scholarly journals Current status of calcitonin gene-related peptide-based therapies in migraine: a scoping review

2022 ◽  
Author(s):  
Marya Ahsan ◽  
Ayaz Khurram Mallick
Keyword(s):  
Clinical Trials ◽  
Monoclonal Antibodies ◽  
Small Molecule ◽  
Significant Proportion ◽  
Calcitonin Gene Related Peptide ◽  
Phase Iii ◽  
Current Status ◽  
Cgrp Receptor ◽  
Related Peptide ◽  
Calcitonin Gene

A significant proportion of patients exhibit sub-optimal response to the standard treatment of acute migraine such as triptans and NSAIDs. Even the conventional preventive therapies (e.g. beta-blockers) indicated for patients with frequent migraine attacks have varying responses. Moreover, evidence from animal studies elucidated the role of calcitonin gene-related peptide (CGRP) in the pathophysiology of migraine. Currently two classes are drug, the small molecule CGRP receptor antagonist or the ‘gepants’ (Ubrogepant, Rimegepant, Atogepant, Zavegepant) and CGRP monoclonal antibodies (Erenumab, Galcanezumab, Fremanezumab, Eptinezumab) have been found efficacious and safe in various clinical trials for the treatment and prevention of migraine. While the small molecule CGRP receptor antagonists are given orally, the monoclonal antibodies are injectable drugs. Ubrogepant and Rimegepant are the second-generation gepants approved for treatment of migraine. Zavegepant is a third generation gepant which has proven efficacy for acute treatment of migraine in a phase III trial. Atogepant has been approved for prevention of migraine. Rimegepant has also proven to be efficacious for preventing migraine attacks but has not yet been approved for this indication. Erenumab is the only monoclonal antibody which neutralizes the CGRP receptor. The latter three monoclonal antibodies target the CGRP peptide. The monoclonal antibodies have been approved for the prevention of migraine as a subcutaneously or intravenous infusion (Eptinezumab) given once a month or quarterly. Both the classes of drugs were well-tolerated in the clinical trials. Nausea was the most common adverse effect with gepants while injection-site pain was commonly reported with the antibodies.

Fremanezumab autoinjector pen for the prevention of migraine

2021 ◽  
Author(s):  
Mark W Weatherall
Keyword(s):  
Monoclonal Antibody ◽  
Clinical Trials ◽  
Calcitonin Gene Related Peptide ◽  
Phase Iii ◽  
Tolerability Profile ◽  
Related Peptide ◽  
Phase Iii Clinical Trials ◽  
Humanized Monoclonal Antibody ◽  
Calcitonin Gene ◽  
Favorable Tolerability Profile

Ajovy (fremanezumab, Teva Pharmaceuticals, Israel) is a fully humanized monoclonal antibody that selectively binds both isoforms of the calcitonin gene-related peptide. Calcitonin gene-related peptide is a 37-amino acid neuropeptide involved in central and peripheral pathophysiological events in migraine. It is indicated for prophylaxis of migraine in adults who have at least four migraine days per month, and can be administered as a subcutaneous injection using an autoinjector device, with two dosing options: 225 mg once a month or 675 mg quarterly. In this article, I present data from Phase III clinical trials of fremanezumab in episodic and chronic migraine, in which fremanezumab demonstrated efficacy and had a favorable tolerability profile, with no serious treatment-related adverse events.

scholarly journals Efficacy and Safety of Monoclonal Antibody Against Calcitonin Gene-Related Peptide or Its Receptor for Migraine: A Systematic Review and Network Meta-analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Xing Wang ◽  
Yuqi Chen ◽  
Jinlei Song ◽  
Chao You
Keyword(s):  
Monoclonal Antibody ◽  
Clinical Trials ◽  
Monoclonal Antibodies ◽  
Adverse Events ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Calcitonin Gene Related Peptide ◽  
Adult Patients ◽  
Related Peptide ◽  
Calcitonin Gene

Background: The optimal monoclonal antibody against calcitonin gene-related peptide (CGRP) for adult patients with migraine has yet to be determined. Therefore, we aimed to compare the effectiveness of different monoclonal antibodies against CGRP or its receptor for adult patients with migraine through a network meta-analysis of randomized controlled trials.Methods: We systematically searched the MEDILNE, Embase, ClinicalTrials.gov, and Cochrane Library databases for relevant publications from inception until October 30, 2020. Only randomized clinical trials of adults with migraine that assessed any calcitonin gene-related peptide monoclonal antibody and reported clinical outcomes were included. The primary outcomes were changes in monthly migraine days and treatment-emergent adverse eventsResults: We initially retrieved 2,070 publications, and ultimately, 18 randomized clinical trials totaling 8,926 patients were included. In terms of efficacy, eptinezumab (MD −1.43, 95% CrI −2.59 to −0.36), erenumab (MD −1.61, 95% CrI −2.40 to −0.84), fremanezumab (MD −2.19, 95% CrI −3.15 to −1.25), and galcanezumab (MD −2.10, 95% CrI −2.76 to −1.45) significantly reduced MMDs compared with placebo. In terms of safety, only galcanezumab increased the incidences of TEAEs (RR 1.11, 95% CrI 1.01–1.22) and serious adverse events (RR 2.95, 95% CrI 1.41–6.87) compared with placebo.Conclusion: Most drugs performed similarly and were superior to placebo in most of our analyses. Further head-to-head research on different types of CGRP monoclonal antibodies is necessary to validate the present findings.

Calcitonin gene-related peptide receptors in rat trigeminal ganglion do not control spinal trigeminal activity

2012 ◽  
Vol 108 (2) ◽  
pp. 431-440 ◽  
Author(s):  
Oana Covasala ◽  
Sören L. Stirn ◽  
Stephanie Albrecht ◽  
Roberto De Col ◽  
Karl Messlinger
Keyword(s):  
Trigeminal Ganglion ◽  
Dura Mater ◽  
Calcitonin Gene Related Peptide ◽  
Afferent Input ◽  
Nitric Oxide Donor ◽  
Cgrp Receptor ◽  
Related Peptide ◽  
Trigeminal Neurons ◽  
Calcitonin Gene ◽  
Evoked Activity

Calcitonin gene-related peptide (CGRP) is regarded as a key mediator in the generation of primary headaches. CGRP receptor antagonists reduce migraine pain in clinical trials and spinal trigeminal activity in animal experiments. The site of CGRP receptor inhibition causing these effects is debated. Activation and inhibition of CGRP receptors in the trigeminal ganglion may influence the activity of trigeminal afferents and hence of spinal trigeminal neurons. In anesthetized rats extracellular activity was recorded from neurons with meningeal afferent input in the spinal trigeminal nucleus caudalis. Mechanical stimuli were applied at regular intervals to receptive fields located in the exposed cranial dura mater. α-CGRP (10−5 M), the CGRP receptor antagonist olcegepant (10−3 M), or vehicle was injected through the infraorbital canal into the trigeminal ganglion. The injection of volumes caused transient discharges, but vehicle, CGRP, or olcegepant injection was not followed by significant changes in ongoing or mechanically evoked activity. In animals pretreated intravenously with the nitric oxide donor glyceryl trinitrate (GTN, 250 μg/kg) the mechanically evoked activity decreased after injection of CGRP and increased after injection of olcegepant. In conclusion, the activity of spinal trigeminal neurons with meningeal afferent input is normally not controlled by CGRP receptor activation or inhibition in the trigeminal ganglion. CGRP receptors in the trigeminal ganglion may influence neuronal activity evoked by mechanical stimulation of meningeal afferents only after pretreatment with GTN. Since it has previously been shown that olcegepant applied to the cranial dura mater is ineffective, trigeminal activity driven by meningeal afferent input is more likely to be controlled by CGRP receptors located centrally to the trigeminal ganglion.

Early Experiences in Switching between Monoclonal Antibodies in Patients with Nonresponsive Migraine in Spain: A Case Series

2021 ◽  
pp. 1-4
Author(s):  
Ignacio Patier Ruiz ◽  
Javier Sánchez-Rubio Ferrández ◽  
Alba Cárcamo Fonfría ◽  
Teresa Molina García
Keyword(s):  
Clinical Trials ◽  
Monoclonal Antibodies ◽  
Therapeutic Targets ◽  
Case Series ◽  
Similar Efficacy ◽  
Migraine Prophylaxis ◽  
Therapeutic Failure ◽  
Related Peptide ◽  
Early Experiences ◽  
Calcitonin Gene

Monoclonal antibodies targeting the calcitonin gene-related peptide have been introduced into the therapeutic arsenal of migraine prophylaxis. Clinical trials report similar efficacy between them, and there is no evidence of switching to another one after failure. We aim to describe our experience in switching from erenumab to galcanezumab after therapeutic failure. We retrospectively reviewed 30 migraine patients who received monoclonal antibodies, with 15 of them switched after failure to achieve reduction in migraine days per month ≥30%. A ≥30% reduction in migraine days per month compared to baseline was observed in 8/15 (4/15 ≥ 50%) patients after switch. Some nonresponsive patients may benefit from switching between monoclonal antibodies with different therapeutic targets.

Calcitonin-Gene-Related Peptide (CGRP) Monoclonal Antibodies in Migraine Prevention; Literature Review

2021 ◽  
Vol 10 (1) ◽  
pp. 48-51
Author(s):  
Haneen Ahmed Khouja ◽  
Rawan Awadh Alshehri ◽  
Hussain Mirza Alhalal ◽  
Hassan Dhafer Alabisi ◽  
Salhah Mohammad Alajmi ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Literature Review ◽  
Calcitonin Gene Related Peptide ◽  
Migraine Prevention ◽  
Related Peptide ◽  
Calcitonin Gene
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