Evidence map›Paper›PMID 33626922›Full record

ArticleCephalalgia : an international journal of headache2021

Migraine therapeutics differentially modulate the CGRP pathway.

Minoti Bhakta, Trang Vuong, Tetsuya Taura, David S Wilson, Jennifer R Stratton, Kimberly D Mackenzie

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cephalalgia : an international journal of headache, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
57citing papers in PubMed, 2 pooled it
12.8field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

57 citing papers in PubMed, 2 syntheses or guidelines pooled it, 97 citations in OpenAlex.

  1. Pooled it
  2. Exploring the pharmacological action mechanism ofFrontiers in pharmacology · 2022
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors at 1 institution in 1 country.

Minoti BhaktaTeva Biologics, Redwood City, CA, USA.
Trang VuongTeva Biologics, Redwood City, CA, USA.
Tetsuya TauraTeva Biologics, Redwood City, CA, USA.
David S WilsonTeva Biologics, Redwood City, CA, USA.
Jennifer R StrattonTeva Biologics, Redwood City, CA, USA.
Kimberly D MackenzieTeva Biologics, Redwood City, CA, USA.
US Biologic (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe clinical efficacy of migraine therapeutic agents directed towards the calcitonin-gene related peptide (CGRP) pathway has confirmed the key role of this axis in migraine pathogenesis. Three antibodies against CGRP - fremanezumab, galcanezumab and eptinezumab - and one antibody against the CGRP receptor, erenumab, are clinically approved therapeutics for the prevention of migraine. In addition, two small molecule CGRP receptor antagonists, ubrogepant and rimegepant, are approved for acute migraine treatment. Targeting either the CGRP ligand or receptor is efficacious for migraine treatment; however, a comparison of the mechanism of action of these therapeutic agents is lacking in the literature.

methodsTo gain insights into the potential differences between these CGRP pathway therapeutics, we compared the effect of a CGRP ligand antibody (fremanezumab), a CGRP receptor antibody (erenumab) and a CGRP receptor small molecule antagonist (telcagepant) using a combination of binding, functional and imaging assays.

resultsErenumab and telcagepant antagonized CGRP, adrenomedullin and intermedin cAMP signaling at the canonical human CGRP receptor. In contrast, fremanezumab only antagonized CGRP-induced cAMP signaling at the human CGRP receptor. In addition, erenumab, but not fremanezumab, bound and internalized at the canonical human CGRP receptor. Interestingly, erenumab also bound and internalized at the human AMY

conclusionThe therapeutic effect of agents targeting the CGRP ligand versus receptor for migraine prevention (antibodies) or acute treatment (gepants) may involve distinct mechanisms of action. These findings suggest that differing mechanisms could affect efficacy, safety, and/or tolerability in migraine patients.

Indexed as

Antibodies, MonoclonalAntibodies, Monoclonal, HumanizedAzepinesCalcitonin Gene-Related PeptideCalcitonin Gene-Related Peptide Receptor AntagonistsHumansImidazolesIslet Amyloid PolypeptideMigraine DisordersReceptors, Calcitonin Gene-Related PeptideAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAzepinesCalcitonin Gene-Related PeptideCalcitonin Gene-Related Peptide Receptor AntagonistserenumabfremanezumabImidazolesIslet Amyloid PolypeptideReceptors, Calcitonin Gene-Related PeptidetelcagepantAMY1CGRPerenumabfremanezumabgepantmigraine

Identifiers

PMID33626922
PMCPMC8054164
OpenAlexW3129570026

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.