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

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 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 exceed the cons.

CGRP monoclonal antibody for preventive treatment of chronic migraine: An update of meta‐analysis

“…Calcitonin gene‐related peptide (CGRP) is a promising target to treat migraine, which has a crucial role in migraine pathophysiology. And CGRP antagonisms and CGRP monoclonal antibody (mAb) are the drugs to inhibit the CGRP pathway resulting in the migraine treatment (Deen et al, ; Deneris, Rosati Allen, Hart Hayes, & Latendresse, ; Messlinger, ; Negro, Lionetto, Simmaco, & Martelletti, ; Schuster & Rapoport, ; Yuan, Lauritsen, & Kaiser, ). Some of CGRP antagonisms related clinical trials are discontinued because of the liver injury after repeated administrations (Hong & Liu, ; Hong, Wu, & Liu, ).…”

Recommendations on the Use of Anti‐CGRP Monoclonal Antibodies in Children and Adolescents

“…Another consideration is CGRP expression in the anterior pituitary. The pituitary gland is outside the blood‐brain barrier, and anti‐CGRP mAbs could theoretically affect pituitary function, such as by reducing growth hormone secretion …”

“…In adults, monoclonal antibodies (mAbs) to calcitonin gene‐related peptide (CGRP), or its receptor, have been shown to be efficacious for migraine prevention, and in episodic cluster headache . Although CGRP is expressed in multiple body systems, trials to date have demonstrated minimal adverse events. The most commonly seen adverse events in adult trials included: injection site reactions, upper respiratory symptoms, and constipation.…”

CGRP and Brain Functioning: Cautions for Migraine Treatment

“…Erenumab had only a small effect on angina during treadmill exercise in patients with coronary artery disease (however, see Maassen van den Brink et al). Drug‐drug interactions are very unlikely with mAbs . Nonetheless, identifying subtle effects that may become consequential under particular circumstances or with long‐term use will require more experience with the drugs .…”