Migraine

Peck, Kelly R.; Johnson, Yelena L; Smitherman, Todd A.

doi:10.1016/b978-0-12-802973-2.00016-1

Cited by 19 publications

(19 citation statements)

References 87 publications

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“…Migraine is probably one of the oldest ailments, known since ancient times, as noted by the Egyptians, and yet even now, it remains an unmet medical need that is often inadequately recognized and undertreated . The second largest cause of disability in the world, migraine is a complex neurological disease is characterized by attacks lasting between 4 hours and 3 days, and is characterized primarily by a moderate‐to‐severe paroxysmal, unilateral headache that is aggravated by movement, and may be accompanied by associated symptoms of photophobia, phonophobia, osmophobia, allodynia, pain on movement, and nausea and vomiting . First described by Hippocrates over 2400 years ago, aura that commonly manifest as scintillations or expanding circle of scotoma may precede migraine headache in ~20‐30% of cases.…”

Section: Introductionmentioning

confidence: 99%

CGRP and the Trigeminal System in Migraine

et al. 2019

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Objective The goal of this narrative review is to provide an overview of migraine pathophysiology, with an emphasis on the role of calcitonin gene‐related peptide (CGRP) within the context of the trigeminovascular system. Background Migraine is a prevalent and disabling neurological disease that is characterized in part by intense, throbbing, and unilateral headaches. Despite recent advances in understanding its pathophysiology, migraine still represents an unmet medical need, as it is often underrecognized and undertreated. Although CGRP has been known to play a pivotal role in migraine for the last 2 decades, this has now received more interest spurred by the early clinical successes of drugs that block CGRP signaling in the trigeminovascular system. Design This narrative review presents an update on the role of CGRP within the trigeminovascular system. PubMed searches were used to find recent (ie, 2016 to November 2018) published articles presenting new study results. Review articles are also included not as primary references but to bring these to the attention of the reader. Original research is referenced in describing the core of the narrative, and review articles are used to support ancillary points. Results The trigeminal ganglion neurons provide the connection between the periphery, stemming from the interface between the primary afferent fibers of the trigeminal ganglion and the meningeal vasculature and the central terminals in the trigeminal nucleus caudalis. The neuropeptide CGRP is abundant in trigeminal ganglion neurons, and is released from the peripheral nerve and central nerve terminals as well as being secreted within the trigeminal ganglion. Release of CGRP from the peripheral terminals initiates a cascade of events that include increased synthesis of nitric oxide and sensitization of the trigeminal nerves. Secreted CGRP in the trigeminal ganglion interacts with adjacent neurons and satellite glial cells to perpetuate peripheral sensitization, and can drive central sensitization of the second‐order neurons. A shift in central sensitization from activity‐dependent to activity‐independent central sensitization may indicate a mechanism driving the progression of episodic migraine to chronic migraine. The pathophysiology of cluster headache is much more obscure than that of migraine, but emerging evidence suggests that it may also involve hypersensitivity of the trigeminovascular system. Ongoing clinical studies with therapies targeted at CGRP will provide additional, valuable insights into the pathophysiology of this disorder. Conclusions CGRP plays an essential role in the pathophysiology of migraine. Treatments that interfere with the functioning of CGRP in the peripheral trigeminal system are effective against migraine. Blocking sensitization of the trigeminal nerve by attenuating CGRP activity in the periphery may be sufficient to block a migraine attack. Addit...

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Section: Introductionmentioning

confidence: 99%

CGRP and the Trigeminal System in Migraine

et al. 2019

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“…The pathophysiology of migraine is complex and incompletely understood; however, recent advances show promise for new pharmacologic and behavioral interventions . Over the last decade, calcitonin gene‐related peptide (CGRP) monoclonal antibodies have been investigated for the prevention of migraine, and blocking the CGRP receptor has shown clinical benefit for the acute treatment of migraine attack .…”

Section: Introductionmentioning

confidence: 99%

Measures of Functioning in Patients With Episodic Migraine: Findings From a Double‐Blind, Randomized, Placebo‐Controlled Phase 2b Trial With Galcanezumab

et al. 2018

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Objective - To evaluate 12-week changes from baseline of 2 disease-specific patient-reported outcome (PRO) measures in adults with migraine treated with galcanezumab, an investigational humanized antibody binding calcitonin gene-related peptide (CGRP), or placebo. Background - Preventing headache-related functional impairment is an important goal of migraine preventive treatment and a measurement target for PROs. Understanding which drugs have the potential to improve patient functioning in addition to preventing migraine headaches is vital to lessening patient burden. Design/Methods - This Phase 2b double-blind, randomized, placebo-controlled study enrolled adults with episodic migraine. Galcanezumab (120 mg subcutaneous injection; n = 60) or placebo (n = 127) was administered every 28 days for 12 weeks. Post hoc secondary analyses were conducted for those who completed 12 weeks of treatment on 2 PROs: The Migraine-Specific Quality of Life Questionnaire (MSQ) v2.1 and the Headache Impact Test™ (HIT-6). Results - Analysis of covariance revealed significant differences in least square mean changes from baseline between galcanezumab and placebo for all MSQ domains including total mean change placebo of 18.63, galcanezumab of 27.36 (95% CI 2.449, 15.008; P-value of .0067); Role Function-Restrictive mean change placebo of 22.40, galcanezumab of 31.92 (95% CI 2.636, 16.518; P-value of .0071); Role Function-Preventive mean change placebo of 13.43, galcanezumab of 19.76 (95% CI 0.476, 12.185; P-value of .0342); and Emotional Function mean change placebo of 16.88, galcanezumab of 26.61 (95% CI 2.789, 16.674; P-value of .0063). At baseline, mean number of migraine headache days (MHDs) did not correlate with MSQ total scores or HIT-6. At 12 weeks post-treatment, MHD correlated with MSQ and HIT-6 scores (all P < .0001). Change in MHD was associated with change in MSQ domains and change in HIT-6 scores (all P < .0001). Conclusions - In comparison with placebo, treatment with galcanezumab was associated with significant functional improvements as reflected by changes in MSQ scores. Change in MHD was associated with improvements in MSQ and reductions in HIT-6 scores, indicating the clinical importance of these changes in relation to PROs that measure function.

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“…Although the worldwide prevalence of migraine and its associated medical and societal costs are well recognized, inadequate treatment is not uncommon 3, 4, 5, 6, 7. Options for preventive therapy are limited by reasons that include lack of efficacy or intolerability to current therapies.…”

Section: Introductionmentioning

confidence: 99%

100% Response Rate to Galcanezumab in Patients With Episodic Migraine: A Post Hoc Analysis of the Results From Phase 3, Randomized, Double‐Blind, Placebo‐Controlled EVOLVE‐1 and EVOLVE‐2 Studies

et al. 2018

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ObjectiveTo characterize adult patients with episodic migraine who achieved 100% response to galcanezumab treatment.BackgroundGalcanezumab is a humanized monoclonal antibody that selectively binds to the calcitonin gene‐related peptide (CGRP) and has demonstrated efficacy in reducing migraine headache days (MHD) in patients with episodic and chronic migraine.MethodsA post hoc analysis of the proportion of patients with 100% response (100% reduction from baseline in monthly MHD) was calculated for each month from pooled data of 2 double‐blind, 6‐month galcanezumab studies in patients with episodic migraine (4 to 14 MHD and ≥2 migraine attacks per month at baseline). The patients were randomized (1:1:2) to monthly subcutaneous galcanezumab, 120 mg (after 240 mg initial loading dose) or 240 mg, or placebo. A generalized linear mixed model with effects for baseline MHD, treatment, month, and treatment‐by‐month interaction was used to estimate the mean monthly response rate.ResultsThe analysis included 1739 patients treated with galcanezumab, 120 mg (n = 436) or 240 mg (n = 428), or placebo (n = 875). The mean monthly 100% response rate on an average month in the 6‐month double‐blind phase was greater for galcanezumab 120 mg (13.5%) and 240 mg (14.3%) groups vs placebo (5.9%) with odds ratios of 2.5 (95% confidence interval [CI] 1.9, 3.2) and 2.6 (95% CI 2.0, 3.4), respectively (P < .001). The rate of 100% monthly response increased at each month over the 6‐month double‐blind phase with higher rates for galcanezumab dose groups (9 to 21%) than placebo (2 to 10%) (P < .02). Evaluation of 100% response by the number of months showed a greater proportion of galcanezumab‐treated patients in either dose group, compared to placebo, were able to achieve a 100% response (P < .001 up to 3 months); however, though greater than placebo, few galcanezumab patients had ≥4 months of 100% response (P < .02). The proportions of patients with 100% response were greatest in the last 3 months of the treatment. Considering the average number days between nonconsecutive MHD across the 6‐month period (not just during the times of 100% response), the duration of migraine headache‐free periods in the galcanezumab groups was 29 days for those with at least 1 month of 100% response and 55 days for those with at least 3 months of 100% response. This gap was approximately 6 to 11 times greater than the mean gap of 5 days observed at baseline.ConclusionsMore than a third of the patients with episodic migraine treated with galcanezumab 120 mg or 240 mg achieved 100% response for at least 1 month. More patients had 100% monthly response in the last 3 months of the 6‐month double‐blind period. For those with 100% response for at least 1 month, the average time between nonconsecutive MHD for the entire treatment period was nearly 1 month and approached 2 months for patients with 3 or more months of 100% response.

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Migraine

Cited by 19 publications

References 87 publications

CGRP and the Trigeminal System in Migraine

CGRP and the Trigeminal System in Migraine

Measures of Functioning in Patients With Episodic Migraine: Findings From a Double‐Blind, Randomized, Placebo‐Controlled Phase 2b Trial With Galcanezumab

100% Response Rate to Galcanezumab in Patients With Episodic Migraine: A Post Hoc Analysis of the Results From Phase 3, Randomized, Double‐Blind, Placebo‐Controlled EVOLVE‐1 and EVOLVE‐2 Studies

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