Cheap Migraine Drugs More Effective Than New Expensive Ones

By Pat Anson

Migraine treatment drugs known as triptans are more effective in relieving acute migraine pain than new expensive medications and should be used more widely, according to new study published in The BMJ.

A team of researchers at Oxford University analyzed the results from 137 clinical studies to see which migraine drugs were more effective in helping patients become pain-free after two hours and whether that relief was sustained 24 hours later. Nearly 90,000 people participated in the studies, over 85% of them women.

Four triptans - eletriptan, rizatriptan, sumatriptan, and zolmitriptan – were rated the best overall, ahead of rimegepant (Nurtec), ubrogepant (Ubrelvy) and lasmiditan (Reyvow) in efficacy and tolerability.

“Overall, the results of our network meta-analysis suggest that the best performing triptans should be considered the treatment of choice for migraine episodes owing to their capacity for inducing rapid and sustained pain freedom, which is of key importance for people with migraine,” wrote lead author Andrea Cipriani, MD, a professor of psychiatry and director of the Precision Psychiatry Lab at Oxford.

Triptans work by narrowing blood vessels in the brain and preventing the release of chemicals that cause migraine pain; while rimegepant and ubrogepant inhibit calcitonin gene-related peptides (CGRPs), a protein that triggers pain. Lasmiditan reduces pain by binding to serotonin receptors in the brain.

The drugs’ mechanisms of action are different and so is their cost. A packet of 6 tablets of eletriptan costs about $106, while a similar-sized packet of rimegepant (Nurtec) costs $1,061; ubrogepant (Ubrelvy) costs $1,097; and lasmiditan (Reyvow) is priced at $790. The cost of those three drugs is much higher because they are only available as brand name medications, while triptans are widely available in cheaper generic formulations.

Despite their cost and extensive marketing promoting their use, lasmiditan, rimegepant, and ubrogepant were rated no more effective in treating migraine pain than over-the-counter drugs such as acetaminophen (paracetamol) and non-steroidal anti-inflammatory drugs (NSAIDs). Researchers say those OTC pain relievers should be considered second line options, if triptans are ineffective.  

“While the recent introduction of lasmiditan, rimegepant, and ubrogepant has expanded options for the acute treatment of migraine, the high cost of these newer drugs, along with the substantial adverse effects of lasmiditan (dizziness), suggest their use as third line options, after the less expensive, similarly efficacious, second line options,” researchers said.

“Limited access to triptans and their substantial under-utilization represents missed opportunities to offer more effective treatments and deliver better quality of care to people who experience migraine.”

Some people can’t take triptans due to cardiovascular problems or unwanted side effects, but researchers say the best performing triptans should be included in the World Health Organization’s List of Essential Medicines to help expand their use.

Another recent study also rated triptans as superior to other migraine medications, although that research didn’t include the newer CGRP inhibitors.

Migraine affects about 39 million people in the United States and 1.1 billion worldwide. In addition to headache pain, migraine can cause nausea, blurriness, and sensitivity to light or sound. Women are three times more likely to suffer from migraines than men.  

Cheap Drugs May Prevent Migraine Just as Effectively as Expensive Ones

By Pat Anson, PNN Editor

Two drugs commonly used to treat depression and high cholesterol are just as effective at preventing migraine as CGRP inhibitors, according to a large new study.

They are also a heck of a lot cheaper.  

Researchers at the Norwegian Center for Headache Research analyzed the prescription drug history of over 100,000 migraine patients in Norway from 2010 to 2020. Their goal was to see if patients reduced their use of medications used to treat acute migraine pain – such as triptan – once they started taking drugs used to prevent migraine.

“When the withdrawal of acute migraine medicines changed little after starting preventive medicines, or people stopped quickly on the preventive medicines, the preventive medicine was interpreted as having little effect,” explained lead investigator Marte-Helen Bjørk, MD, a Professor in the Department of Clinical Medicine, University of Bergen.

“If the preventive medicine was used on long, uninterrupted periods, and we saw a decrease in the consumption of acute medicines, we interpreted the preventive medicine as having good effect.”

Beta blockers are often the first drugs used to prevent migraine attacks, but Bjørk and her colleagues found that three other medications were associated with lesser use of triptans: amitriptyline, simvastatin and CGRP inhibitors.

Amitriptyline is a tricyclic antidepressant that is mostly taken for depression, while simvastatin is a statin used to treat high cholesterol. Both drugs are also used off-label for migraine prevention.

CGRP inhibitors are a relatively new class of medication that block calcitonin gene-related peptides, a protein that binds to nerve receptors in the brain and triggers migraine pain. Since 2018, the FDA has approved over half a dozen CGRP medications, which are considered the biggest innovation in migraine treatment in decades.

However, CGRP drugs are not cheap. Eight doses of Nurtec, a tablet taken daily to prevent and treat migraine, can cost over $1,000, while the listed price for Emgality is $679 for a self-injectable syringe used once a month for migraine prevention. Prices will vary for patients, depending on insurance and whether they qualify for a patient assistance program.

By comparison, amitriptyline and simvastatin are screaming bargains. A bottle of 30 simvastatin tablets will cost about $14, while amitriptyline costs about $13 for a supply of 28 tablets.

When it comes to reducing triptan use, amitriptyline, simvastatin and the CGRP inhibitors performed about the same. During the first 90 days of treatment, nearly 57% of patients taking simvastatin reduced their triptan use, compared to 53% of patients taking amitriptyline and 55% of those taking CGRP medicines.

The study findings, recently published in the European Journal of Neurology, show that patients taking beta blockers, topiramate or clonidine were more likely to keep taking triptans.

“Our analysis shows that some established and cheaper medicines can have a similar treatment effect as the more expensive ones. This may be of great significance both for the patient group and Norwegian health care” says Bjørk, who has already started work on a clinical trial to see if other cholesterol-lowering drugs can prevent migraine.

Migraine affects about 1 billion people worldwide and 39 million in the United States, according to the American Migraine Foundation. In addition to headache pain, migraine can cause nausea, blurriness or visual disturbances, and sensitivity to light and sound. Women are three times more likely to suffer from migraines than men.

New Test Predicts Effectiveness of CGRP Drugs for Migraine

By Pat Anson, PNN Editor

CGRP inhibitors have been one of the biggest innovations in migraine treatment in decades. CGRP stands for calcitonin gene-related peptides, a protein that binds to nerve receptors in the brain and triggers migraine pain. Since 2018, the FDA has approved over half a dozen CGRP inhibitors for migraine prevention and treatment.

The problem with anti-CGRP therapies – besides their high cost – is that they only work for about half the people who take them.

A new test may take some of the guesswork out of CGRP therapy, by predicting with about 80% accuracy which patients will respond to CGRP inhibitors before treatment begins.  In a small study published in the journal Cephalalgia, Harvard Medical School researchers found that most migraine patients with non-ictal cephalic allodynia -- pain sensitivity experienced in-between migraine attacks – did not respond to CGRP treatment. Conversely, most patients without non-ictal cephalic allodynia did respond to CGRP therapy.  

Determining which patients have or don’t have cephalic allodynia is relatively easy, through a novel Quantitative Sensory Testing (QST) algorithm that measures how sensitive patients are to heat, cold and being poked in the skin with a sharp object. The test identified CGRP responders with nearly 80% accuracy and non-responders with nearly 85% accuracy.

“Detection of non-ictal cutaneous allodynia with a simplified paradigm of QST may provide a quick, affordable, non-invasive, and patient-friendly way to prospectively distinguish between responders and non-responders to the prophylactic treatment of migraine with drugs that reduce CGRP signaling,” wrote lead author Rami Burstein, MD, Professor of Anesthesia, Harvard Medical School.

Burstein helped develop the QST test in collaboration with CGRP Diagnostics. The test can be done in about five minutes in a doctor’s office.

“This is all about improving outcomes for people suffering from migraines and so we strongly recommend that all potential anti-CGRP recipients have the test done prior to prescription,” said Mark Hasleton, PhD, CEO of CGRP Diagnostics. 

“This will help provide migraine sufferers with either the best chance for treatment success for likely responders, or to enable rapid transition for likely non-responders to other treatment strategies, thus avoiding the misery of treatment failure. CGRP Diagnostics is currently in discussions with multiple key pharma and payor players in this area, with the expectation that such a test will become a prerequisite prior to anti-CGRP prescription.”

A surprise finding from the study is that cutaneous allodynia may be related to genetic factors that cause pain sensitivity, rather than the frequency or severity of migraines.

“This study unveils the mechanism of physiological response to anti-CGRP therapy and could fundamentally change the anti-CGRP therapy field,” said Iris Grossman, PhD, Founding Scientific Advisor at CGRP Diagnostics. “We now have an objective tool to tailor early and effective therapy to migraine sufferers. This novel test holds the potential for earlier access to anti-CGRP therapy, reduced need for prior treatment failures with generics, and enhanced formulary access. It also enables non-responders to rapidly transition to other treatment strategies, preventing a great deal of suffering and frustration for all.”

A 2020 survey of migraine patients by Health Union found that 52% of those who tried a CGRP therapy switched brands because the treatment didn’t work or because they didn’t like the side effects, such as constipation and weight gain.

CGRP medications are not cheap. Eight doses of Nurtec, the migraine treatment endorsed by Khloe Kardashian, can cost over $1,000 without insurance.

Migraine affects more than 37 million people in the United States, according to the American Migraine Foundation. In addition to headache pain, migraine can cause nausea, blurriness or visual disturbances, and sensitivity to light and sound. Women are three times more likely to suffer from migraines than men.

Advocacy Group Calls on Insurers to Modify Step Therapy for Migraine Treatment

By Pat Anson. PNN Editor

The National Headache Foundation (NHF) is calling on health insurers to stop using rigid “step therapy” policies and make it easier for migraine patients to get access to new treatments.

Step therapy is a common practice in the insurance industry to control costs. It requires patients to try cheaper and often older medications first, before “stepping up” to drugs that cost more.   

“For too long, migraine patients have been treated differently than others with medical issues as it relates to access to prescription medications. Specifically, clinicians are often forced to use outdated prescription drugs in a stepwise approach to all patients, without considering the needs of the individual patient,” said Thomas Dabertin, Executive Director/CEO of NHF, a non-profit that seeks to raise awareness about migraine and headache disorders.  

“Unfortunately, the current care models adopted by payers have not kept pace with the many advances in treatment. As a result, clinicians are using older medications, some of which are not even designed for the specific treatment of migraine, even though new migraine-specific therapies now exist.”

Migraine treatment has been revolutionized in recent years by the introduction of neuromodulation devices and drugs that inhibit calcitonin gene-related peptides (CGRP), proteins that cause migraine pain. CGRP inhibitors cost several thousand dollars a year, while neuromodulation devices usually cost several hundred dollars.

Older drugs used to treat or prevent migraine, such as triptans, antidepressants and over-the-counter pain relievers, are much cheaper and often come in generic formulations. Many Insurers require patients to try at least two of the older medications first -- and for months at a time -- before authorizing newer therapies.

“NHF believes it is inappropriate to require all patients to follow this ‘try two and fail’ model before they may be offered treatment with any FDA-approved migraine preventive, including neuromodulation devices, with established lower adverse event profiles,” the NHF said in a position statement.

“For patients who are highly impacted or disabled by migraine, clinicians should not be directed to deliver outdated models of care that apply a predetermined algorithm in a stepwise approach to all patients, without considering the needs of the individual patient, and that encourage the use of older preventive drugs when targeted and migraine-specific therapies now exist.”

The NHF wants insurers to adopt modified forms of step therapy for migraine sufferers, based on the severity of their disease and the frequency of their attacks.

For patients who have seven or fewer migraine days per month, the NHF recommends that patients be required to try only one generic drug for migraine prevention. For patients who experience 8 or more migraine days per month, the foundation recommends that providers have “unfettered access” to FDA-approved prevention drugs.

For the treatment of acute migraine pain, the NHF recommends that two generic drugs be tried first, but if the drugs fail to work within two hours or have unwelcome side effects, providers be allowed to select “another suitable therapy” based on a patient’s needs.  

“The NHF advocates that payers adopt care models that are patient-centric, where the clinician, in collaboration with the patient, is the primary decision-maker and selects a treatment that addresses the patient’s treatment goals and needs,” Dabertin said.

Although the NHF accepts donations from the pharmaceutical industry, Dabertin told PNN the foundation’s new position statement was based solely on input from patients and providers.