Calcitonin Gene-Related Peptide Monoclonal Antibodies for Cluster Headache

Main Article Content

Robyn Jenia Wilcha Peter J. Goadsby

Abstract

Cluster headache is a disabling neurologic disorder that is characterized by daily, attacks of very severe, strictly unilateral pain occurring over a period of weeks or months. Recently, calcitonin gene-related peptide and its receptor complex have garnered attention as promising targets for treating primary headache disorders: particularly migraine and cluster headache. Calcitonin gene-related peptide is found in the trigeminal sensory innervation of major cerebral vessels thought to carry nociceptive information during a headache. Increased levels of calcitonin gene-related peptide have been seen in the ipsilateral jugular venous outflow during an attack phase, and indeed, calcitonin gene-related peptide itself can trigger an attack if administered to a patient in bout, suggesting its distinct role in the generation of attacks. Various monoclonal antibodies targeting calcitonin gene-related peptide and its receptor are emerging as a new frontier in migraine with potential further therapeutic use in cluster headache. This review summarizes the current therapeutic approaches of cluster headache before sharing the potential future role of calcitonin gene-related peptide and its relevance in cluster headache pathology and as targets for future treatment.

Article Details

How to Cite
WILCHA, Robyn Jenia; GOADSBY, Peter J.. Calcitonin Gene-Related Peptide Monoclonal Antibodies for Cluster Headache. Medical Research Archives, [S.l.], v. 12, n. 6, june 2024. ISSN 2375-1924. Available at: <https://esmed.org/MRA/mra/article/view/5544>. Date accessed: 22 july 2024. doi: https://doi.org/10.18103/mra.v12i6.5544.
Section
Research Articles

References

1. Fischera M, Marziniak M, Gralow I, Evers S. The incidence and prevalence of cluster headache: a meta-analysis of population-based studies. Cephalalgia. 2008;28(6):614-8.

2. Steinberg A, Josefsson P, Alexanderson K, Sjostrand C. Cluster headache: Prevalence, sickness absence, and disability pension in working ages in Sweden. Neurology. 2019;93 (4):e404-e13.

3. Hagen K. One-year prevalence of cluster headache, hemicrania continua, paroxysmal hemicrania and SUNCT in Norway: a population-based nationwide registry study. J Headache Pain. 2024;25(1):30.

4. Headache Classification Committee of the International Headache Society (IHS) The International Classification of Headache Disorders, 3rd edition. Cephalalgia. 2018;38 (1):1-211.

5. Jensen RM, Lyngberg A, Jensen RH. Burden of cluster headache. Cephalalgia. 2007;27(6):535-41.

6. Jurgens TP, Gaul C, Lindwurm A, Dresler T, Paelecke-Habermann Y, Schmidt-Wilcke T, et al. Impairment in episodic and chronic cluster headache. Cephalalgia. 2011;31(6):671-82.

7. Trejo-Gabriel-Galan JM, Aicua-Rapun I, Cubo-Delgado E, Velasco-Bernal C. Suicide in primary headaches in 48 countries: A physician-survey based study. Cephalalgia. 2018;38(4): 798-803.

8. Wei DY, Khalil M, Goadsby PJ. Managing cluster headache. Pract Neurol. 2019;19(6):521-8.

9. Edvinsson L. Blockade of CGRP receptors in the intracranial vasculature: a new target in the treatment of headache. Cephalalgia. 2004;24(8):611-22.

10. Amara SG, Jonas V, Rosenfeld MG, Ong ES, Evans RM. Alternative RNA processing in calcitonin gene expression generates mRNAs encoding different polypeptide products. Nature. 1982;298(5871):240-4.

11. Carmine Belin A, Ran C, Edvinsson L. Calcitonin Gene-Related Peptide (CGRP) and Cluster Headache. Brain Sci. 2020;10(1).

12. Ho TW, Edvinsson L, Goadsby PJ. CGRP and its receptors provide new insights into migraine pathophysiology. Nat Rev Neurol. 2010;6(10):573-82.

13. Steenbergh PH, Hoppener JW, Zandberg J, Visser A, Lips CJ, Jansz HS. Structure and expression of the human calcitonin/CGRP genes. FEBS Lett. 1986;209(1):97-103.

14. Amara SG, Arriza JL, Leff SE, Swanson LW, Evans RM, Rosenfeld MG. Expression in brain of a messenger RNA encoding a novel neuropeptide homologous to calcitonin gene-related peptide. Science. 1985;229 (4718):1094-7.

15. Wimalawansa SJ, Morris HR, Etienne A, Blench I, Panico M, MacIntyre I. Isolation, purification and characterization of beta-hCGRP from human spinal cord. Biochem Biophys Res Commun. 1990;167(3):993-1000.

16. Lou H, Gagel RF. Alternative RNA processing--its role in regulating expression of calcitonin/calcitonin gene-related peptide. J Endocrinol. 1998;156(3):401-5.

17. Pellesi L DIR, Al-Karagholi MA, Ashina M.. Reducing Episodic Cluster Headaches: Focus on Galcanezumab. Journal of Pain Research. 2020;13:1591-1599.

18. Goadsby PJ, Edvinsson L. Human in vivo evidence for trigeminovascular activation in cluster headache. Neuropeptide changes and effects of acute attacks therapies. Brain. 1994;117 ( Pt 3):427-34.

19. Fanciullacci M, Alessandri M, Figini M, Geppetti P, Michelacci S. Increase in plasma calcitonin gene-related peptide from the extracerebral circulation during nitroglycerin-induced cluster headache attack. Pain. 1995;60(2):119-23.

20. Vollesen ALH, Snoer A, Beske RP, Guo S, Hoffmann J, Jensen RH, Ashina M. Effect of Infusion of Calcitonin Gene-Related Peptide on Cluster Headache Attacks: A Randomized Clinical Trial. JAMA Neurol. 2018;75(10): 1187-97.

21. Diener HC, May A. Drug Treatment of Cluster Headache. Drugs. 2022;82(1):33-42.

22. May A, Evers S, Goadsby PJ, Leone M, Manzoni GC, Pascual J, et al. European Academy of Neurology guidelines on the treatment of cluster headache. Eur J Neurol. 2023;30(10):2955-79.

23. Wei DY, Goadsby PJ. Recent Advances and Updates in Trigeminal Autonomic Cephalalgias. Semin Neurol. 2022;42(4):474-8.

24. Kudrow L. Response of cluster headache attacks to oxygen inhalation. Headache. 1981; 21(1):1-4.

25. Cohen AS, Burns B, Goadsby PJ. High-flow oxygen for treatment of cluster headache: a randomized trial. JAMA. 2009;302(22):2451-7.

26. Ekbom K, Monstad I, Prusinski A, Cole JA, Pilgrim AJ, Noronha D. Subcutaneous sumatriptan in the acute treatment of cluster headache: a dose comparison study. The Sumatriptan Cluster Headache Study Group. Acta Neurol Scand. 1993;88(1):63-9.

27. van Vliet JA, Bahra A, Martin V, Ramadan N, Aurora SK, Mathew NT, et al. Intranasal sumatriptan in cluster headache: randomized placebo-controlled double-blind study. Neurology. 2003;60(4):630-3.

28. Cittadini E, May A, Straube A, Evers S, Bussone G, Goadsby PJ. Effectiveness of intranasal zolmitriptan in acute cluster headache: a randomized, placebo-controlled, double-blind crossover study. Arch Neurol. 2006;63(11):1537-42.

29. Rapoport AM, Mathew NT, Silberstein SD, Dodick D, Tepper SJ, Sheftell FD, Bigal ME. Zolmitriptan nasal spray in the acute treatment of cluster headache: a double-blind study. Neurology. 2007;69(9):821-6.

30. Bahra A, Gawel MJ, Hardebo JE, Millson D, Breen SA, Goadsby PJ. Oral zolmitriptan is effective in the acute treatment of cluster headache. Neurology. 2000;54(9):1832-9.

31. Reuter U, McClure C, Liebler E, Pozo-Rosich P. Non-invasive neuromodulation for migraine and cluster headache: a systematic review of clinical trials. J Neurol Neurosurg Psychiatry. 2019;90(7):796-804.

32. Silberstein SD, Mechtler LL, Kudrow DB, Calhoun AH, McClure C, Saper JR, et al. Non-Invasive Vagus Nerve Stimulation for the ACute Treatment of Cluster Headache: Findings From the Randomized, Double-Blind, Sham-Controlled ACT1 Study. Headache. 2016;56 (8):1317-32.

33. Goadsby PJ, de Coo IF, Silver N, Tyagi A, Ahmed F, Gaul C, et al. Non-invasive vagus nerve stimulation for the acute treatment of episodic and chronic cluster headache: A randomized, double-blind, sham-controlled ACT2 study. Cephalalgia. 2018;38(5):959-69.

34. Schor LI, Pearson SM, Shapiro RE, Zhang W, Miao H, Burish MJ. Cluster headache epidemiology including pediatric onset, sex, and ICHD criteria: Results from the International Cluster Headache Questionnaire. Headache. 2021;61(10):1511-20.

35. Leone M, D'Amico D, Frediani F, Moschiano F, Grazzi L, Attanasio A, Bussone G. Verapamil in the prophylaxis of episodic cluster headache: a double-blind study versus placebo. Neurology. 2000;54(6):1382-5.

36. Tfelt-Hansen P, Tfelt-Hansen J. Verapamil for cluster headache. Clinical pharmacology and possible mode of action. Headache. 2009;49(1):117-25.

37. Matharu MS, van Vliet JA, Ferrari MD, Goadsby PJ. Verapamil induced gingival enlargement in cluster headache. J Neurol Neurosurg Psychiatry. 2005;76(1):124-7.

38. Cohen AS, Matharu MS, Goadsby PJ. Electrocardiographic abnormalities in patients with cluster headache on verapamil therapy. Neurology. 2007;69(7):668-75.

39. Lanteri-Minet M, Silhol F, Piano V, Donnet A. Cardiac safety in cluster headache patients using the very high dose of verapamil (>/=720 mg/day). J Headache Pain. 2011;12(2):173-6.

40. Bussone G, Leone M, Peccarisi C, Micieli G, Granella F, Magri M, et al. Double blind comparison of lithium and verapamil in cluster headache prophylaxis. Headache. 1990;30(7): 411-7.

41. BNF: Topiramate: National Institute for Health and Care Excellence (NICE): British National Formulary (BNF); [Available from: https://bnf.nice.org.uk/drugs/topiramate/

42. Jammes JL. The treatment of cluster headaches with prednisone. Dis Nerv Syst. 1975;36(7):375-6.

43. Antonaci F, Costa A, Candeloro E, Sjaastad O, Nappi G. Single high-dose steroid treatment in episodic cluster headache. Cephalalgia. 2005;25(4):290-5.

44. Obermann M, Nagel S, Ose C, Sonuc N, Scherag A, Storch P, et al. Safety and efficacy of prednisone versus placebo in short-term prevention of episodic cluster headache: a multicentre, double-blind, randomised controlled trial. Lancet Neurol. 2021;20(1):29-37.

45. Gordon A, Roe T, Villar-Martinez MD, Moreno-Ajona D, Goadsby PJ, Hoffmann J. Effectiveness and safety profile of greater occipital nerve blockade in cluster headache: a systematic review. J Neurol Neurosurg Psychiatry. 2023;95(1):73-85.

46. Barbanti P, Aurilia C, Fofi L, Egeo G, Ferroni P. The role of anti-CGRP antibodies in the pathophysiology of primary headaches. Neurol Sci. 2017;38(Suppl 1):31-5.

47. Goadsby PJ, Dodick DW, Leone M, Bardos JN, Oakes TM, Millen BA, et al. Trial of Galcanezumab in Prevention of Episodic Cluster Headache. New England Journal of Medicine. 2019;381(2):132-41.

48. Dodick DW, Goadsby PJ, Lucas C, Jensen R, Bardos JN, Martinez JM, et al. Phase 3 randomized, placebo-controlled study of galcanezumab in patients with chronic cluster headache: Results from 3-month double-blind treatment. Cephalalgia. 2020;40(9):935-48.

49. Lipton RB DH, Barbanti P, Schiemann J, Barash S, Cohen JM, et al. Efficacy and safety of fremanezumab for the prevention of episodic cluster headache: results of a randomized, double-blind, placebo-controlled, phase 3 study. Cephalalgia. 2019;39(1S):358-9.

50. Russell FA, King R, Smillie SJ, Kodji X, Brain SD. Calcitonin gene-related peptide: physiology and pathophysiology. Physiol Rev. 2014;94(4):1099-142.

51. Eftekhari S, Warfvinge K, Blixt FW, Edvinsson L. Differentiation of nerve fibers storing CGRP and CGRP receptors in the peripheral trigeminovascular system. J Pain. 2013;14(11):1289-303.

52. Lundberg JM, Franco-Cereceda A, Hua X, Hokfelt T, Fischer JA. Co-existence of substance P and calcitonin gene-related peptide-like immunoreactivities in sensory nerves in relation to cardiovascular and bronchoconstrictor effects of capsaicin. Eur J Pharmacol. 1985;108(3):315-9.

53. Frederiksen SD, Warfvinge K, Ohlsson L, Edvinsson L. Expression of Pituitary Adenylate Cyclase-activating Peptide, Calcitonin Gene-related Peptide and Headache Targets in the Trigeminal Ganglia of Rats and Humans. Neuroscience. 2018;393:319-32.

54. Karsan N, Goadsby PJ. Calcitonin gene-related peptide and migraine. Curr Opin Neurol. 2015;28(3):250-4.

55. Warfvinge K, Edvinsson L. Distribution of CGRP and CGRP receptor components in the rat brain. Cephalalgia. 2019;39(3):342-53.

56. O'Connor TP, van der Kooy D. Enrichment of a vasoactive neuropeptide (calcitonin gene related peptide) in the trigeminal sensory projection to the intracranial arteries. J Neurosci. 1988;8(7):2468-76.

57. O'Connor TP, van der Kooy D. Pattern of intracranial and extracranial projections of trigeminal ganglion cells. J Neurosci. 1986;6 (8):2200-7.

58. Iannone LF, De Logu F, Geppetti P, De Cesaris F. The role of TRP ion channels in migraine and headache. Neurosci Lett. 2022; 768:136380.

59. Benarroch EE. CGRP: sensory neuropeptide with multiple neurologic implications. Neurology. 2011;77(3):281-7.

60. Escott KJ, Brain SD. Effect of a calcitonin gene-related peptide antagonist (CGRP8-37) on skin vasodilatation and oedema induced by stimulation of the rat saphenous nerve. Br J Pharmacol. 1993;110(2):772-6.

61. Iyengar S, Johnson KW, Ossipov MH, Aurora SK. CGRP and the Trigeminal System in Migraine. Headache. 2019;59(5):659-81.

62. Goadsby PJ, Hoskin KL. The distribution of trigeminovascular afferents in the nonhuman primate brain Macaca nemestrina: a c-fos immunocytochemical study. J Anat. 1997;190 ( Pt 3)(Pt 3):367-75.

63. Meng J, Wang J, Lawrence G, Dolly JO. Synaptobrevin I mediates exocytosis of CGRP from sensory neurons and inhibition by botulinum toxins reflects their anti-nociceptive potential. J Cell Sci. 2007;120(Pt 16):2864-74.

64. O'Connell JP, Kelly SM, Raleigh DP, Hubbard JAM, Price NC, Dobson CM, Smith BJ. On the role of the C-terminus of α-calcitonin-gene-related peptide (αCGRP). The structure of des-phenylalaninamide37-αCGRP and its interaction with the CGRP receptor. Biochemical Journal. 1993;291(1):205-10.

65. Goadsby PJ, Holland PR, Martins-Oliveira M, Hoffmann J, Schankin C, Akerman S. Pathophysiology of Migraine: A Disorder of Sensory Processing. Physiol Rev. 2017;97(2): 553-622.

66. Walker CS, Raddant AC, Woolley MJ, Russo AF, Hay DL. CGRP receptor antagonist activity of olcegepant depends on the signalling pathway measured. Cephalalgia. 2018;38(3):437-51.

67. Hay DL, Poyner DR, Smith DM. Desensitisation of adrenomedullin and CGRP receptors. Regul Pept. 2003;112(1-3):139-45.

68. Evans BN, Rosenblatt MI, Mnayer LO, Oliver KR, Dickerson IM. CGRP-RCP, a novel protein required for signal transduction at calcitonin gene-related peptide and adrenomedullin receptors. J Biol Chem. 2000;275(40):31438-43.

69. Hoare SR. Mechanisms of peptide and nonpeptide ligand binding to Class B G-protein-coupled receptors. Drug Discov Today. 2005;10(6):417-27.

70. Weston C, Winfield I, Harris M, Hodgson R, Shah A, Dowell SJ, et al. Receptor Activity-modifying Protein-directed G Protein Signaling Specificity for the Calcitonin Gene-related Peptide Family of Receptors. J Biol Chem. 2016;291(42):21925-44.

71. Edvinsson L, Fredholm BB, Hamel E, Jansen I, Verrecchia C. Perivascular peptides relax cerebral arteries concomitant with stimulation of cyclic adenosine monophosphate accumulation or release of an endothelium-derived relaxing factor in the cat. Neurosci Lett. 1985;58(2):213-7.

72. Nelson MT, Huang Y, Brayden JE, Hescheler J, Standen NB. Arterial dilations in response to calcitonin gene-related peptide involve activation of K+ channels. Nature. 1990;344(6268):770-3.

73. Brain SD, Grant AD. Vascular actions of calcitonin gene-related peptide and adrenomedullin. Physiol Rev. 2004;84(3):903-34.

74. Gray DW, Marshall I. Human alpha-calcitonin gene-related peptide stimulates adenylate cyclase and guanylate cyclase and relaxes rat thoracic aorta by releasing nitric oxide. Br J Pharmacol. 1992;107(3):691-6.

75. Queen LR, Xu B, Horinouchi K, Fisher I, Ferro A. beta(2)-adrenoceptors activate nitric oxide synthase in human platelets. Circ Res. 2000;87(1):39-44.

76. Ferro A, Queen LR, Priest RM, Xu B, Ritter JM, Poston L, Ward JP. Activation of nitric oxide synthase by beta 2-adrenoceptors in human umbilical vein endothelium in vitro. Br J Pharmacol. 1999;126(8):1872-80.

77. Goadsby PJ. Effect of stimulation of facial nerve on regional cerebral blood flow and glucose utilization in cats. Am J Physiol. 1989;257(3 Pt 2):R517-21.

78. Goadsby PJ, Shelley S. High-frequency stimulation of the facial nerve results in local cortical release of vasoactive intestinal polypeptide in the anesthetised cat. Neurosci Lett. 1990;112(2-3):282-9.

79. Goadsby PJ, Lambert GA, Lance JW. The peripheral pathway for extracranial vasodilatation in the cat. J Auton Nerv Syst. 1984;10(2):145-55.

80. Goadsby PJ, Lipton RB. A review of paroxysmal hemicranias, SUNCT syndrome and other short-lasting headaches with autonomic feature, including new cases. Brain. 1997;120 (Pt 1):193-209.

81. Spencer SE, Sawyer WB, Wada H, Platt KB, Loewy AD. CNS projections to the pterygopalatine parasympathetic preganglionic neurons in the rat: a retrograde transneuronal viral cell body labeling study. Brain Res. 1990; 534(1-2):149-69.

82. Knight YE CJ, Kowacs F, Goadsby PJ. Fos expression in the midbrain periaqueductal grey after trigeminovascular stimulation. Cephalalgia. 2001;2001;21(401):50.

83. Goadsby PJ. Pathophysiology of cluster headache: a trigeminal autonomic cephalgia. Lancet Neurol. 2002;1(4):251-7.

84. Buzzi MG, Carter WB, Shimizu T, Heath H, 3rd, Moskowitz MA. Dihydroergotamine and sumatriptan attenuate levels of CGRP in plasma in rat superior sagittal sinus during electrical stimulation of the trigeminal ganglion. Neuropharmacology. 1991;30(11):1193-200.

85. Eftekhari S, Edvinsson L. Calcitonin gene-related peptide (CGRP) and its receptor components in human and rat spinal trigeminal nucleus and spinal cord at C1-level. BMC Neurosci. 2011;12:112.

86. Miller S, Liu H, Warfvinge K, Shi L, Dovlatyan M, Xu C, Edvinsson L. Immunohistochemical localization of the calcitonin gene-related peptide binding site in the primate trigeminovascular system using functional antagonist antibodies. Neuroscience. 2016;328:165-83.

87. Csati A, Tajti J, Tuka B, Edvinsson L, Warfvinge K. Calcitonin gene-related peptide and its receptor components in the human sphenopalatine ganglion -- interaction with the sensory system. Brain Res. 2012;1435:29-39.

88. Schoenen J, Jensen RH, Lanteri-Minet M, Lainez MJ, Gaul C, Goodman AM, et al. Stimulation of the sphenopalatine ganglion (SPG) for cluster headache treatment. Pathway CH-1: a randomized, sham-controlled study. Cephalalgia. 2013;33(10):816-30.

89. Snoer A, Vollesen ALH, Beske RP, Guo S, Hoffmann J, Fahrenkrug J, et al. Calcitonin-gene related peptide and disease activity in cluster headache. Cephalalgia. 2019;39(5): 575-84.

90. Walsh DA, Mapp PI, Kelly S. Calcitonin gene-related peptide in the joint: contributions to pain and inflammation. Br J Clin Pharmacol. 2015;80(5):965-78.

91. Geppetti P, Fusco BM, Marabini S, Maggi CA, Fanciullacci M, Sicuteri F. Secretion, pain and sneezing induced by the application of capsaicin to the nasal mucosa in man. Br J Pharmacol. 1988;93(3):509-14.

92. Geber C, Fondel R, Kramer HH, Rolke R, Treede RD, Sommer C, Birklein F. Psychophysics, flare, and neurosecretory function in human pain models: capsaicin versus electrically evoked pain. J Pain. 2007;8(6):503-14.

93. Amann R. Desensitization of capsaicin-evoked neuropeptide release--influence of Ca2+ and temperature. Naunyn Schmiedebergs Arch Pharmacol. 1990;342(6):671-6.

94. Zhou Y, Long H, Ye N, Liao L, Yang X, Jian F, et al. The effect of capsaicin on expression patterns of CGRP in trigeminal ganglion and trigeminal nucleus caudalis following experimental tooth movement in rats. J Appl Oral Sci. 2016;24(6):597-606.

95. Benschop RJ, Collins EC, Darling RJ, Allan BW, Leung D, Conner EM, et al. Development of a novel antibody to calcitonin gene-related peptide for the treatment of osteoarthritis-related pain. Osteoarthritis Cartilage. 2014;22(4):578-85.

96. Hoffmann J, May A. Diagnosis, pathophysiology, and management of cluster headache. Lancet Neurol. 2018;17(1):75-83.

97. Lipton RB, Micieli G, Russell D, Solomon S, Tfelt-Hansen P, Waldenlind E. Guidelines for controlled trials of drugs in cluster headache. Cephalalgia. 1995;15(6):452-62.

98. Kudrow D, Andrews JS, Rettiganti M, Oakes T, Bardos J, Gaul C, et al. Treatment Outcomes in Patients Treated With Galcanezumab vs Placebo: Post Hoc Analyses From a Phase 3 Randomized Study in Patients With Episodic Cluster Headache. Headache. 2020;60(10):2254-64.

99. Edvinsson L, Haanes KA, Warfvinge K, Krause DN. CGRP as the target of new migraine therapies - successful translation from bench to clinic. Nat Rev Neurol. 2018;14(6):338-50.

100. Felgenhauer K. Protein size and cerebrospinal fluid composition. Klin Wochenschr. 1974;52(24):1158-64.

101. Johnson KW, Morin SM, Wroblewski VJ, Johnson MP. Peripheral and central nervous system distribution of the CGRP neutralizing antibody [(125)I] galcanezumab in male rats. Cephalalgia. 2019;39(10):1241-8.

102. Rorabaugh J BJ, Hellriegel E, Ghibellini G, Zeng H, Lu X, et al. CNS target engagement by the anti-CGRP mAb fremanezumab in the cerebrospinal fluid of healthy volunteers. Cephalalgia. 2023;43(1S):1-2.

103. Mitsikostas DD, Edvinsson L, Jensen RH, Katsarava Z, Lampl C, Negro A, et al. Refractory chronic cluster headache: a consensus statement on clinical definition from the European Headache Federation. J Headache Pain. 2014;15(1):79.

104. de Coo IF, Marin JC, Silberstein SD, Friedman DI, Gaul C, McClure CK, et al. Differential efficacy of non-invasive vagus nerve stimulation for the acute treatment of episodic and chronic cluster headache: A meta-analysis. Cephalalgia. 2019;39(8):967-77.

105. Mo H, Kim BK, Moon HS, Cho SJ. Real-world experience with 240 mg of galcanezumab for the preventive treatment of cluster headache. J Headache Pain. 2022;23 (1):132.

106. Bigal ME, Walter S, Rapoport AM. Fremanezumab as a preventive treatment for episodic and chronic migraine. Expert Rev Neurother. 2019;19(8):719-28.

107. Teva stops fremanezumab development in cluster headache Clinical Trials Arena2019 [Available from:
https://www.clinicaltrialsarena.com/news/teva-fremanezumab-cluster-headache/?cf-view.

108. Kashiwagi K, Katsuki M, Kawamura S, Tachikawa S, Ono A, Koh A. Fremanezumab and Non-High-Dose Galcanezumab for Comorbid Cluster Headache in Patients with Migraine: Three Cases. Neurol Int. 2023;15(1): 318-24.

109. Shi L, Lehto SG, Zhu DX, Sun H, Zhang J, Smith BP, 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(1):223-31.

110. Riederer F, Wenner AM. Erenumab for chronic cluster headache: A case report. Cephalalgia Reports. 2020;3.

111. Silvestro M, Tessitore A, Scotto di Clemente F, Tedeschi G, Russo A. Erenumab Efficacy on Comorbid Cluster Headache in Patients With Migraine: A Real-World Case Series. Headache. 2020;60(6):1187-95.

112. Baker B SB, Cady R, Latham J, Whitaker T, Smith J. Rational Design of a Monoclonal Antibody (mAb) Inhibiting Calcitonin Gene-Related Peptide (CGRP), ALD403, Intended for the Prevention of Migraine. Neurology (Minneap). 2017;88(16 Suppl):P2.155.

113. Pittock SJ, Lennon VA, McKeon A, Mandrekar J, Weinshenker BG, Lucchinetti CF, et al. Eculizumab in AQP4-IgG-positive relapsing neuromyelitis optica spectrum disorders: an open-label pilot study. Lancet Neurol. 2013;12(6):554-62.