Dear Colleagues,

Although largely underestimated and underappreciated, migraine affects more than one billion people across the world [1] and stands as the first cause of disability among all medical conditions in people younger than 50 [2]. Multidisciplinary management limits the burden of migraine significantly; however, that includes medicinal and nonmedicinal treatments as well as symptomatic for the relief of attacks and prophylactic ones for the restriction of the disease by attenuating the frequency and severity of attacks. Depending on the frequency of the attacks, migraine is classified into episodic and chronic subforms. Chronic migraine is characterized by 15 or more headache days per month of which at least 8 days show typical migraine features, and episodic migraine is characterized by less than 15 headache days per month. The development from episodic to chronic migraine, referred to as migraine chronification, is estimated to occur in 2.5% of the patients with episodic migraine annually, but only a few chronic migraine cases revert back to episodic subform [3]. While episodic migraine affects the quality of life significantly, the impact of chronic migraine in daily life is enormous [4]. Thus, one of the migraine treatment milestones refers to the prevention of migraine chronification, because in chronic migraine, all migraine characteristics are considerably enlarged, and the condition evolves into a difficult-to-treat condition with several comorbidities, including the overuse of symptomatic medications. Although triptans, disease-specific, and mechanism-based drugs for symptomatic treatment for migraine have been available since the early 1990s, only repurposed drugs were until recently available for prophylactic pharmaceutical treatment, embracing mainly anti-hypertensive, antiepileptic and antidepressant agents. However, these pharmaceutical options often cause low adherence due to safety reasons [5]. The scene changed dramatically with the introduction of novel pharmaceutical treatments targeting the calcitonin-gene-related peptide (CGRP), either as small molecules that penetrate the blood–brain barrier, i.e., so-called gepants, or as large ones, the monoclonal antibodies to CGRP ligand and receptor that act peripherally [6]. The therapeutic developments are complemented by new neurostimulation techniques and disease-specific symptomatic drugs, i.e., ditans.

The plethora of the novel antimigraine agents consequently raises questions around prioritizing and practice dilemmas. Eventually, decision making, e.g., choosing the right treatment for the right person, or when and how to escalate the treatment, presupposes a correct and detailed knowledge of the mechanism of action and the efficacy and safety results of clinical trials of each antimigraine agent. Several charities associated to the field have published related recommendations already [7,8], but treating physicians should have a basic knowledge in order to form a personal opinion about their particular patients, who may display a specific clinical picture in a specific context of coherence that imposes specific treatment rules. This is precisely the aim of the present issue, to cover all aspects related to the management of migraine with monoclonal antibodies, in order to help treating physicians to take the correct therapeutic decisions after consulting the patient about their preferences.

References

1. GBD 2016 Neurology Collaborators. Global, regional, and national burden of migraine and tension-type headache, 1990–2016: A systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 2019, 18, 459–480. doi:10.1016/S1474-4422(18)30499-X.
2. Steiner, T.J.; Stovner, L.J.; Vos, T.; Jensen, R.; Katsarava, Z. Migraine is first cause of disability in under 50s: Will health politicians now take notice? Headache Pain 2018, 19, 17. doi:10.1186/s10194-018-0846-2.
3. Torres-Ferrús, M.; Ursitti, F.; Alpuente, A.; Brunello, F.; Chiappino, D.; de Vries, T.; Di Marco, S.; Ferlisi, S.; Guerritore, L.; Gonzalez-Garcia, N.; Gonzalez-Martinez, A.; Khutorov, D.; Kritsilis, M.; Kyrou, A.; Makeeva, T.; Minguez-Olaondo, A.; Pilati, L.; Serrien, A.; Tsurkalenko, O.; Van den Abbeele, D.; van Hoogstraten, W.S.; Lampl, C.; School of Advanced Studies of European Headache Federation (EHF-SAS). From transformation to chronification of migraine: Pathophysiological and clinical aspects. Headache Pain 2020, 21, 42. doi:10.1186/s10194-020-01111-8.
4. Burch, R.C.; Buse, D.C.; Lipton, R.B. Migraine: Epidemiology, Burden, and Comorbidity. Neurol Clin. 2019, 37, 631–649. doi:10.1016/j.ncl.2019.06.001.
5. Hepp, Z.; Dodick, D.W.; Varon, S.F.; Gillard, P.; Hansen, R.N.; Devine, E.B. Adherence to oral migraine-preventive medications among patients with chronic migraine. Cephalalgia 2015, 35, 478–88. doi:10.1177/0333102414547138.
6. Charles, A.; Pozo-Rosich, P. Targeting calcitonin gene-related peptide: A new era in migraine therapy. Lancet 2019, 394, 1765–1774. doi:10.1016/S0140-6736(19)32504-8.
7. Sacco, S.; Bendtsen, L.; Ashina, M.; Reuter, U.; Terwindt, G.; Mitsikostas, D.D.; Martelletti, P. European headache federation guideline on the use of monoclonal antibodies acting on the calcitonin gene related peptide or its receptor for migraine prevention. Headache Pain 2019, 20, 6. doi:10.1186/s10194-018-0955-y.
8. American Headache Society. The American Headache Society Position Statement on Integrating New Migraine Treatments into Clinical Practice. Headache 2019, 59, 1–18. doi:10.1111/head.13456.

Prof. Dimos D. Mitsikostas
Guest Editor

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