After estimating that migraines lead to tens of billions of dollars in lost productivity in Australia, the authors of a health and productivity analysis concluded that funding towards reducing the prevalence and effects of migraine is likely to be “a sound return on investment.”1 Neurologists now have further options available for patients in whom migraine continues to impact their lives with effective PBS-funded prophylactic therapy now available in the form of calcitonin gene-related peptide (CGRP) inhibitors.2,3
The burden of migraine
Neurologist Nicole Limberg, Director of Migraine Specialist in Brisbane, described how the impact of migraines on individuals and their families is broader than the actual pain of the migraine itself.
“Disability is two-fold: a significant amount of pain and other migraine phenomena, including the nausea, the light sensitivity, the irresistible urge to just crawl up in a ball in a dark room and go to sleep,” she said. “And for those unlucky enough to suffer from the aura, you also have neurological disability on top of the pain and hypersensitivity phenomena the patient is experiencing,” she explained.
Regular migraine episodes can lead to further disability in functioning related to the unpredictable nature of the events. “These patients cannot predict when this is going to happen. They spend countless amounts of hours trying to find triggers so that they feel some kind of control or strategy that could minimise the likelihood of these attacks…So there’s another aspect of disability where they will not commit to things or say yes to things for fear of letting people down…fear of being caught somewhere when this event occurs,” said Dr Limberg.
Patient assessment beyond counting monthly headache days
Chronic migraine is defined as “headaches on at least 15 days per month for at least 3 months with the features of migraine on at least 8 days per month.”3 Although chronic migraine is associated with greater burden to the patient and to society and requires preventive therapy,4 even patients with difficult-to-treat episodic migraine or migraine that occurs more frequently than three times per month may require prophylaxis.5
“As a neurologist you’re considering many things, including how significantly the migraine’s affecting the patient’s life. We do use validated scales, as well as numbers of reported headache days and migraine days. The difference between these is: is it a background milder headache they’re experiencing? And a lot of them would have this on a daily base. The migraine would be counted based on how many times that month does it meet more significant disability: having to leave work early, or having to take a triptan, or having to go to the emergency department, or having to lie down,” explained Dr Limberg.
Objective measures include migraine inventory scales, such as the Headache Impact Test (HIT6TM)6 and the Migraine Disability Assessment Score (MIDAS),7 which help measure the impact of the headache event on function.
Beyond migraine headache days (MHDs), other impacts of migraine need to be considered when deciding on the best management approach, explained Dr Limberg. “Another aspect we look at is how effective is their acute treatment…If they’re having severe events and they’ve taken medication and they’re back on board in twenty minutes, that’s a different conversation to when they’re having severe events and they’ve taken medication and it’s not working. We’re generally looking at whether the migraine event is terminated within two hours as to whether the acute therapy is working,” she said.
“In terms of where we will draw a line in the sand for instituting oral preventive therapy, that would generally be about four attacks per month…but you’ll make that individual call based on the severity and patient preference,” said Dr Limberg.
“I allow quite a lot of time for the patients because the story is so important,” said Dr Limberg. “The story really does give the picture of the impact the migraine has in their lives. We obtain that information from getting to know the patient. We do look for collaborative evidence [from GP notes etc.]. Patients will also say things like, “The pharmacist said, ‘You’re here again…maybe it’s time you went to see a neurologist’,” she explained.
Assessment and shared decision making
The American Headache Society Position Statement on Integrating New Migraine Treatments into Clinical Practice8 notes that the goals of preventive therapy are not only to reduce episode frequency, severity and disability, but also to enable patients to manage their own disease and enhance of sense of personal control. To that end, one of the indications of preventive therapy – other than frequency of attacks – is patient preference.8
Patient preference for preventive therapy is not always related to episode frequency or duration, notes Dr Limberg. “When you have a conversation with the patient on their preference, some will say, ‘Yes all of this has happened but I don’t want to take a daily [preventive] medication; I just want to talk to you about triptan therapy.’ Others will have one significant event per month and will say ‘I want to talk about prevention because it was unacceptable that it happened to me and I’m not happy with that,’” she explained.
The need for more effective preventive therapies
Before the introduction of CGRP inhibitors, all oral prophylactic drugs for migraine were developed for other conditions, including hypertension, depression and epilepsy. A recent drug utilisation study9 in 12,894 people with migraine found that of the 10.7% of patients prescribed prophylactic treatment, just over a quarter (26.2%) adhered to their initial treatment. Of those who reported interruptions in treatment, almost half (46.4%) discontinued treatment completely within 103 days. A third (31%) restarted treatment 46 days after interruption, and 22.6% switched to another treatment within 98 days. Commenting on the poor treatment adherence, the investigators concluded, “These findings reflect an unmet need for improved prophylactic therapies in order to provide a better disease management.”9
CGRP inhibitors were developed for migraine prevention
The CGRP inhibitors are the first category of drugs developed to specifically target migraine prevention.10 The monoclonal antibody galcanezumab (Emgality) binds to CGRP and prevents its activity without blocking the CGRP receptor;10 it was listed on the PBS in June 2021 as Authority Required (Streamlined) for the preventive treatment of chronic migraine.2 The patient must have experienced an inadequate response, intolerance or a contraindication to at least three prophylactic migraine medicines, and treatment cannot be used in combination with botulinum toxin.2
Emgality monthly subcutaneous injection significantly reduces the number of migraine headache days per month compared to placebo in both episodic and chronic migraine.11–14 In chronic migraine, galcanezumab showed greater reductions in the number of monthly migraine headache days for which acute therapy was taken compared with placebo. Patients treated with galcanezumab also reported greater improvement in functioning and a significant reduction in disability compared to placebo.11,14
An open-label study found that efficacy was sustained for up to one year in both patients with episodic migraine and those with chronic migraine.11
The most common adverse reactions (120mg dose) were injection site pain (10.1%), injection site reactions (9.9%), vertigo (0.7%), constipation (1.0%), pruritis (0.7%) and urticaria (0.3%). Most reactions were mild to moderate in intensity.11
“It’s another option to have in the armamentarium for the refractory patient. Overall we’ve had a very good experience with the CGRP inhibitors. They’re well tolerated and effective for a sizeable number of patients, with 50-60% of patients achieving a benefit,” said Dr Limberg.
This article was commissioned by Eli Lilly Australia Pty Ltd. The content is independent and based on studies and the author’s opinion. The views expressed do not necessarily reflect the views of Eli Lilly. Before prescribing please review the Emgality (link) full product information via the TGA website. Treatment decisions based on these data are the responsibility of the prescribing physician.
- Tu S et al. The health and productivity burden of migraines in Australia. Headache 2020; 60(10):2291–2303.
- Emgality PBS Authority (Streamlined) Listing
- Ajovy PBS Authority (Streamlined) Listing
- Lipton RB and Silberstein SD. Episodic and chronic migraine headache: breaking down barriers to optimal treatment and prevention. Headache 2015; 55 (Suppl2):103 – 122.
- Jenkins B. Migraine Management. Aust Presc 2020;43:148 – 151.
- Yang M et al. Validation of the Headache Impact Test (HIT-6TM) across episodic and chronic migraine. Cephalalgia 2011;31(3):357–367.
- Stewart WF, et al. Validity of the Migraine Disability Assessment (MIDAS) score in comparison to a diary-based measure in a population sample of migraine sufferers. Pain 2000, 88(1): 41-52
- American Headache Society. The American Headache Society Position Statement on Integrating New Migraine Treatment into Clinical Practice. Headache 2019; 59:1–18.
- Orlando V et al. Treatment patterns and medication adherence among newly diagnosed patients with migraine: a drug utilization study. BMJ Open 2020;10:e038972.
- Mohanty D and Lippmann S. CGRP inhibitors for migraine. ICNS 2020; 17:4-6
- Emgality Product Information
- Stauffer VL et al. Evaluation of Galcanezumab for the Prevention of Episodic Migraine: The EVOLVE-1 Randomized Clinical Trial. JAMA Neurol 2018;75(9):1080–8.
- Skljarevski V et al. Efficacy and safety of galcanezumab for the prevention of episodic migraine: Results of the EVOLVE-2 Phase 3 randomized controlled clinical trial. Cephalalgia 2018;38(8):1442–54.
- Detke HC et al. Galcanezumab in chronic migraine: The randomized, double-blind, placebo-controlled REGAIN study. Neurology 2018;91(24):e2211–21