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Blocking CGRP in migraine patients – a review of pros and cons

Deen, Marie; Correnti, Edvige; Kamm, Katharina; Kelderman, Tim; Papetti, Laura; Rubio-Beltrán, Eloisa; Vigneri, Simone; Edvinsson, Lars LU and Maassen Van Den Brink, Antoinette (2017) In Journal of Headache and Pain 18. p.1-9
Abstract

Migraine is the most prevalent neurological disorder worldwide and it has immense socioeconomic impact. Currently, preventative treatment options for migraine include drugs developed for diseases other than migraine such as hypertension, depression and epilepsy. During the last decade, however, blocking calcitonin gene-related peptide (CGRP) has emerged as a possible mechanism for prevention of migraine attacks. CGRP has been shown to be released during migraine attacks and it may play a causative role in induction of migraine attacks. Here, we review the pros and cons of blocking CGRP in migraine patients. To date, two different classes of drugs blocking CGRP have been developed: small molecule CGRP receptor antagonists (gepants), and... (More)

Migraine is the most prevalent neurological disorder worldwide and it has immense socioeconomic impact. Currently, preventative treatment options for migraine include drugs developed for diseases other than migraine such as hypertension, depression and epilepsy. During the last decade, however, blocking calcitonin gene-related peptide (CGRP) has emerged as a possible mechanism for prevention of migraine attacks. CGRP has been shown to be released during migraine attacks and it may play a causative role in induction of migraine attacks. Here, we review the pros and cons of blocking CGRP in migraine patients. To date, two different classes of drugs blocking CGRP have been developed: small molecule CGRP receptor antagonists (gepants), and monoclonal antibodies, targeting either CGRP or the CGRP receptor. Several trials have been conducted to test the efficacy and safety of these drugs. In general, a superior efficacy compared to placebo has been shown, especially with regards to the antibodies. In addition, the efficacy is in line with other currently used prophylactic treatments. The drugs have also been well tolerated, except for some of the gepants, which induced a transient increase in transaminases. Thus, blocking CGRP in migraine patients is seemingly both efficient and well tolerated. However, CGRP and its receptor are abundantly present in both the vasculature, and in the peripheral and central nervous system, and are involved in several physiological processes. Therefore, blocking CGRP may pose a risk in subjects with comorbidities such as cardiovascular diseases. In addition, long-term effects are still unknown. Evidence from animal studies suggests that blocking CGRP may induce constipation, affect the homeostatic functions of the pituitary hormones or attenuate wound healing. However, these effects have so far not been reported in human studies. In conclusion, this review suggests that, based on current knowledge, the pros of blocking CGRP in migraine patients exceeds the cons.

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author
organization
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type
Contribution to journal
publication status
published
subject
keywords
Acute treatment, Cgrp, Cgrp receptor, Gepants, Migraine, Prophylactic treatment
in
Journal of Headache and Pain
volume
18
pages
1 - 9
publisher
Springer
external identifiers
  • scopus:85029912523
  • wos:000411746900001
ISSN
1129-2369
DOI
10.1186/s10194-017-0807-1
language
English
LU publication?
yes
id
9df4f064-5247-4791-bac5-23a70f25aa72
date added to LUP
2017-10-06 10:05:09
date last changed
2018-08-12 04:39:47
@article{9df4f064-5247-4791-bac5-23a70f25aa72,
  abstract     = {<p>Migraine is the most prevalent neurological disorder worldwide and it has immense socioeconomic impact. Currently, preventative treatment options for migraine include drugs developed for diseases other than migraine such as hypertension, depression and epilepsy. During the last decade, however, blocking calcitonin gene-related peptide (CGRP) has emerged as a possible mechanism for prevention of migraine attacks. CGRP has been shown to be released during migraine attacks and it may play a causative role in induction of migraine attacks. Here, we review the pros and cons of blocking CGRP in migraine patients. To date, two different classes of drugs blocking CGRP have been developed: small molecule CGRP receptor antagonists (gepants), and monoclonal antibodies, targeting either CGRP or the CGRP receptor. Several trials have been conducted to test the efficacy and safety of these drugs. In general, a superior efficacy compared to placebo has been shown, especially with regards to the antibodies. In addition, the efficacy is in line with other currently used prophylactic treatments. The drugs have also been well tolerated, except for some of the gepants, which induced a transient increase in transaminases. Thus, blocking CGRP in migraine patients is seemingly both efficient and well tolerated. However, CGRP and its receptor are abundantly present in both the vasculature, and in the peripheral and central nervous system, and are involved in several physiological processes. Therefore, blocking CGRP may pose a risk in subjects with comorbidities such as cardiovascular diseases. In addition, long-term effects are still unknown. Evidence from animal studies suggests that blocking CGRP may induce constipation, affect the homeostatic functions of the pituitary hormones or attenuate wound healing. However, these effects have so far not been reported in human studies. In conclusion, this review suggests that, based on current knowledge, the pros of blocking CGRP in migraine patients exceeds the cons.</p>},
  articleno    = {96},
  author       = {Deen, Marie and Correnti, Edvige and Kamm, Katharina and Kelderman, Tim and Papetti, Laura and Rubio-Beltrán, Eloisa and Vigneri, Simone and Edvinsson, Lars and Maassen Van Den Brink, Antoinette},
  issn         = {1129-2369},
  keyword      = {Acute treatment,Cgrp,Cgrp receptor,Gepants,Migraine,Prophylactic treatment},
  language     = {eng},
  month        = {12},
  pages        = {1--9},
  publisher    = {Springer},
  series       = {Journal of Headache and Pain},
  title        = {Blocking CGRP in migraine patients – a review of pros and cons},
  url          = {http://dx.doi.org/10.1186/s10194-017-0807-1},
  volume       = {18},
  year         = {2017},
}