“Migraine is more than just the headache. It’s a condition that significantly impacts patients’ quality of life. It can disrupt everyday activities, potentially lead to fear about the next attack and avoidance of many things in the person’s  lifestyle”,” said Dr Bronwyn Jenkins, a consultant neurologist at the Epping Clinic in Sydney.  In November the limbic sat down with Dr Jenkins to talk about migraine and to uncover practical advice on how to prevent and manage migraine, in light of the preventive medications available in Australia.

According to Dr Jenkins, “even moderate migraine attacks can include impaired concentration and fatigue, disrupting everyday activities. It’s important to note that the burden of migraine is not limited to ‘days with headache’, as premonitory symptoms can occur from 2 to 72 hours before the attack and postdromal symptoms can continue after the headache itself dissipates.”

Despite the significant impact on patients’ lives, migraine remains under or misdiagnosed and undertreated in general practice.¹ Patients also frequently underreport the total number of headache days, reporting only what Dr Jenkins referred to as “the showstoppers”.¹ Notably, 40% of people with migraine meet criteria for preventive medications, but less than 25% of these patients actually use them. ²

The International Classification of Headache Disorders recognises three main types of migraine. These are:³

Acute treatment

Australian guidelines recommend treating acute migraines at the onset of symptoms with nonopioid analgesics, adding an antiemetic to improve response to analgesia or treat associated nausea. For patients with poor response or severe symptoms, treatment with a triptan is recommended.^4,5

Prevention

In Australia, prophylaxis is indicated for patients who experience two or more severe migraines per month that significantly impair quality of life (QoL) and do not respond well to acute treatments.⁵ Patients who are refractory to multiple preventive medications may be eligible for treatment with botulinum toxin injections in the head and neck.⁴

CGRPs and migraine prevention

Dr Jenkins noted that “until recently, preventive migraine therapy has relied on oral medications borrowed from other indications—largely antihypertensive, antiepileptic, and antidepressant medications. However, discontinuation rates with these agents are high due to limited effectiveness and poor tolerability.^” Enter calcitonin gene-related peptide (CGRP) antagonists—preventive agents that specifically target one of the steps in the pathophysiology of migraine.⁶ CGRP is a vasodilating neuropeptide involved in peripheral and central sensitisation and pain perception.^4,10 CGRP antagonists are monoclonal antibodies directed at the CGRP ligand (galcanezumab, fremanezumab, eptinezumab) or the CGRP receptor (erenumab).^6,7 They inhibit the action or binding of circulating CGRP molecules, which are elevated during migraine attacks.^2,6,7

CGRP monoclonal antibody therapies exhibit effectiveness similar to established daily oral preventive medications, with longer half-lives that allow for reduced frequency of dosing.^6,7 Data from placebo-controlled clinical trials with galcanezumab show that monthly treatment significantly reduced the number of monthly migraine headache days (MHDs) by 4.3 to 4.8 days over 6 months in patients with episodic migraine and 3 months in patients with chronic migraine vs placebo.^2,8,9 In some patients MHDs were reduced at month one with effects seen as early as one week.⁹ Patients who previously failed one or more prophylactic treatments saw significant benefit, as did patients with acute headache medication overuse.^9,10

Are CGRPs right for my patient?

There are currently no Australian guidelines for determining which patients should receive CGRPs. Access to CGRPs in Australia is limited, as they are currently not listed on the Pharmaceutical Benefits Scheme. Dr Jenkins surmised that “recently, the American Headache Society recommended that CGRPs should only be considered in patients with a documented intolerance or inadequate response to 6-week trials of two or more classes of preventive migraine medications.^”

Optimising migraine prevention

Dr Jenkins outlined the following practical advice for optimising prevention therapies for migraine – highlighting that “this is an exciting field with patients that are highly rewarding to treat. Being such a debilitating condition, improvements can equate to marked improvements in function and quality of life”:

References:

1. Kingston WS, Halker R. Determinants of suboptimal migraine diagnosis in the primary care setting. J Clin Outcomes Manag. 2017;24(7).
2. Martin V, Samaan KH, Aurora S, et al. Efficacy and Safety of Galcanezumab for the Preventive Treatment of Migraine: A Narrative Review. Adv Ther. 2020;37(5):2034-2049.
3. Headache Classification Committee of the International Headache Society (IHS) The International Classification of Headache Disorders, 3rd edition. Cephalalgia. 2018;38(1):1-211.
4. Migraine [published November 2017; amended January 2019]. In: eTG complete[digital]. Melbourne: Therapeutic Guidelines Limited; August 2020. https://www.tg.org.au. Accessed November 2020.
5. Australian Medicine Handbook (online). Migraine. Adelaide: Australian Medicines Handbook Pty Ltd; July 2020. https://amhonline.amh.net.au. Accessed November 2020.
6. Bucklan J, Ahmed Z. CGRP antagonists for decreasing migraine frequency: New options, long overdue. Cleve Clin J Med. 2020;87(4):211-218.
7. Scuteri D, Adornetto A, Rombolà L, et al. New Trends in Migraine Pharmacology: Targeting Calcitonin Gene-Related Peptide (CGRP) With Monoclonal Antibodies. Front Pharmacol. 2019;10:363.
8. Gklinos P, Mitsikostas DD. Galcanezumab in migraine prevention: a systematic review and meta-analysis of randomized controlled trials. Ther Adv Neurol Disord. 2020;13:1756286420918088.
9. Eli Lilly. Emgality® Australian Product Information. May 2019.
10. Mulleners WM, Kim BK, Láinez MJA, et al. Safety and efficacy of galcanezumab in patients for whom previous migraine preventive medication from two to four categories had failed (CONQUER): a multicentre, randomised, double-blind, placebo-controlled, phase 3b trial. Lancet Neurol. 2020;19(10):814-825.
11. American Headache Society. The American Headache Society Position Statement On Integrating New Migraine Treatments Into Clinical Practice [published correction appears in Headache. 2019 Apr;59(4):650-651]. Headache. 2019;59(1):1-18.
12. Blumenfeld AM. Clinician-Patient Dialogue About Preventive Chronic Migraine Treatment. J Prim Care Community Health. 2020;11:2150132720959935.