, and diabetes. She said that in people with migraine, these factors have an additive effect—the combination of more than one risk factor is worse than any one by itself. If you have any of these risk factors in addition to migraine, quitting smoking, lowering your blood pressure and/or cholesterol, or getting your diabetes under control could lower your risk of heart disease substantially. Smoking is the risk factor that stands out the most to Dr. Tietjen. Studies of migraine and smoking have shown that the combination of the two increases your stroke and heart disease risk more than either one on it’s own.

Learn More About Migraine, Stroke and Heart Disease

Dr. Tietjen’s article, Migraine, Stroke and Heart Disease has in-depth information on who is at increased risk of stroke, differentiating between symptoms of migraine and stroke, the physiological links between migraine and stroke, and ways to lower your risk. As you read the article, keep in mind that the absolute risk is small and that you can modify your risk factors for stroke and heart disease. And make a list of any questions you may have so you can ask your doctor at your next appointment.

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Miles for Migraine Raises Awareness, Research Funding

Miles for Migraine logoThrough Headache on the Hill, patients and healthcare providers lobby members of Congress each year to increase NIH funding for research into headache disorders. The first year, participants were told that they would have to raise “big noise” in their own communities to see a change. This is something people who advocate for more research funding hear often: lawmakers must believe that the people they represent care about migraine and other headache disorders. That is, we won’t get research funding until we raise awareness about the impact these illnesses on people’s lives.

Miles for Migraine Raises Awareness, Research Funding

In 2008, Eileen Jones decided to make big noise by founding Miles for Migraine. After attending the first Headache on the Hill in 2007, Eileen, a nurse who has migraine, founded Miles for Migraine to raise both funds for and awareness about migraine. Since the first race in San Francisco, Miles for Migraine has raised $79,000 for migraine research and advocacy. Their goal is to fund 30+ fellowships to train new doctors to become headache specialists. Prior funding recipients include:

Race Locations

That $79,000 is just the start. Last year, the race expanded to Philadelphia; this year, a race has been added in Chicago. Depending on the city, races range from one-mile walks to a full marathon. If you’re unable to participate in or attend a race, you can still get involved through Miles for Migraine’s virtual race.

Virtual Race

When Miles for Migraine comes up, people inevitably say that exercise is a migraine trigger, they’re too sick to exercise, or migraine makes their lives so unpredictable that they’re unlikely to be able to attend an organized event. I get this—all have been true for me at different times in my migraine life—and the people at Miles for Migraine get it, too. That’s where the virtual race comes in. You can recruit others to run for you, collect donations for a run/walk you do on your own (a short trip on the treadmill counts!), or you can fundraise without running at all. All those options raise both awareness of migraine’s impact on people’s lives and money for research and advocacy. Donations of at least $100 will get you a T-shirt and race goody bag. See Miles for Migraine’s virtual race on Crowdrise for more information.

2016 Miles for Migraine Races

  • San Francisco on Sunday, July 31: San Francisco Marathon (Mission Street & The Embarcadero); 5K Walk/Run, Half Marathon, Full Marathon
  • Chicago on Monday, September 5 (Labor Day): Naperville Last Fling (440 W. Aurora Avenue, Naperville, IL 60540); 1 Mile Run, 5K Run
  • Philadelphia on Saturday, October 8: Valley Green/Fairmount Park (120 W. North Western Avenue, Philadelphia, PA 19118); 2 Mile Walk, 5K Run, 10k Run

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Getting into a CGRP Drug Study for Migraine

Getting into a CGRP drug study for migraineThe logistics of finding a CGRP drug study are relatively simple—the hard parts are meeting the study criteria and living close enough (or being able to travel) to a location that needs trial participants.

Finding Clinical Trials

ClinicalTrials.gov is a registry of medical studies around the world. You can search for studies on any condition you’re curious about and can narrow the list by location. It’s the most detailed search, but can be overwhelming.

CenterWatch is another database of clinical trials. You can search studies and research centers by condition and/or geographic location. It has less information than ClinicalTrial.gov, but the format is easier to follow. CenterWatch offers a free email notification service of new trials.

The Center for Information and Study on Clinical Research Participation will search trials for you. Call 1-877-MED HERO or complete the online search request form to receive search results by email in about a week. (The trial search function on the website searches CenterWatch’s database.)

Current CGRP Drug Studies for Migraine

My search for migraine CGRP on ClinicalTrials.gov turned up 29 studies, many of which have already been completed. The ones that are currently recruiting are:

Don’t take this list as the only options—doing your own search with your own terms might turn up something I missed. You can save time by limiting results to the state you live in. New studies are added all the time, so be sure to check back for ones that you might qualify for. Or sign up for CenterWatch’s email alerts.

Study Eligibility

To really know how a drug or treatment works, researchers need to compare similar patients to each other. To do this, they must limit participants by certain eligibility criteria, which vary from one study to the next. Read through a study’s eligibility requirements closely—you may meet all the criteria except one (that’s usually the case for me). Frequency of migraine attack is a major criterion; how many preventives you have tried, drug allergies, recency of Botox injections, or having an uncommon subtype of migraine are some examples of other criteria.

Study Contacts

Depending on the study and where you’re searching, the contact may be a specific doctor or hospital, company that runs clinical trials, or a general contact phone number or email address. If you see the name of the center, but no phone number, Google the name and go from there. I’ve never had a central contact respond to email or phone calls, so I recommend trying every other possible avenue as well.

Talk to your doctor, too. They may know about trials in the area or have information on upcoming studies. This is most likely if you see a headache specialist at an academic headache center, but it’s worth a try even if you don’t.

What You Need to Know About Clinical Trials

Having the option of clinical trials is great for patients who need relief and want to try a new treatment, but they are still experiments. You may get a placebo. You may get the active drug, but at a lower dose than is effective. You may experience side effects that are not yet known. These risks are worth it to some people and not acceptable to others. If you are chosen for a study, ask every question you have and don’t agree to participate unless you are satisfied with the answers. Try to view the risks as objectively as possible to make the most informed decision you can. People can die during drug trials—that’s exceedingly rare and the CGRP drugs have had mild side effects in studies so far—but it’s important to try to keep your eyes wide open. It’s so easy to be blinded by a desire for relief (I speak from experience).

Learn More About Clinical Trials

If you’ve participated in in drug studies and would like to share your experience, please leave a comment or email me at kerrie[at]thedailyheadache[dot]com.

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Migraine Prevention With CGRP Drugs: Cost, Safety

migraine-prevention-cgrpYou’ve probably heard that monoclonal antibodies that inhibit CGRP are the exciting treatment in development for migraine prevention, but details have been scarce. New Migraine Drugs Promise Relief—But at a Steep Price is a different look at the drugs than has been published thus far. I’ve hit some highlights below and added my own thoughts, too.

Migraine Prevention is Costly & Access is Restricted

  • Monoclonal antibodies are made from living cells and are expensive to produce. They are among the most expensive drugs on the market right now.
  • Experts the writer interviewed gave cost estimates of between $8,000 and $20,000 per year. The CEO of Alder BioPharmaceuticals, which is one company working to develop these drugs, compared them to antibodies used to lower cholesterol. Those cost $14,000 a year when they came out. “I suspect we might be in that ballpark,” said Alder’s CEO.
  • Insurance companies tend to restrict drugs with hefty price tags. Think about the hoops people have to jump through for Botox, which costs insurance companies $6,000 to $10,000 per year.
  • Like with Botox, many insurance companies will likely require patients to fail trials of other medications before approving them for these new drugs. It’s likely that Botox will be one of those drugs that patients have to fail.

My Thoughts on Cost

  • How many insurance policies will simply exclude these drugs? Writing this post prompted me to see what Botox costs with my current insurance coverage (which I’m quite happy with). I assumed I would have to pay 30% of the cost. Nope, Botox is not covered at all. Even if it my doctor says I need it and even if it’s the only drug in the world available for my condition, my insurance will not cover Botox. Will they really cover an even more expensive drug?
  • Although studies are looking at both episodic and chronic migraine, I wonder how difficult it will be to get insurance companies to cover the drugs for people with episodic migraine. Drug coverage restrictions often center around quantity, but what are the rules are for a drug where quantity is always the same? If a drug has FDA approval for episodic migraine, can insurance companies require that a person have a minimum number of migraine attacks per month before they’ll cover it? If so, will this ultimately mean only people with chronic migraine get the drug?
  • On the bright side, these new drugs are likely to bring down the cost of Botox.

 

Drug Safety is Still in Question

  • These drugs are in Phase 2 trials. Half of drugs fail in Phase 3 studies or do not receive FDA approval.
  • When Phase 3 trials test the drugs on thousands more patients, dangerous side effects could be discovered.
  • We don’t know what the long-term effects of inhibiting CGRP will be.
  • CGRP is distributed throughout the body and is involved in many process, including regulating blood flow and wound-healing.

My Thoughts on Safety

  • Thus far, studies have shown a low side effect risk for these drugs. This is encouraging, but studies have had limited numbers of participants. More people using the drugs—both in late-stage trials and, if approved, in widespread use—will be required before we can really know what the side effects will be.
  • The very novelty that makes these drugs exciting also makes them scary—CGRP hasn’t been inhibited before. What will the long-term effects of the drugs be? How will they impact other physiological processes? What will research find after the drugs have been in use five years? fifteen? thirty?
  • I probably wouldn’t be thinking much about the long-term safety if it weren’t for recent studies linking anticholinergic drugs to dementia and cognitive impairment. Anticholinergics have been used widely for at least 70 years, but the first of these studies (that I can find) was published just 11 years ago. How many people were negatively affected by these drugs before the link was found?

I’m still excited about the potential of the drugs, but my concerns weigh heavily. Maybe these worries will shake out by the time the drugs are available in a few years. Right now, I don’t see myself clamoring to try them as soon as they’re available… although if my migraine attacks are back to being severe by then, I’ll probably camping out to secure my place toward the front of the line.