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Table of Contents
DRUG CORNER
Year : 2019  |  Volume : 7  |  Issue : 4  |  Page : 142-144

Chronic migraine: Erenumab, new kid on the block


Department of Pharmacology, GMCH, Amritsar, Punjab, India

Date of Submission10-Jul-2019
Date of Acceptance06-Aug-2019
Date of Web Publication18-Oct-2019

Correspondence Address:
Dr. Divya Goel
1154-A, Sector 32, Chandigarh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/AJIM.AJIM_27_19

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  Abstract 

Migraine is a primary headache disorder and causes substantial pain and disability. Migraine sufferers could suffer from episodic migraine or chronic migraine. While both of these adversely affect the quality of life, the management of chronic migraine patients poses many challenges, as it mainly relies on preventive treatment. Till now, we have very limited options for preventive management of chronic migraine; recently, new drug erenumab has been approved by the Food and Drug Administration. It has shown very promising results in the management of chronic migraine as it acts by novel mechanism as calcitonin gene-related peptide receptor blocker.

Keywords: Calcitonin gene-related peptide, chronic migraine, erenumab, migraine


How to cite this article:
Goel D. Chronic migraine: Erenumab, new kid on the block. APIK J Int Med 2019;7:142-4

How to cite this URL:
Goel D. Chronic migraine: Erenumab, new kid on the block. APIK J Int Med [serial online] 2019 [cited 2019 Dec 5];7:142-4. Available from: http://www.ajim.in/text.asp?2019/7/4/142/269561




  Introduction Top


Millions of people suffer from migraine all over the world, with estimated prevalence of 14.7%,[1] and it is the second most common reported cause of headache.[2] Usually, migraine is episodic headache associated with other symptoms such as sensitivity to light, sound, or movement; nausea; and vomiting,[2] but around 1%–2% of the world population is found to be suffering from chronic migraine.[3] Most of the times, episodic migraine sufferers progress to chronic migraine with annual progression rate of 3% rather than primary chronic migraine, and out of this, about 26% patients suffering from chronic migraine remit within 2 years of onset.[4] As per International Classification of Headache Disorders (ICHD-3 beta), chronic migraine is defined as headaches on at least 15 days/month for ≥3 months, with at least 8 headache days/month fulfilling the criteria for migraine headaches.[5]

Pathophysiology of transformation from episodic migraine to chronic migraine is not well understood. Migraine is cyclic headache with increased susceptibility to certain triggers just before an attack.[6],[7] In-between the attacks, sensitivity to various stimuli is normal; these oscillatory changes in sensitivity might originate from the limbic system because of change in pain threshold level.[8] Many factors lower down this pain threshold, that is, stressful life events, obesity, and depression, and these factors increase the chances of migraine attacks.[8] With the increase in frequency of migraine attacks, pain threshold level remains above the basal level. High attack frequency is one of the risk factors for chronification of migraine; so, chronic migraine can be due to pain threshold problem.[4],[9] Decrease in pain threshold leads to increased nociceptive processing that leads to increased activity of descending pain modulatory pathway and its dysfunction.[10],[11] In addition, calcitonin gene-related peptide (CGRP) is found to play an important role in the pathophysiology of migraine; many studies have shown that CGRP peptide neurotransmitter is released into the circulation during migraine attack,[12] and level of CGRP remains elevated in patients suffering from chronic migraine.[13] CGRP is the most abundant neuropeptide in the trigeminal nerve, and the trigeminovascular pathway has been implicated in the pathogenesis of migraine.[14] Trigeminovascular pathway comprised the trigeminal nerve, the cranial vasculature it innervates, and the spinal trigeminal nuclei in the brainstem. CGRP released from these neurons is proposed to act locally in the vascular smooth muscle. CGRP binds to CGRP receptors (CGPR-R), and activated CGRP-R results in dilation of blood vessels.[15] In addition, CGRP leads to nitric oxide and pro-inflammatory cytokine release from glial cells and causes neuronal sensitization and inflammation.[16] Intravenous infusion of CGRP has been shown to produce migraine-like attacks. All these findings implicated CGRP in the pathophysiology of migraine.


  Current Management of Chronic Migraine and Its Pitfall Top


Unlike episodic migraine attack, analgesics are ineffective in managing chronic migraine attack after its onset as they themselves might lead to chronification of migraine apart from other drugs. This condition is known as medication overuse headache (MOH). As per ICHD-3 beta' usage of ergotamines, triptans, combination analgesics, for at least 10 days/month for 3 months, and using simple analgesics (e.g., nonsteroidal anti-inflammatory drugs and paracetamol) for at least 15 days/month for 3 months is associated with MOH.[5] The treatment of chronic migraine should focus on prophylactic therapy, while avoiding migraine triggers and minimizing the use of acute migraine medications.[17] At present, oral prophylactic medication available are topiramate, β-blockers, and amitriptyline, either these are not fully efficacious or are poorly tolerated which lead to less compliance.[18] All of these drugs have modest efficacy as these are primarily been used in other clinical conditions and are not specific for migraine patients. Apart from these, one preventive injectable drug onabotulinum toxin A is approved by the Food and Drug Administration (FDA) for preventive treatment of chronic migraine.[19] Recently, evidence have suggested the involvement of CGRP in pathogenesis of migraine.[10] Recently, erenumab, fremanezumab, and galcanezumab inhibitor of CGRP activity are approveed by the FDA for preventive treatment of migraine.[20]


  Erenumab Top


Thus, a large unmet therapeutic need remains to be fulfilled. Recently, in May 2018, FDA approved first of its kind, fully human monoclonal antibody erenumab for the prevention of migraine in adult patients.[21] Erenumab binds in a competitive and reversible manner to the CGPR-R with greater selectivity than to other human calcitonin family receptors.[22] CGRP is a pro-inflammatory, vasodilating neuropeptide implicated in the pathophysiology of migraine;[23] erenumab blocks these activities of CGRP and helps in the prevention of migraine attack.[24]

The efficacy and safety of erenumab for the preventive treatment of migraine were evaluated in three clinical trials. Two trials were conducted in patients suffering from episodic migraine and one trial in patients suffering from chronic migraine.[21] In the third study, which was a randomized, double-blind, 12-week, placebo-controlled study, a total of 667 patients of chronic migraine were evaluated for the efficacy and safety of erenumab. Patients received two subcutaneous 1 mL injections: either two placebo syringes, one erenumab S.C 70 mg syringe, and one placebo syringe (70 mg group) or two erenumab S.C 70 mg syringes (140 mg group) on day 1, week 4, and week 8.[24]


  Efficacy of Erenumab in Chronic Migraine Top


The primary outcome was the mean change in monthly migraine days in the past 4 weeks (9–12 weeks) from the baseline phase (4 weeks). The study showed that patients treated with erenumab with both doses experienced 50% or more reduction in monthly migraine days as compared to placebo (70 mg odds ratio [OR]: 2.2, 95% confidence interval [CI]: 1.5–3.3, P = 0.0001; 140 mg OR: 2.3, 95% CI: 1.6–3.5, P < 0.0001).[21] This study also included 453 (68%) patients who had failed at least one previous preventive drug class because of lack of efficacy or poor tolerability and 327 (49%) patients who had failed at least two previous preventive drug classes; results suggest that erenumab may also be helpful in treatment-resistant chronic migraine patients.[24]


  Safety of Erenumab in Chronic Migraine Top


The most common adverse events, reported by 2% or more of erenumab-treated patients, were injection-site pain, upper respiratory tract infection, nausea, nasopharyngitis, constipation, muscle spasms, and migraine, while eight erenumab-treated patients and seven placebo-treated patients showed serious adverse events, but no patient suffering from serious adverse event withdrew from the study. Only two patients from the placebo group and two patients from the erenumab group (140 mg) discontinued from trial because of adverse event.[24] Hypersensitivity reactions, that is, rash, angioedema, and anaphylaxis have been reported in postmarketing surveillance; it is contraindicated in patients showing hypersensitivity reaction.[25]


  Current Status of Erenumab Top


Erenumab has been approved as novel preventive treatment modality; cost of it is approximately $575 (Rs. 39,488) for once monthly 70 single-use prefilled autoinjectors, or $6900 (Rs. 480,038) annually.[26] This cost can hamper the benefit to millions of patients who failed other preventive treatments, especially in developing countries such as India. Currently, it is not available in India; we have to wait and watch for its price and availability in India. Because of their high cost, it should be reserved for patients who have not benefited or are intolerant to other available preventive drugs.


  Conclusion Top


Migraine is a complex, debilitating disease; chronic migraine sufferers spend half of their life enduring pain and physical impairment. For many decades, researchers are trying to find new treatment specifically targeted to complex pathophysiology of migraine. Erenumab is one such drug which could help the patient to live more productive life. Although it is too early to say about its clinical benefit, it has opened the door for a new path for chronic migraine patients.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Cosentino G, Fierro B, Vigneri S, Talamanca S, Paladino P, Baschi R, et al. Cyclical changes of cortical excitability and metaplasticity in migraine: Evidence from a repetitive transcranial magnetic stimulation study. Pain 2014;155:1070-8.  Back to cited text no. 6
    
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Schwedt TJ. Chronic migraine. BMJ 2014;348:g1416.  Back to cited text no. 17
    
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19.
Negro A, Curto M, Lionetto L, Crialesi D, Martelletti P. OnabotulinumtoxinA 155 U in medication overuse headache: A two years prospective study. Springerplus 2015;4:826.  Back to cited text no. 19
    
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New Drug Class Employs Novel Mechanism for Migraine Treatment and Prevention. Available from: https://www.fda.gov/drugs/news -events-human-drugs/new-drug-class-employs-novel-mechanism -migraine-treatment-and-prevention. [Last accessed on 2019 Aug 05].  Back to cited text no. 20
    
21.
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Lassen LH, Haderslev PA, Jacobsen VB, Iversen HK, Sperling B, Olesen J. CGRP may play a causative role in migraine. Cephalalgia 2002;22:54-61.  Back to cited text no. 23
    
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Tepper S, Ashina M, Reuter U, Brandes JL, Doležil D, Silberstein S, et al. Safety and efficacy of erenumab for preventive treatment of chronic migraine: A randomised, double-blind, placebo-controlled phase 2 trial. Lancet Neurol 2017;16:425-34.  Back to cited text no. 24
    
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26.
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  In this article
Abstract
Introduction
Current Manageme...
Erenumab
Efficacy of Eren...
Safety of Erenum...
Current Status o...
Conclusion
References

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