##common.pageHeaderLogo.altText##

Original article

Vol. 155 No. 2 (2025)

Treating Menière’s disease with rimegepant

Cite this as:
Swiss Med Wkly. 2025;155:4147
Published
20.02.2025

Summary

A recent hypothesis states that Menière’s disease is caused by inappropriate expression, i.e. enhanced release of the neurotransmitter calcitonin gene-related peptide. Here, we tested this hypothesis by administering rimegepant, a new calcitonin gene-related peptide antagonist approved for the acute treatment of migraine and for the prevention of episodic migraine, to six patients with both Menière’s disease and migraine. Two patients received the first dose of 75 mg rimegepant to treat an acute attack of Menière’s disease. One of these two plus the remaining four patients were treated with 75 mg rimegepant every other day for secondary prevention. One patient developed an allergic reaction after the first administration and was excluded from further treatment. In the two patients treated during acute Menière’s disease, symptoms were relieved and resolved about 30 min earlier than migraine symptoms. While all five patients had reduced migraine, all completely resolved Menière's symptoms on preventive therapy with rimegepant for up to eight months. These results support the idea that calcitonin gene-related peptide is linked to the pathogenesis of Menière’s disease and suggest that inhibition of calcitonin gene-related peptide signalling may represent a promising therapeutic option for Menière’s disease patients.

References

  1. Shojaku H, Watanabe Y, Fujisaka M, Tsubota M, Kobayashi K, Yasumura S, et al. Epidemiologic characteristics of definite Ménière’s disease in Japan. A long-term survey of Toyama and Niigata prefectures. ORL J Otorhinolaryngol Relat Spec. 2005;67(5):305–9. 10.1159/000089413
  2. Havia M, Kentala E, Pyykkö I. Prevalence of Menière’s disease in general population of Southern Finland. Otolaryngol Head Neck Surg. 2005 Nov;133(5):762–8. doi: https://doi.org/10.1016/j.otohns.2005.06.015
  3. Harris JP, Alexander TH. Current-day prevalence of Ménière’s syndrome. Audiol Neurootol. 2010;15(5):318–22. doi: https://doi.org/10.1159/000286213
  4. Kim SY, Lee CH, Yoo DM, Kwon MJ, Kim JH, Kim JH, et al. Association Between Meniere Disease and Migraine. JAMA Otolaryngol Head Neck Surg. 2022 May;148(5):457–64. doi: https://doi.org/10.1001/jamaoto.2022.0331
  5. Wang Y, Liang J, Fang Y, Yao D, Zhang L, Zhou Y, et al. Burden of Common Neurologic Diseases in Asian Countries, 1990-2019: An Analysis for the Global Burden of Disease Study 2019. Neurology. 2023 May;100(21):e2141–54. doi: https://doi.org/10.1212/WNL.0000000000207218
  6. Ghavami Y, Mahboubi H, Yau AY, Maducdoc M, Djalilian HR. Migraine features in patients with Meniere’s disease. Laryngoscope. 2016 Jan;126(1):163–8. doi: https://doi.org/10.1002/lary.25344
  7. Headache Classification Committee of the International Headache Society (IHS) The International Classification of Headache Disorders. Headache Classification Committee of the International Headache Society (IHS) The International Classification of Headache Disorders, 3rd edition. Cephalalgia. 2018 Jan;38(1):1–211. doi: https://doi.org/10.1177/0333102417738202
  8. Tabet P, Saliba I. Meniere’s Disease and Vestibular Migraine: Updates and Review of the Literature. J Clin Med Res. 2017 Sep;9(9):733–44. doi: https://doi.org/10.14740/jocmr3126w
  9. Ménière P. Mémoires sur des lesions de l'oreille interne donnant lieu á des symptômes de congestion cérébrale apoplectiforme. lu à l'Académie impériale de médecine dans la séance du 8 janvier 1861. Gazette medicale de Paris [Erstveröffentlichung]. 1861;16:597-601. https://www.ncbi.nlm.nih.gov/nlmcatalog/9805412
  10. Phillips JS, Westerberg B. Intratympanic steroids for Ménière’s disease or syndrome. Cochrane Database Syst Rev. 2011 Jul;(7):CD008514. doi: https://doi.org/10.1002/14651858.CD008514.pub2
  11. Webster KE, Lee A, Galbraith K, Harrington-Benton NA, Judd O, Kaski D, et al. Intratympanic corticosteroids for Ménière’s disease. Cochrane Database Syst Rev. 2023 Feb;2(2):CD015245.
  12. Cooper MW, Kaylie DM. Is endolymphatic sac surgery beneficial for Meniere’s Disease? Laryngoscope. 2020 Dec;130(12):2738–9. doi: https://doi.org/10.1002/lary.28647
  13. Schoo DP, Tan GX, Ehrenburg MR, Pross SE, Ward BK, Carey JP. Intratympanic (IT) Therapies for Menière’s Disease: Some Consensus Among the Confusion. Curr Otorhinolaryngol Rep. 2017 Jun;5(2):132–41. doi: https://doi.org/10.1007/s40136-017-0153-5
  14. Hallpike CS, Cairns H. Observations on the Pathology of Ménière’s Syndrome: (Section of Otology) [Section of Otology]. Proc R Soc Med. 1938 Sep;31(11):1317–36. doi: https://doi.org/10.1177/003591573803101112
  15. Kimura RS. Experimental blockage of the endolymphatic duct and sac and its effect on the inner ear of the guinea pig. A study on endolymphatic hydrops. Ann Otol Rhinol Laryngol. 1967 Aug;76(3):664–87. doi: https://doi.org/10.1177/000348946707600311
  16. Gürkov R, Flatz W, Louza J, Strupp M, Krause E. In vivo visualization of endolyphatic hydrops in patients with Meniere’s disease: correlation with audiovestibular function. Eur Arch Otorhinolaryngol. 2011 Dec;268(12):1743–8. doi: https://doi.org/10.1007/s00405-011-1573-3
  17. Huang Y, Zhao P, Han Z, Xie J, Liu Y, Gong S, et al. Evaluation of the relationship between endolymphatic hydrops and hearing loss in Meniere’s disease based on three-dimensional real inversion recovery sequence. Braz J Otorhinolaryngol. 2023;89(5):101314. doi: https://doi.org/10.1016/j.bjorl.2023.101314
  18. Greco A, Gallo A, Fusconi M, Marinelli C, Macri GF, de Vincentiis M. Meniere’s disease might be an autoimmune condition? Autoimmun Rev. 2012 Aug;11(10):731–8. doi: https://doi.org/10.1016/j.autrev.2012.01.004
  19. Kariya S, Cureoglu S, Fukushima H, Nomiya S, Nomiya R, Schachern PA, et al. Vascular findings in the stria vascularis of patients with unilateral or bilateral Ménière’s disease: a histopathologic temporal bone study. Otol Neurotol. 2009 Oct;30(7):1006–12. doi: https://doi.org/10.1097/MAO.0b013e3181b4ec89
  20. Gacek RR. Ménière’s disease is a viral neuropathy. ORL J Otorhinolaryngol Relat Spec. 2009;71(2):78–86. doi: https://doi.org/10.1159/000189783
  21. Derebery MJ. Prevalence of heat shock protein in patients with Meniere’s disease and allergy. Otolaryngol Head Neck Surg. 2002 Jun;126(6):677–82. doi: https://doi.org/10.1067/mhn.2002.125297
  22. Derebery MJ, Rao VS, Siglock TJ, Linthicum FH, Nelson RA. Menière’s disease: an immune complex-mediated illness? Laryngoscope. 1991 Mar;101(3):225–9. doi: https://doi.org/10.1288/00005537-199103000-00001
  23. Cutrer FM, Baloh RW. Migraine-associated dizziness. Headache. 1992 Jun;32(6):300–4. doi: https://doi.org/10.1111/j.1526-4610.1992.hed3206300.x
  24. Hegemann SC. Menière’s disease caused by CGRP - A new hypothesis explaining etiology and pathophysiology. Redirecting Menière’s syndrome to Menière’s disease. J Vestib Res. 2021;31(4):311–4. doi: https://doi.org/10.3233/VES-200716
  25. Herbert MK, Holzer P. [Neurogenic inflammation. II. pathophysiology and clinical implications]. Anasthesiol Intensivmed Notfallmed Schmerzther. 2002 Jul;37(7):386–94. doi: https://doi.org/10.1055/s-2002-32701
  26. Herbert MK, Holzer P. [Neurogenic inflammation. I. Basic mechanisms, physiology and pharmacology]. Anasthesiol Intensivmed Notfallmed Schmerzther. 2002 Jun;37(6):314–25. doi: https://doi.org/10.1055/s-2002-32233
  27. Frank M, Abouzari M, Djalilian HR. Meniere’s disease is a manifestation of migraine. Curr Opin Otolaryngol Head Neck Surg. 2023 Oct;31(5):313–9. doi: https://doi.org/10.1097/MOO.0000000000000908
  28. Gürkov R. J. I [Vestibular function: migraine extends to the inner ear]. Laryngorhinootologie. 2014;93:814–5.
  29. Baron R, Steenerson KK. A Review of Calcitonin Gene-Related Peptide and Its Implications for Vestibular Disorders. Curr Treat Options Neurol. 2024;26(6):203–28. 10.1007/s11940-024-00792-9
  30. Johnson KW, Morin SM, Wroblewski VJ, Johnson MP. Peripheral and central nervous system distribution of the CGRP neutralizing antibody [125I] galcanezumab in male rats. Cephalalgia. 2019 Sep;39(10):1241–8. doi: https://doi.org/10.1177/0333102419844711
  31. Eftekhari S, Salvatore CA, Johansson S, Chen TB, Zeng Z, Edvinsson L. Localization of CGRP, CGRP receptor, PACAP and glutamate in trigeminal ganglion. Relation to the blood-brain barrier. Brain Res. 2015 Mar;1600:93–109. doi: https://doi.org/10.1016/j.brainres.2014.11.031
  32. Yoshida T, Kobayashi M, Sugimoto S, Teranishi M, Naganawa S, Sone M. Evaluation of the blood-perilymph barrier in ears with endolymphatic hydrops. Acta Otolaryngol. 2021 Aug;141(8):736–41. doi: https://doi.org/10.1080/00016489.2021.1957500
  33. Zhang W, Xie J, Liu H, Wang M. Blood-labyrinth barrier breakdown in Meniere’s disease. Eur Arch Otorhinolaryngol. 2024 May;281(5):2327–32. doi: https://doi.org/10.1007/s00405-023-08353-7
  34. Edvinsson L, Ho TW. CGRP receptor antagonism and migraine. Neurotherapeutics. 2010 Apr;7(2):164–75. doi: https://doi.org/10.1016/j.nurt.2010.02.004
  35. Hostetler ED, Joshi AD, Sanabria-Bohórquez S, Fan H, Zeng Z, Purcell M, 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 Nov;347(2):478–86. doi: https://doi.org/10.1124/jpet.113.206458
  36. Wackym PA, Popper P, Micevych PE. Distribution of calcitonin gene-related peptide mRNA and immunoreactivity in the rat central and peripheral vestibular system. Acta Otolaryngol. 1993 Sep;113(5):601–8. doi: https://doi.org/10.3109/00016489309135871
  37. Lopez-Escamez JA, Carey J, Chung WH, Goebel JA, Magnusson M, Mandalà M, et al.; Classification Committee of the Barany Society; Japan Society for Equilibrium Research; European Academy of Otology and Neurotology (EAONO); Equilibrium Committee of the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS); Korean Balance Society. Diagnostic criteria for Menière’s disease. J Vestib Res. 2015;25(1):1–7. doi: https://doi.org/10.3233/VES-150549
  38. Baráth K, Schuknecht B, Naldi AM, Schrepfer T, Bockisch CJ, Hegemann SC. Detection and grading of endolymphatic hydrops in Menière disease using MR imaging. AJNR Am J Neuroradiol. 2014 Jul;35(7):1387–92. doi: https://doi.org/10.3174/ajnr.A3856
  39. Croop R, Goadsby PJ, Stock DA, Conway CM, Forshaw M, Stock EG, et al. Efficacy, safety, and tolerability of rimegepant orally disintegrating tablet for the acute treatment of migraine: a randomised, phase 3, double-blind, placebo-controlled trial. Lancet. 2019 Aug;394(10200):737–45. doi: https://doi.org/10.1016/S0140-6736(19)31606-X
  40. Yu S, Kim BK, Guo A, Kim MH, Zhang M, Wang Z, et al. Safety and efficacy of rimegepant orally disintegrating tablet for the acute treatment of migraine in China and South Korea: a phase 3, double-blind, randomised, placebo-controlled trial. Lancet Neurol. 2023 Jun;22(6):476–84. doi: https://doi.org/10.1016/S1474-4422(23)00126-6
  41. Benjamin T, Gillard D, Abouzari M, Djalilian HR, Sharon JD. Vestibular and auditory manifestations of migraine. Curr Opin Neurol. 2022 Feb;35(1):84–9. doi: https://doi.org/10.1097/WCO.0000000000001024
  42. Moshtaghi O, Sahyouni R, Lin HW, Ghavami Y, Djalilian HR. A Historical Recount: Discovering Menière’s Disease and Its Association With Migraine Headaches. Otol Neurotol. 2016 Sep;37(8):1199–203. doi: https://doi.org/10.1097/MAO.0000000000001122