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      Therapeutic novelties in migraine: new drugs, new hope?

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          Abstract

          Background

          In the past decade, migraine research has identified novel drug targets. In this review, we discuss recent data on emerging anti-migraine therapies.

          Main body

          The development of ditans, gepants and anti-calcitonin gene-related peptide monoclonal antibodies for the treatment of migraine is one of the greatest advances in the migraine field. Lasmiditan, rimegepant and ubrogepant will extend our therapeutic armamentarium for managing acute migraine attacks when triptans are not effective or contraindicated due to cardiovascular disorders. The monoclonal antibodies are migraine specific prophylactic drugs with high responder rates and favorable adverse event profiles. Furthermore, they offer convenient treatment regimens of 4- or 12-week intervals.

          Conclusion

          Collectively, novel migraine therapies represent a major progress in migraine treatment and will undoubtedly transform headache medicine.

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          Most cited references41

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          Pathophysiology of Migraine: A Disorder of Sensory Processing.

          Peter J Goadsby, Philip Holland, Margarida Martins-Oliveira … (2017)
          Plaguing humans for more than two millennia, manifest on every continent studied, and with more than one billion patients having an attack in any year, migraine stands as the sixth most common cause of disability on the planet. The pathophysiology of migraine has emerged from a historical consideration of the "humors" through mid-20th century distraction of the now defunct Vascular Theory to a clear place as a neurological disorder. It could be said there are three questions: why, how, and when? Why: migraine is largely accepted to be an inherited tendency for the brain to lose control of its inputs. How: the now classical trigeminal durovascular afferent pathway has been explored in laboratory and clinic; interrogated with immunohistochemistry to functional brain imaging to offer a roadmap of the attack. When: migraine attacks emerge due to a disorder of brain sensory processing that itself likely cycles, influenced by genetics and the environment. In the first, premonitory, phase that precedes headache, brain stem and diencephalic systems modulating afferent signals, light-photophobia or sound-phonophobia, begin to dysfunction and eventually to evolve to the pain phase and with time the resolution or postdromal phase. Understanding the biology of migraine through careful bench-based research has led to major classes of therapeutics being identified: triptans, serotonin 5-HT1B/1D receptor agonists; gepants, calcitonin gene-related peptide (CGRP) receptor antagonists; ditans, 5-HT1F receptor agonists, CGRP mechanisms monoclonal antibodies; and glurants, mGlu5 modulators; with the promise of more to come. Investment in understanding migraine has been very successful and leaves us at a new dawn, able to transform its impact on a global scale, as well as understand fundamental aspects of human biology.
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            Migraine--current understanding and treatment.

            Peter J Goadsby, Richard Lipton, Michel D. Ferrari (2002)
            Article 0 comments Cited 272 times – based on 0 reviews     Review now
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              ARISE: A Phase 3 randomized trial of erenumab for episodic migraine.

              David W Dodick, Messoud Ashina, Jan Brandes … (2018)
              Background Calcitonin gene-related peptide plays an important role in migraine pathophysiology. Erenumab, a human monoclonal antibody that inhibits the calcitonin gene-related peptide receptor, is being evaluated for migraine prevention. Methods In this randomized, double-blind, placebo-controlled, phase 3 study, 577 adults with episodic migraine were randomized to placebo or 70 mg erenumab; 570 patients were included in efficacy analyses. Primary endpoint was change in monthly migraine days. Secondary endpoints were ≥50% reduction in monthly migraine days, change in acute migraine-specific medication treatment days, and ≥5-point reduction in Physical Impairment and Impact on Everyday Activities domain scores measured by the Migraine Physical Function Impact Diary. All endpoints assessed change from baseline at month 3. Results Patients receiving erenumab experienced -2.9 days change in monthly migraine days, compared with -1.8 days for placebo, least-squares mean (95% CI) treatment difference of -1.0 (-1.6, -0.5) ( p < 0.001). A ≥ 50% reduction in monthly migraine days was achieved by 39.7% (erenumab) and 29.5% (placebo) of patients (OR:1.59 (95% CI: 1.12, 2.27) ( p = 0.010). Migraine-specific medication treatment days were reduced by -1.2 (erenumab) and -0.6 (placebo) days, a treatment difference of -0.6 (-1.0, -0.2) ( p = 0.002). The ≥5-point reduction rates in Migraine Physical Function Impact Diary - Physical Impairment were 33.0% and 27.1% (OR:1.33 (0.92, 1.90) ( p = 0.13) and in Migraine Physical Function Impact Diary - Everyday Activities were 40.4% and 35.8% (OR:1.22 (0.87, 1.71) ( p = 0.26). Safety and adverse event profiles of erenumab were similar to placebo. Most frequent adverse events were upper respiratory tract infection, injection site pain, and nasopharyngitis. Conclusions As a preventive treatment of episodic migraine, erenumab at a dosage of 70 mg monthly significantly reduced migraine frequency and acute migraine-specific medication use. (Funded by Amgen). Trial registration ClinicalTrials.gov, NCT02483585.
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                Author and article information

                Contributors
                Thien Phu Do: thiendo@gmail.com
                Song Guo: song60887727@gmail.com
                Messoud Ashina: ashina@dadlnet.dk
                Journal
                Journal ID (nlm-ta): J Headache Pain
                Journal ID (iso-abbrev): J Headache Pain
                Title: The Journal of Headache and Pain
                Publisher: Springer Milan (Milan )
                ISSN (Print): 1129-2369
                ISSN (Electronic): 1129-2377
                Publication date (Electronic): 17 April 2019
                Publication date PMC-release: 17 April 2019
                Publication date Collection: 2019
                Volume: 20
                Issue: 1
                Electronic Location Identifier: 37
                Affiliations
                ISNI 0000 0001 0674 042X, GRID grid.5254.6, Danish Headache Center and Department of Neurology, Rigshospitalet Glostrup, Faculty of Health Sciences, , University of Copenhagen, ; Copenhagen, Denmark
                Article
                Publisher ID: 974
                DOI: 10.1186/s10194-019-0974-3
                PMC ID: 6734360
                PubMed ID: 30995909
                SO-VID: 5c4bc95f-fd1f-4451-9108-b851db87cca4
                Copyright © © The Author(s). 2019
                License:

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                Date received : 26 December 2018
                Date accepted : 18 February 2019
                Categories
                Subject: Review Article
                Custom metadata
                issue-copyright-statement © The Author(s) 2019

                ScienceOpen disciplines: Anesthesiology & Pain management
                Keywords: migraine,randomized clinical trial,efficacy,tolerability,adverse event,ditan,gepant,antibody
                Data availability:
                ScienceOpen disciplines: Anesthesiology & Pain management
                Keywords: migraine, randomized clinical trial, efficacy, tolerability, adverse event, ditan, gepant, antibody

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