351
Views
0
CrossRef citations to date
0
Altmetric
Review

The impact of CGRPergic monoclonal antibodies on prophylactic antimigraine therapy and potential adverse events

ORCID Icon, ORCID Icon & ORCID Icon
Pages 1223-1235 | Received 29 Apr 2021, Accepted 15 Sep 2021, Published online: 04 Oct 2021

References

  • Goadsby PJ, Lipton RB, Ferrari MD. Migraine — Current understanding and treatment. N Engl J Med. 2002;346(4):257–270.
  • Headache Classification Committee of the International Headache Society (IHS) The international classification of headache disorders. 3rd edition. Cephalalgia. 2018;38:1–211.
  • Villalón CM, MaassenVanDenBrink A. The role of 5-hydroxytryptamine in the pathophysiology of migraine and its relevance to the design of novel treatments. Mini Rev Med Chem. 2017;17(11):928–938.
  • Villalón CM, Olesen J. The role of CGRP in the pathophysiology of migraine and efficacy of CGRP receptor antagonists as acute antimigraine drugs. Pharmacol Ther. 2009;124(3):309–323.
  • Andlin-Sobocki P, Jonsson B, Wittchen H-U, et al. Cost of disorders of the brain in Europe. Eur J Neurol. 2005;12(S1):1–27.
  • Stovner LJ, Nichols E, Steiner TJ, GBD 2016. 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. 2018;17(11):954–976.
  • Villalón CM, Centurión D, Valdivia LF, et al. Migraine: Pathophysiology, pharmacology, treatment and future trends. Curr Vasc Pharmacol. 2003;1(1):71–84.
  • Rubio-Beltrán E, Labastida-Ramírez A, Villalón CM, et al. Is selective 5 HT1F receptor agonism an entity apart from that of the triptans in antimigraine therapy? Pharmacol Ther. 2018;186:88–97.
  • González-Hernández A, Marichal-Cancino BA, MaassenVanDenBrink A, et al. Side effects associated with current and prospective antimigraine pharmacotherapies. Exp Opin Drug Metab Toxicol. 2018;14:25–41.
  • González-Hernández A, Marichal-Cancino BA, García-Boll E, et al. The locus of action of CGRPergic monoclonal antibodies against migraine: peripheral over central mechanisms. CNS Neurol Disord. 2020;19:344–359.
  • Rivera-Mancilla E, Villalón CM, MaassenVanDenBrink A. CGRP inhibitors for migraine prophylaxis: a safety review. Exp Opin Drug Saf. 2020;19:1237–1250.
  • González-Hernández A, Condés-Lara M, García-Boll E, et al. An outlook on the trigeminovascular mechanisms of action and side effects concerns of some potential neuropeptidergic antimigraine therapies. Exp Opin Drug Metab Toxicol. 2021;17:179–199.
  • Jeong HJ, Mitchell VA, Vaughan CW. Role of 5-HT1 receptor subtypes in the modulation of pain and synaptic transmission in rat spinal superficial dorsal horn. Br J Pharmacol. 2012;165:1956–1965.
  • Marichal-Cancino BA, González-Hernández A, ManriqueMaldonado G, et al. Intrathecal dihydroergotamine inhibits capsaicin-induced vasodilatation in the canine external carotid circulation via GR127935- and rauwolscine-sensitive receptors. Eur J Pharmacol. 2012;692:69–77.
  • Russell FA, King R, Smillie SJ, et al. Calcitonin gene-related peptide: physiology and pathophysiology. Physiol Rev. 2014;94:1099–1142.
  • Olesen J, Diener HC, Husstedt IW, et al. Calcitonin gene-related peptide receptor antagonist BIBN 4096 BS for the acute treatment of migraine. N Engl J Med. 2004;350:1104–1110.
  • Ho TW, Ferrari MD, Dodick DW, et al. Efficacy and tolerability of MK-0974 (telcagepant), a new oral antagonist of calcitonin generelated peptide receptor, compared with zolmitriptan for acute migraine: a randomised, placebo-controlled, paralleltreatment trial. Lancet. 2008;372:2115–2123.
  • Min KC, Kraft WK, Bondiskey P, et al. Atogepant is not associated with clinically meaningful alanine aminotransferase elevations in healthy adults. Clin Transl Sci. 2020;14:599–605.
  • Goadsby PJ, Dodick DW, Ailani J, et al. Safety, tolerability, and efficacy of orally administered atogepant for the prevention of episodic migraine in adults: a double-blind, randomised phase 2b/3 trial. Lancet Neurol. 2020;19:727–737.
  • Zeller J, Poulsen KT, Sutton JE, et al. CGRP function-blocking antibodies inhibit neurogenic vasodilatation without affecting heart rate or arterial blood pressure in the rat. Br J Pharmacol. 2008;155:1093–1103.
  • MaassenVanDenBrink A, Meijer J, Villalón CM, et al. Wiping out CGRP: potential cardiovascular risks. Trends Pharmacol Sci. 2016;37:779–788.
  • Bigal ME, Walter S, Rapoport AM. Therapeutic antibodies against CGRP or its receptor. Br J Clin Pharmacol. 2015;79:886–895.
  • Juhl L, Edvinsson L, Olesen J, et al. Effect of two novel CGRP-binding compounds in a closed cranial window rat model. Eur J Pharmacol. 2007;567:117–124.
  • Kohler G, Milstein C. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature. 1975;256:495–497.
  • Castelli MS, McGonigle P, Hornby PJ. The pharmacology and therapeutic applications of monoclonal antibodies. Pharmacol Res Perpect. 2019;00:e00535.
  • Smith SL. Ten years of orthoclone OKT3 (Muromonab-CD3): a review. J Transpl Coord. 1996;6:109–121.
  • Wilde MI, Goa KL. Muromonab CD3: a reappraisal of its pharmacology and use as prophylaxis of solid organ transplant rejection. Drugs. 1996;51:865–894.
  • Antibody Society [Internet]. Framingham (MA): The antibody society; c2015. Antibody therapeutic approved or in regulatory review in the EU or US. [cited 2021 Apr 26]. Available from: https://www.antibodysociety.org/resources/approved-antibodies/
  • Janeway CA, Travers P, Walport M, et al. Immunobiology. 5th. New York (NY): Garland Science; 2001.
  • Singh S, Kumar N, Dwiwedi P, et al. Monoclonal antibodies: a review. Curr Clin Pharmacol. 2018;13:85-99.
  • Breedveld F. Therapeutic monoclonal antibodies. Lancet. 2000;355:735–740.
  • Taylor FR. CGRP, amylin, immunology, and headache medicine. Headache. 2019;59:131–150.
  • Shi L, Lehto SG, Zhu DX, et al. Pharmacologic characterization of AMG 334, a potent and selective human monoclonal antibody against the calcitonin gene-related peptide receptor. J Pharmacol Exp Ther. 2016;356:223–231.
  • Zeller J, Poulsen KT, Abdiche YN, et al. inventors; rinat neuroscience corp., assignee. Antagonist antibodies directed against calcitonin gene-related peptide and methods using same. Patent number: WO2007054809. 2007 May 18.
  • Benschop RJ, Gehlert DR, Merchant KM, et al. inventors; eli lilly co., assignee. Treatment of migraine with anti-CGRP antibodies. Patent number: WO2007076336 A1. 2007 July 5.
  • Garcia-Martinez LF, Kaiser EA, Kovacevich BR, et al. inventors; Alderbio Holdings Llc, The University of Iowa Research Foundation, assignee. Use of anti-cgrp antibodies and antibody fragments to prevent or inhibit photophobia or light aversion in subjects in need thereof, especially migraine sufferers. Patent number: WO2012162257A2. 2012 November 29
  • Vidarsson G, Dekkers G, Rispens T. IgG subclasses and allotypes: from structure to effector functions. Front Immunol. 2014;5:520.
  • Keizer R, Huitema A, Schellens J, et al. Clinical pharmacokinetics of therapeutic monoclonal antibodies. Clin Pharm. 2010;49:493–507.
  • Tjandra JJ, Ramadi L, McKenzie IF. Development of human anti-murine antibody (HAMA) response in patients. Immunol Cell Biol. 1990;68:367–376.
  • Jones PT, Dear PH, Foote J, et al. Replacing the complementarity-determining regions in a human antibody with those from a mouse. Nature. 1986;321:522–525.
  • Boulianne GL, Hozumi N and Shulman MJ. Production of functional chimaeric mouse/human antibody. Nature. 1984;312:643–646.
  • Foltz IN, Gunasekaran K and King CT. Discovery and biooptimization of human antibody therapeutics using the XenoMouse® transgenic mouse platform. Immunol Rev. 2016;270:51–64.
  • World Health Organization (Switzerland). International Nonproprietary Names (INN) for biological and biotechnological substances (a review). Publication of the WHO; 2019. [cited 2021 Apr 26]. Available from: https://www.who.int/medicines/services/inn/BioReview2019.pdf
  • Descotes J. Immunotoxicity of monoclonal antibodies. mAbs. 2009;1:104–111.
  • Silberstein SD, Lenz R, Xu C. Therapeutic monoclonal antibodies: What headache specialists need to know. Headache. 2015;55:1171–1182.
  • Mullard A. FDA drug approvals. Nat Rev Drug Discov. 2018;2019(18):85–89.
  • Diener HC, Marmura MJ, Tepper SJ, et al. Efficacy, tolerability, and safety of eptinezumab in patients with a dual diagnosis of chronic migraine and medication-overuse headache: Subgroup analysis of PROMISE-2. Headache. 2021;61:125–136.
  • Markham A. Erenumab: First global approval. Drugs. 2018;78:1157–1161.
  • Lipton RB, Tepper SJ, Reuter U, et al. Erenumab in chronic migraine: Patient-reported outcomes in a randomized double-blind study. Neurology. 2019;92:e2250–e2260.
  • Pavlovic JM, Paemeleire K, Göbel H, et al. Efficacy and safety of erenumab in women with a history of menstrual migraine. J Headache Pain. 2020;21:95.
  • Goadsby PJ, Reuter U, Hallström Y, et al. One-year sustained efficacy of erenumab in episodic migraine: Results of the STRIVE study. Neurology. 2020;95:e469–e479.
  • Ashina M, Goadsby PJ, Reuter U, et al. Long-term safety and tolerability of erenumab: Three-plus year results from a five-year open-label extension study in episodic migraine. Cephalalgia. 2019;39:1455–1464.
  • Xu Y, Gabriel K, Wang Y, et al. A multi-center, open-label, pharmacokinetic drug interaction study of erenumab and a combined oral contraceptive in healthy females. CNS Drugs. 2019;33:513–522.
  • Raffaelli B, Mussetto V, Israel H, et al. Erenumab and galcanezumab in chronic migraine prevention: effects after treatment termination. J Headache Pain. 2019;20:66.
  • Lamb YN. Galcanezumab: First global approval. Drugs. 2018;78:1769–1775.
  • 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;19:814–825.
  • Silberstein SD, Stauffer VL, Day KA, et al. Galcanezumab in episodic migraine: subgroup analyses of efficacy by high versus low frequency of migraine headaches in phase 3 studies (EVOLVE-1 & EVOLVE-2). J Headache Pain. 2019;20:75.
  • Stauffer VL, Turner I, Kemmer P, et al. Effect of age on pharmacokinetics, efficacy, and safety of galcanezumab treatment in adult patients with migraine: results from six phase 2 and phase 3 randomized clinical trials. J Headache Pain. 2020;21:79.
  • Hoy SM. Fremanezumab: first global approval. Drugs. 2018;78:1829–1834.
  • Silberstein SD, Dodick DW, Bigal ME, et al. Fremanezumab for the preventive treatment of chronic migraine. New Eng J Med. 2017;377:2113–2122.
  • Kuwasako K, Shimekake Y, Masuda M, et al. Visualization of the calcitonin receptor-like receptor and its receptor activity-modifying proteins during internalization and recycling. J Biol Chem. 2000;275:29602–29609.
  • Dhillon S. Eptinezumab: first approval. Drugs. 2020;80:733–739.
  • Ashina M, Saper J, Cady R, et al. Eptinezumab in episodic migraine: a randomized, double-blind, placebo-controlled study (PROMISE-1). Cephalalgia. 2020;40:241–254.
  • Lipton RB, Goadsby PJ, Smith J, et al. Efficacy and safety of eptinezumab in patients with chronic migraine: PROMISE-2. Neurology. 2020;94:e1365–e1377.
  • Silberstein S, Diamond M, Hindiyeh NA, et al. Eptinezumab for the prevention of chronic migraine: efficacy and safety through 24 weeks of treatment in the phase 3 PROMISE-2 (Prevention of migraine via intravenous ALD403 safety and efficacy-2) study. J Headache Pain. 2020;21:120.
  • Smith TR, Janelidze M, Chakhava G, et al. Eptinezumab for the prevention of episodic migraine: sustained effect through 1 year of treatment in the PROMISE-1 study. Clin Ther. 2020;42:2254–2265.e2253.
  • Grilo AL, Mantalaris A. The increasingly human and profitable monoclonal antibody market. Trends Biotechnol. 2019;37:9–16.
  • Urquhart L. Top drugs and companies by sales in 2018. Nat Rev Drug Discov. 2019;18:245.
  • Caskey M, Klein F, Nussenzweig MC. Broadly neutralizing anti-HIV-1 monoclonal antibodies in the clinic. Nat Med. 2019;25:547–553.
  • Fouladirad S, Bach H. Development of coronavirus treatments using neutralizing antibodies. Microorganisms. 2021;9:165.
  • Gklinos P, Papadopoulou M, Stanulovic V, et al. Monoclonal antibodies as neurological therapeutics. Pharmaceuticals. 2021;14:92.
  • Liu L. Antibody glycosylation and its impact on the pharmacokinetics and pharmacodynamics of monoclonal antibodies and Fc-fusion proteins. J Pharm Sci. 2015;104:1866–1884.
  • Kizhedath A, Wilkinson S, Glassey J. Applicability of predictive toxicology methods for monoclonal antibody therapeutics: status Quo and scope. Arch Toxicol. 2017;91:1595–1612.
  • Higel F, Sandl T, Kao CY, et al. N-glycans of complex glycosylated biopharmaceuticals and their impact on protein clearance. Eur J Pharm Biopharm. 2019;139:123–131.
  • Doevendans E, Schellekens H. Immunogenicity of innovative and biosimilar monoclonal antibodies. Antibodies. 2019;8:21.
  • Lin RY, Rodriguez-Baez G, Bhargave GA. Omalizumab-associated anaphylactic reactions reported between January 2007 and June 2008. Ann Allergy Asthma Immunol. 2009;103:442–445.
  • Strangfeld A, Listing J. Infection and musculoskeletal conditions: bacterial and opportunistic infections during anti-TNF therapy. Best Pract Res Clin Rheumatol. 2006;20:1181–1195.
  • Salvana EMT, Salata RA. Infectious complications associated with monoclonal antibodies and related small molecules. Clin Microbiol Rev. 2009;22:274–290.
  • Wimalawansa SJ. Amylin, calcitonin gene-related peptide, calcitonin, and adrenomedullin: a peptide superfamily. Crit Rev Neurobiol. 1997;11:167–239.
  • Ashina M, Hansen JM, Do TP, et al. Migraine and the trigeminovascular system - 40 years and counting. Lancet Neurol. 2019;18:795–804.
  • Bernstein C, Burstein R. Sensitization of the trigeminovascular pathway: perspective and implications to migraine pathophysiology. J Clin Neurol. 2012;8:89–99.
  • Tfelt-Hansen P, De Vries P, Saxena PR. Triptans in migraine: a comparative review of pharmacology, pharmacokinetics and efficacy. Drugs. 2000;60:1259–1287.
  • Hostetler ED, Joshi AD, Sanabria-Bohórquez S, et al. In vivo quantification of calcitonin gene-related peptide receptor occupancy by telcagepant in rhesus monkey and human brain using the positron emission tomography tracer [11C]MK-4232. J Pharmacol Exp Ther. 2013;347:478–486.
  • Schankin CJ, Maniyar FH, Seo Y, et al. Ictal lack of binding the brain parenchyma suggest integrity of the blood-brain barrier for 11C-dihydroergotamine during glyceryl trinitrate-induced migraine. Brain. 2016;139:1994–2001.
  • Edvinsson L. The trigeminovascular pathway: role of CGRP and CGRP receptors in migraine. Headache. 2017;57(S2):47–55.
  • Edvinsson L, Tfelt-Hansen P. The blood-brain barrier in migraine treatment. Cephalalgia. 2008;28:1245–1258.
  • Noseda R, Schain AJ, Melo-Carrillo A, et al. Fluorescently-labeled fremanezumab is distributed to sensory and autonomic ganglia and the dura but not to the brain of rats with uncompromised blood brain barrier. Cephalalgia. 2020;40:229–240.
  • Johnson KW, Morin SM, Wroblewski VJ, et al. Peripheral and central nervous system distribution of the CGRP neutralizing antibody [125I] galcanezumab in male rats. Cephalalgia. 2019;39:1241–1248.
  • Mallee JJ, Salvatore CA, LeBourdelles B, et al. Receptor activity-modifying protein 1 determines the species selectivity of nonpeptide CGRP receptor antagonists. J Biol Chem. 2002;277:14294–14298.
  • Garces F, Mohr C, Zhang L, et al. Molecular insight into recognition of the CGRPR complex by migraine prevention therapy Aimovig (erenumab). Cell Rep. 2020;30:1714.1723.
  • Bhakta M, Vuong T, Taura T, et al. Migraine therapeutics differentially modulate the CGRP pathway. Cephalalgia. 2021;41:499–514.
  • Gingell JJ, Hendrikse ER, Hay DL. New insights into the regulation of CGRP-family receptors. Trends Pharmacol Sci. 2019;40:71–83.
  • Hay DL, Walker CS. CGRP and its receptors. Headache. 2017;57:625–636.
  • Walker CS, Eftekhari S, Bower RL, et al. A second trigeminal CGRP receptor: Function and expression of the AMY1 receptor. Ann Clin Transl Neurol. 2015;2:595–608.
  • Garces F, Mohr C, Zhang L, et al. Molecular insight into recognition of the CGRPR complex by migraine prevention therapy Aimovig (erenumab). Cell Rep. 2020;30:17141723.
  • Boyle CN, Lutz TA, Le Foll C. Amylin – its role in the homeostatic and hedonic control of eating and recent developments of amylin analogs to treat obesity. Mol Metab. 2018;8:203–210.
  • Hay DL, Chen S, Lutz TA, et al. Amylin: Pharmacology, physiology, and clinical potential. Pharmacol Rev. 2015;67:564–600.
  • Sun H, Dodick DW, Silberstein S, et al. Safety and efficacy of AMG 334 for prevention of episodic migraine: a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Neurol. 2016;15:382–390.
  • Diener HC, Holle D, Solbach K, et al. Medication-over-use headache: Risk factors, pathophysiology and management. Nat Rev Neurol. 2016;12:575–583.
  • González-Hernández A, Marichal-Cancino BA, Lozano-Cuenca J, et al. Heteroreceptors modulating CGRP release at neurovascular junction: potential therapeutic implications on some vascular-related diseases. BioMed Res Int. 2016;2016:2056786.
  • De Boer I, MaassenVanDenBrink A, Terwindt GM. The potential danger of blocking CGRP for treating migraine in CADASIL patients. Cephalalgia. 2020;40:1676–1678.
  • Rubio-Beltrán E, Labastida-Ramírez A, Haanes KA, et al. Characterization of vasodilatory responses in presence of the CGRP receptor antibody erenumab in human isolated arteries. Cephalalgia. 2019;39:1735–1744.
  • Cohen JM, Ning X, Kessler Y, et al. Immunogenicity of biologic therapies for migraine: a review of current evidence. J Head Pain. 2021;22:1–8.
  • Dodick DW, Goadsby PJ, Spierings ELH, et al. Safety and efficacy of LY2951742, a monoclonal antibody to calcitonin gene-related peptide, for the prevention of migraine: a phase 2, randomised, double-blind, placebo-controlled study. Lancet Neurol. 2014;13:885–892.
  • Stauffer VL, Dodick DW, Zhang Q, et al. Evaluation of galcanezumab for the prevention of episodic migraine: the EVOLVE-1 randomized clinical trial. JAMA Neurol. 2018;75:1080–1088.
  • Dodick DW, Ashina M, Brandes JL, et al. ARISE: a phase 3 randomized trial of erenumab for episodic migraine. Cephalalgia. 2018;38:1026–1037.
  • Goadsby PJ, Reuter U, Hallstrom Y, et al. A controlled trial of erenumab for episodic migraine. N Engl J Med. 2017;377:2123–2132.
  • Dodick DW, Silberstein SD, Bigal ME, et al. Effect of fremanezumab compared with placebo for prevention of episodic migraine: a randomized clinical trial. JAMA. 2018;319:1999–2008.
  • Skljarevski V, Matharu M, Millen BA, et al. Efficacy and safety of galcanezumab for the prevention of episodic migraine: Results of the EVOLVE-2 Phase 3 randomized controlled clinicaltrial. Cephalalgia. 2018;38:1442–1454.
  • Detke HC, Goadsby PJ, Wang S, et al. Galcanezumab in chronic migraine. The randomized, double-blind, placebo-controlled REGAIN study. Neurology. 2018;99:e2211–e2221.
  • Tepper S, Ashina M, Reuter U, et al. Safety and efficacy of erenumab for preventive treatment of chronic migraine: a randomised, double-blind, placebo-controlled phase 2 trial. Lancet Neurol. 2017;16:425–434.
  • Tepper SJ, Diener HC, Ashina M, et al. Erenumab in chronic migraine with medication overuse: subgroup analysis of a randomized trial. Neurology. 2019;92:e2309–e2320.
  • Charles A, Pozo-Rosich P. Targeting calcitonin gene-related peptide: a new era in migraine therapy. Lancet. 2019;394:1765–1774.
  • Ament M, Day K, Stauffer VL, et al. Effect of galcanezumab on severity and symptoms of migraine in phase 3 trials in patients with episodic or chronic migraine. J Head Pain. 2021;22:1–10.
  • Kuruppu DK, North JM, Kovacik AJ, et al. Onset, maintenance, and cessation of effect of galcanezumab for prevention of migraine: a narrative review of three randomized placebo-controlled trials. Adv Ther. 2021;38:1614–1626.
  • Tfelt-Hansen P, Diener HC, Steiner TJ. Problematic presentation and use of efficacy measures in current trials of CGRP monoclonal antibodies for episodic migraine prevention: a mini-review. Cephalalgia. 2020;40:122–126.
  • Drellia K, Kokoti L, Deligianni CI, et al. Anti-CGRP monoclonal antibodies for migraine prevention: a systematic review and likelihood to help or harm analysis. Cephalalgia. 2021;41:851–864.
  • Schytz HW, Birk S, Wienecke T, et al. PACAP38 induces migraine-like attacks in patients with migraine without aura. Brain. 2009;132(Pt 1):16–25.
  • Zagami AS, Edvinsson L, Goadsby PJ. Pituitary adenylate cyclase activating polypeptide and migraine. Ann Clin Transl Neurol. 2014;1:1036–1040.
  • Amin FM, Hougaard A, Schytz HW, et al. Investigation of the pathophysiological mechanisms of migraine attacks induced by pituitary adenylate cyclase-activating polypeptide-38. Brain. 2014;137:779–794.
  • Ashina M, Doležil D, Bonner JH, et al. A phase 2, randomized, double-blind, placebo-controlled trial of AMG 301, a pituitary adenylate cyclase-activating polypeptide PAC1 receptor monoclonal antibody for migraine prevention. Cephalalgia. 2021;41:33–44.
  • Hoffmann J, Miller S, Martins-Oliveira M, et al. PAC1 receptor blockade reduces central nociceptive activity: new approach for primary headache? Pain. 2020;161:1670–1681.
  • Ashina H, Guo S, Vollesen ALH, et al. PACAP38 in human models of primary headaches. J Headache Pain. 2017;18:110.
  • Moldovan-Loomis C, Dutzar B, Ojala EW, et al. Pharmacologic characterization of ALD1910, a potent humanized monoclonal antibody against the pituitary adenylate cyclase-activating peptide. J Pharmacol Exp Ther. 2019;369:26–36.
  • Birk S, Sitarz JT, Petersen KA, et al. The effect of intravenous PACAP38 on cerebral hemodynamics in healthy volunteers. Regul Pept. 2007;140:185–191.
  • Rustichelli C, Lo Castro F, Baraldi C, et al. Targeting pituitary adenylate cyclase-activating polypeptide (PACAP) with monoclonal antibodies in migraine prevention: a brief review. Expert Opin Investig Drugs. 2020;29:1269–1275.
  • Burstein R, Noseda R, Borsook D. Migraine: multiple processes, complex pathophysiology. J Neurosci. 2015;35:6619–6629.
  • Goadsby PJ, Holland PR, Martins-Oliveira M, et al. Pathophysiology of migraine: a disorder of sensory processing. Physiol Rev. 2017;97:553–622.
  • Becker WJ. Acute migraine treatment in adults. Headache. 2015;55:778–793.
  • Lipton RB, Silberstein SD. Episodic and chronic migraine headache: breaking down barriers to optimal treatment and prevention. Headache. 2015;55(S2):103–122.
  • Orlando V, Mucherino S, Monetti VM, et al. Treatment patterns and medication adherence among newly diagnosed patients with migraine: a drug utilisation study. BMJ Open. 2020;10:e038972.
  • MacGregor EA, Evers S, International Headache Society. The role of methysergide in migraine and cluster headache treatment worldwide - A survey in members of the international headache society. Cephalalgia. 2017;37:1106–1108.
  • Rapoport AM, McAllister P. The headache pipeline: excitement and uncertainty. Headache. 2020;60:190–199.
  • Pringsheim T, Davenport W, Mackie G, et al. Canadian headache society guideline for migraine prophylaxis. Can J Neurol Sci. 2012 Mar;39(2 Suppl 2):S1–59.
  • Becerra L, Bishop J, Barmettler G, et al. Triptans disrupt brain networks and promote stress-induced CSD-like responses in cortical and subcortical areas. J Neurophysiol. 2016;115:208–217.
  • Schwedt TJ, Chong CD. Medication overuse headache: pathophysiological insights from structural and functional brain MRI research. Headache. 2017;57:1173–1178.
  • Saengjaroentham C, Strother LC, Dripps I, et al. Differential medication overuse risk of novel antimigraine therapeutics. Brain. 2020;143:2681–2688.
  • Schain AJ, Melo-Carrillo A, Stratton J, et al. CSD-induced arterial dilatation and plasma protein extravasation are unaffected by fremanezumab: implications for CGRP’s role in migraine with aura. J Neurosci. 2019;39:6001–6011.
  • Melo-Carrillo A, Schain AJ, Stratton J, et al. Fremanezumab and its isotype slow propagation rate and shorten cortical recovery period but do not prevent occurrence of cortical spreading depression in rats with compromised blood-brain barrier. Pain. 2020;161:1037–1043.
  • Akerman S, Holland PR, Goadsby PJ. Diencephalic and brainstem mechanisms in migraine. Nat Rev Neurosci. 2011;12:570–584.
  • Ashina M, Hansen JM, Do TP, et al. Migraine and the trigeminovascular system-40 years and counting. Lancet Neurol. 2019;18:795–804.
  • Edvinsson JCA, Viganò A, Alekseeva A, et al. The fifth cranial nerve in headaches. J Headache Pain. 2020 Jun;5(21):65.
  • Edvinsson JCA, Warfvinge K, Krause DN, et al. C-fibers may modulate adjacent Aδ-fibers through axon-axon CGRP signaling at nodes of Ranvier in the trigeminal system. J Headache Pain. 2019;20:105.
  • Melo-Carrillo A, Strassman AM, Nir RR, et al. Fremanezumab-A humanized monoclonal anti-CGRP antibody-inhibits thinly myelinated (Aδ) but not unmyelinated (C) meningeal nociceptors. J Neurosci. 2017;37:10587–10596.
  • Ohlsson L, Kronvall E, Stratton J, et al. Fremanezumab blocks CGRP induced dilatation in human cerebral, middle meningeal and abdominal arteries. J Headache Pain. 2018;19:66.
  • Deen M, Correnti E, Kamm K, et al. Blocking CGRP in migraine patients - a review of pros and cons. J Headache Pain. 2017;18:96.
  • Haanes KA, Edvinsson L, Sams A. Understanding side-effects of anti-CGRP and anti-CGRP receptor antibodies. J Headache Pain. 2020;21:26.
  • Kashem SW, Riedl MS, Yao C, et al. Nociceptive sensory fibers drive Interleukin-23 production from CD301b+ dermal dendritic cells and drive protective cutaneous immunity. Immunity. 2015;43:515–526.
  • Joshi N, McAree M, Klimowich K, et al. Oral candidiasis in a migraine patient taking erenumab and galcanezumab: a case report. SN Compreh Clin Med. 2020;2:658–661.
  • Hou M, Xing H, Cai Y, et al. The effect and safety of monoclonal antibodies to calcitonin gene-related peptide and its receptor on migraine: a systematic review and meta-analysis. J Headache Pain. 2017;18:42.
  • Spierings ELH, Kärppä M, Ning X, et al. Efficacy and safety of fremanezumab in patients with migraine and inadequate response to prior preventive treatment: subgroup analyses by country of a randomized, placebo-controlled trial. J Headache Pain. 2021;22:26.
  • Cohen-Barak O, Weiss S, Rasamoelisolo M, et al. A phase 1 study to assess the pharmacokinetics, safety, and tolerability of fremanezumab doses (225 mg, 675 mg and 900 mg) in Japanese and Caucasian healthy subjects. Cephalalgia. 2018;38:1960–1971.
  • Kielbasa W, O’Brien L, Moser B, et al. Assessment of pharmacokinetics, target engagement and immunogenicity in patients with migraine administered galcanezumab, an anti-CGRP antibody. Headache. 2018;58(S2):77–78.
  • Baker B, Schaeffler B, Beliveau M, et al. Population pharmacokinetics of eptinezumab for the preventive treatment of migraine. Cephalalgia. 2019;39(S1):37.
  • de Hoon J, Van Hecken A, Vandermeulen C, et al. Phase I, randomized, double-blind, placebo-controlled, single-dose, and multiple-dose studies of erenumab in healthy subjects and patients with migraine. Clin Pharmacol Ther. 2018;103:815–825.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.