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Evaluation of the risk of hypertension in patients treated with anti-CGRP monoclonal antibodies in a real-life study

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Abstract

Objective

To explore the rate of hypertension incoming in patients treated with monoclonal antibodies against the calcitonin gene-related peptide.

Background

The monoclonal antibodies blocking the calcitonin gene-related peptide are unquestionable effective in the prevention of migraine. Despite this, the development of hypertension has been detected in some patients.

Methods

This was a retrospective study conducted at the University Hospital of Modena. Patients were visited quarterly up to 1 year.

Results

Globally, no significant increase in the blood pressure was detected. The 5.7% of the patients developed a significant increase in their blood pressure. In particular, patients with a pre-existing hypertension were more likely to have a significant increase in the blood pressure.

Conclusion

The risk of develo** hypertension during a treatment with anti-calcitonin gene-related peptide monoclonal antibodies seems low. Anyway, patients with a pre-existing hypertension should be cautiously monitored because they are more likely to develop hypertension.

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Data availability

The dataset generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

References

  1. Headache Classification Committee of the International Headache Society (IHS) (2018) The International Classification of Headache Disorders, 3rd edition. Cephalalgia 38:1–211. https://doi.org/10.1177/0333102417738202

    Article  Google Scholar 

  2. Sacco S, Amin FM, Ashina M, Bendtsen L, Deligianni CI, Gil-Gouveia R, Katsarava Z, MaassenVanDenBrink A, Martelletti P, Mitsikostas DD, Ornello R, Reuter U, Sanchez-Del-Rio M, Sinclair AJ, Terwindt G, Uluduz D, Versijpt J, Lampl C (2022) European Headache Federation guideline on the use of monoclonal antibodies targeting the calcitonin gene related peptide pathway for migraine prevention - 2022 update. J Headache Pain 23:67. https://doi.org/10.1186/s10194-022-01431-x

    Article  PubMed  PubMed Central  Google Scholar 

  3. Do TP, Guo S, Ashina M (2019) Therapeutic novelties in migraine: new drugs, new hope? J Headache Pain 20:37. https://doi.org/10.1186/s10194-019-0974-3

    Article  PubMed  PubMed Central  Google Scholar 

  4. Hepp Z, Dodick DW, Varon SF, Gillard P, Hansen RN, Devine EB (2015) Adherence to oral migraine-preventive medications among patients with chronic migraine. Cephalalgia 35:478–488. https://doi.org/10.1177/0333102414547138

    Article  PubMed  Google Scholar 

  5. MaassenVanDenBrink A, Meijer J, Villalón CM, Ferrari MD (2016) Wi** out CGRP: potential cardiovascular risks. Trends Pharmacol Sci 37:779–788. https://doi.org/10.1016/j.tips.2016.06.002

    Article  CAS  PubMed  Google Scholar 

  6. de Hoon JN, Pickkers P, Smits P, Struijker-Boudier HA, Van Bortel LM (2003) Calcitonin gene-related peptide: exploring its vasodilating mechanism of action in humans. Clin Pharmacol Ther 73:312–321. https://doi.org/10.1016/s0009-9236(03)00007-9

    Article  PubMed  Google Scholar 

  7. Argunhan F, Brain SD (2022) The vascular-dependent and -independent actions of calcitonin gene-related peptide in cardiovascular disease. Front Physiol 13:833645. https://doi.org/10.3389/fphys.2022.833645

    Article  PubMed  PubMed Central  Google Scholar 

  8. Mathew PG, Klein BC (2019) Getting to the heart of the matter: migraine, triptans, DHE, ditans, CGRP antibodies, first/second-generation gepants, and cardiovascular risk. Headache 59:1421–1426. https://doi.org/10.1111/head.136012

    Article  PubMed  Google Scholar 

  9. Dodick DW, Tepper SJ, Ailani J, Pannacciulli N, Navetta MS, Loop B, Zhang F, Khodavirdi AC, Mann A, Abdrabboh A, Kalim J (2021) Risk of hypertension in erenumab-treated patients with migraine: analyses of clinical trial and postmarketing data. Headache 61:1411–1420. https://doi.org/10.1111/head.14208

    Article  PubMed  PubMed Central  Google Scholar 

  10. Booth CM, Tannock IF (2014) Randomised controlled trials and population-based observational research: partners in the evolution of medical evidence. Br J Cancer 110:551–555. https://doi.org/10.1038/bjc.2013.725

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Bigal ME, Kurth T, Hu H, Santanello N, Lipton RB (2009) Migraine and cardiovascular disease: possible mechanisms of interaction. Neurology 72:1864–1871. https://doi.org/10.1212/WNL.0b013e3181a71220

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Stergiou GS, Mukkamala R, Avolio A, Kyriakoulis KG, Mieke S, Murray A, Parati G, Schutte AE, Sharman JE, Asmar R, RJ MM, Asayama K, De La Sierra A, Head G, Kario K, Kollias A, Myers M, Niiranen T, Ohkubo T et al (2022) Cuffless blood pressure measuring devices: review and statement by the European Society of Hypertension Working Group on Blood Pressure Monitoring and Cardiovascular Variability. J Hypertens 40:1449–1460. https://doi.org/10.1097/HJH.0000000000003224

    Article  CAS  PubMed  Google Scholar 

  13. de Vries LS, van der Arend BWH, Maassen VanDenBrink A, Terwindt GM (2022) Blood pressure in patients with migraine treated with monoclonal anti-CGRP (receptor) antibodies: a prospective follow-up study. Neurology 99:e1897–e1904. https://doi.org/10.1212/WNL.0000000000201008

    Article  CAS  Google Scholar 

  14. Elgendy IY, Nadeau SE, Bairey Merz CN, Pepine CJ (2019) American College of Cardiology Cardiovascular Disease in Women Committee Migraine headache: an under-appreciated risk factor for cardiovascular disease in women. J Am Heart Assoc 8:e014546. https://doi.org/10.1161/JAHA.119.014546

  15. Kurth T, Rist PM, Ridker PM, Kotler G, Bubes V, Buring JE (2020) Association of migraine with aura and other risk factors with incident cardiovascular disease in women. JAMA 323:2281–2289. https://doi.org/10.1001/jama.2020.7172

    Article  PubMed  PubMed Central  Google Scholar 

  16. Wang K, Mao Y, Lu M, Ding Y, Li Z, Li Y, Liu X, Sun Y, Hong J, Xu D, Wu T (2022) Association between migraine and cardiovascular disease: a cross-sectional study. Front Cardiovasc Med 9:1044465. https://doi.org/10.3389/fcvm.2022.1044465

    Article  PubMed  PubMed Central  Google Scholar 

  17. Sohn I, Sheykhzade M, Edvinsson L, Sams A (2020) The effects of CGRP in vascular tissue - classical vasodilation, shadowed effects and systemic dilemmas. Eur J Pharmacol 881:173205. https://doi.org/10.1016/j.ejphar.2020.173205

    Article  CAS  PubMed  Google Scholar 

  18. Brain SD, Tippins JR, Morris HR, MacIntyre I, Williams TJ (1986) Potent vasodilator activity of calcitonin gene-related peptide in human skin. J Invest Dermatol 87:533–536. https://doi.org/10.1111/1523-1747.ep12455620

    Article  CAS  PubMed  Google Scholar 

  19. Uddman R, Edvinsson L, Jansen I, Stiernholm P, Jensen K, Olesen J, Sundler F (1986) Peptide-containing nerve fibres in human extracranial tissue: a morphological basis for neuropeptide involvement in extracranial pain? Pain 27:391–399. https://doi.org/10.1016/0304-3959(86)90162-4

    Article  PubMed  Google Scholar 

  20. Ye F, Deng PY, Li D, Luo D, Li NS, Deng S, Deng HW, Li YJ (2007) Involvement of endothelial cell-derived CGRP in heat stress-induced protection of endothelial function. Vascul Pharmacol 46:238–246. https://doi.org/10.1016/j.vph.2006.10.008

    Article  CAS  PubMed  Google Scholar 

  21. Krämer HH, Schmidt K, Leis S, Schmelz M, Sommer C, Birklein F (2006) Angiotensin converting enzyme has an inhibitory role in CGRP metabolism in human skin. Peptides 27:917–920. https://doi.org/10.1016/j.peptides.2005.08.007

    Article  CAS  PubMed  Google Scholar 

  22. Edvinsson L, Chan KY, Eftekhari S, Nilsson E, de Vries R, Säveland H, Dirven CM, Danser AH, MaassenVanDenBrink A (2010) Effect of the calcitonin gene-related peptide (CGRP) receptor antagonist telcagepant in human cranial arteries. Cephalalgia 30:1233–1240. https://doi.org/10.1177/0333102410362122

    Article  PubMed  Google Scholar 

  23. Jansen-Olesen I, Jørgensen L, Engel U, Edvinsson L (2003) In-depth characterization of CGRP receptors in human intracranial arteries. Eur J Pharmacol 481:207–216. https://doi.org/10.1016/j.ejphar.2003.09.021

    Article  CAS  PubMed  Google Scholar 

  24. Chan KY, Edvinsson L, Eftekhari S, Kimblad PO, Kane SA, Lynch J, Hargreaves RJ, de Vries R, Garrelds IM, van den Bogaerdt AJ, Danser AH, Maassenvandenbrink A (2010) Characterization of the calcitonin gene-related peptide receptor antagonist telcagepant (MK-0974) in human isolated coronary arteries. J Pharmacol Exp Ther 334:746–752. https://doi.org/10.1124/jpet.110.165993

    Article  CAS  PubMed  Google Scholar 

  25. Eftekhari S, Warfvinge K, Blixt FW, Edvinsson L (2013) Differentiation of nerve fibers storing CGRP and CGRP receptors in the peripheral trigeminovascular system. J Pain 14:1289–1303. https://doi.org/10.1016/j.jpain.2013.03.010

    Article  CAS  PubMed  Google Scholar 

  26. Wellman GC, Quayle JM, Standen NB (1998) ATP-sensitive K+ channel activation by calcitonin gene-related peptide and protein kinase A in pig coronary arterial smooth muscle. J Physiol 507:117–129. https://doi.org/10.1111/j.1469-7793.1998.117bu.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Yoshimoto R, Mitsui-Saito M, Ozaki H, Karaki H (1998) Effects of adrenomedullin and calcitonin gene-related peptide on contractions of the rat aorta and porcine coronary artery. Br J Pharmacol 123:1645–1654. https://doi.org/10.1038/sj.bjp.0701805

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Brain SD, Grant AD (2004) Vascular actions of calcitonin gene-related peptide and adrenomedullin. Physiol Rev 84:903–934. https://doi.org/10.1152/physrev.00037.2003

    Article  CAS  PubMed  Google Scholar 

  29. Juhl L, Edvinsson L, Olesen J, Jansen-Olesen I (2007) Effect of two novel CGRP-binding compounds in a closed cranial window rat model. Eur J Pharmacol 567:117–124. https://doi.org/10.1016/j.ejphar.2007.04.004

    Article  CAS  PubMed  Google Scholar 

  30. Schain AJ, Melo-Carrillo A, Stratton J, Strassman AM, Burstein R (2019) CSD-induced arterial dilatation and plasma protein extravasation are unaffected by fremanezumab: implications for CGRP's role in migraine with aura. J Neurosci 39:6001–6011. https://doi.org/10.1523/JNEUROSCI.0232-19.2019

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Edvinsson L, Nilsson E, Jansen-Olesen I (2007) Inhibitory effect of BIBN4096BS, CGRP(8-37), a CGRP antibody and an RNA-Spiegelmer on CGRP induced vasodilatation in the perfused and non-perfused rat middle cerebral artery. Br J Pharmacol 150:633–640. https://doi.org/10.1038/sj.bjp.0707134

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Edvinsson L, Ekman R, Thulin T (1989) Circulating perivascular dilatory neuropeptides in hypertension. J Hypertens Suppl 7:S194–S195. https://doi.org/10.1097/00004872-198900076-00093

    Article  CAS  PubMed  Google Scholar 

  33. Schifter S, Krusell LR, Sehested J (1991) Normal serum levels of calcitonin gene-related peptide (CGRP) in mild to moderate essential hypertension. Am J Hypertens 4:565–569. https://doi.org/10.1093/ajh/4.7.565

    Article  CAS  PubMed  Google Scholar 

  34. Masuda A, Shimamoto K, Mori Y, Nakagawa M, Ura N, Iimura O (1992) Plasma calcitonin gene-related peptide levels in patients with various hypertensive diseases. J Hypertens 10:1499–1504. https://doi.org/10.1097/00004872-199210120-00010

    Article  CAS  PubMed  Google Scholar 

  35. Portaluppi F, Trasforini G, Margutti A, Vergnani L, Ambrosio MR, Rossi R, Bagni B, Pansini R, Degli Uberti EC (1992) Circadian rhythm of calcitonin gene-related peptide in uncomplicated essential hypertension. J Hypertens 10:1227–1234. https://doi.org/10.1097/00004872-199210000-00017

    Article  CAS  PubMed  Google Scholar 

  36. Edvinsson L, Erlinge D, Ekman R (1992) Thulin T (1992) Sensory nerve terminal activity in severe hypertension as reflected by circulating calcitonin gene-related peptide (CGRP) and substance P. Blood Press 1:223–229. https://doi.org/10.3109/08037059209077667

    Article  CAS  PubMed  Google Scholar 

  37. Lind H, Brudin L, Lindholm L, Edvinsson L (1996) Different levels of sensory neuropeptides (calcitonin gene-related peptide and substance P) during and after exercise in man. Clin Physiol 16:73–82. https://doi.org/10.1111/j.1475-097x.1996.tb00557.x

    Article  CAS  PubMed  Google Scholar 

  38. Li J, Wang DH (2005) Development of angiotensin II-induced hypertension: role of CGRP and its receptor. J Hypertens 23:11311–11318. https://doi.org/10.1097/00004872-200501000-00020

    Article  Google Scholar 

  39. Strecker T, Dux M, Messlinger K (2002) Increase in meningeal blood flow by nitric oxide--interaction with calcitonin gene-related peptide receptor and prostaglandin synthesis inhibition. Cephalalgia 22:233–241. https://doi.org/10.1046/j.1468-2982.2002.00356.x

    Article  CAS  PubMed  Google Scholar 

  40. Etefagh HH, Shahmiri SS, Melali H, Sayadi M, Ansari H, Shahzamani A, Deyhimi MS (2022) Bariatric surgery in migraine patients: CGRP level and weight loss. Obes Surg 32(11):3635–3640. https://doi.org/10.1007/s11695-022-06218-2

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Digital and Predictive Medicine, Pharmacology and Clinical Metabolic Toxicology-Headache Center and Drug Abuse-Laboratory of Clinical Pharmacology and Pharmacogenomics; Department of Specialist Medicines, AOU Policlinico di Modena, Modena, Italy

    Simona Guerzoni, Flavia Lo Castro, Daria Brovia & Luca Pani

  2. Pharmacology Unit; Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy

    Carlo Baraldi & Luca Pani

  3. Department of Psychiatry and Behavioral Sciences, University of Miami, Coral Gables, USA

    Luca Pani

  4. VeraSci, Durham, USA

    Luca Pani

Authors
  1. Simona Guerzoni
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  2. Flavia Lo Castro
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  3. Daria Brovia
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  4. Carlo Baraldi
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  5. Luca Pani
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Contributions

All authors contributed to the study conception, design, material preparation, data collection, and analysis. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Flavia Lo Castro.

Ethics declarations

Ethics approval

Data were desumed from patients enrolled in two studies approved by the AVEN Ethics Committee (protocol numbers: 625/2020/OSS/AOUMO and 50/2020/OSS/AOUMO). The study was conducted according to the latest version of the Declaration of Helsinki.

Informed consent

All patients signed a free-informed consent for study participation and data publication.

Conflict of interest

SG received fees and honoraria from Teva, Eli Lilly, Allergan/Abbvie, Novartis, Pfizer, and Lundbeck; CB received fees and honoraria from Teva, Eli Lilly, Allergan/Abbvie, Novartis, and Lundbeck. LP has been a scientific consultant for AbbVie, USA; Acadia, USA; BCG, Switzerland; Boehringer Ingelheim International GmbH, Germany; Compass Pathways, UK; Immunogen, USA; Inpeco SA, Switzerland; Johnson & Johnson USA; Novartis-Gene Therapies, Switzerland; Sanofi-Aventis-Genzyme, France and USA; Nurosene-NetraMark, Canada; Pfizer Global, USA; PharmaMar, Spain; Relmada Therapeutics, USA; Takeda, USA; Vifor, Switzerland; and WCG-VeraSci/Clinical Endpoint Solutions, USA, and he owns shares of Relmada, USA, and NetraMark, Canada. FLC and BD have no conflict of interest to disclose.

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Guerzoni, S., Castro, F.L., Brovia, D. et al. Evaluation of the risk of hypertension in patients treated with anti-CGRP monoclonal antibodies in a real-life study. Neurol Sci 45, 1661–1668 (2024). https://doi.org/10.1007/s10072-023-07167-z

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  • DOI: https://doi.org/10.1007/s10072-023-07167-z

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