Skip to main content
Top
Published in: Current Pain and Headache Reports 5/2018

01-05-2018 | Chronic Daily Headache (S.J. Wang, Section editor)

CGRP Monoclonal Antibodies for the Preventative Treatment of Migraine

Authors: Heike Israel, Lars Neeb, Uwe Reuter

Published in: Current Pain and Headache Reports | Issue 5/2018

Login to get access

Abstract

Purpose of Review

CGRP is a key neuropeptide in migraine pathophysiology. The blockade of the CGRP pathway at the side of the CGRP receptor of the CGRP peptide leads to the interruption of trigeminal nerve system-mediated headache syndromes such as migraine. Monoclonal antibodies (mAbs) targeting the CGRP pathway have been developed and are currently under investigation for episodic (EM) and chronic migraine (CM) prevention. Here, we report data from these clinical trials.

Recent Findings

Placebo-controlled, randomized double-blind phase studies of CGRP mAbs in episodic and chronic migraine have shown that the specific blockade of the peptide or the CGRP receptor are both powerful mechanisms to reduce migraine frequency. Along with the reduction of acute migraine-specific medication intake, early onset of efficacy of mAbs has been demonstrated. Most common adverse events are injection sider reactions. Depending on the mAb, the administration mode is a monthly or even less frequently s.c. or I.V. formulation.

Summary

Phase II studies in EM and CM demonstrate that CGRP mAbs are effective anti-migraine preventatives with a beneficial adverse event profile. Further detailed results from larger phase III clinical trials are expected soon.
Literature
1.
go back to reference • Mitsikostas DD, Reuter U. Calcitonin gene-related peptide monoclonal antibodies for migraine prevention: comparisons across randomized controlled studies. Curr Opin Neurol. 2017;30:272–80.CrossRefPubMed • Mitsikostas DD, Reuter U. Calcitonin gene-related peptide monoclonal antibodies for migraine prevention: comparisons across randomized controlled studies. Curr Opin Neurol. 2017;30:272–80.CrossRefPubMed
3.
go back to reference Smillie SJ, Brain SD. Calcitonin gene-related peptide (CGRP) and its role in hypertension. Neuropeptides. 2011;45:93–104.CrossRefPubMed Smillie SJ, Brain SD. Calcitonin gene-related peptide (CGRP) and its role in hypertension. Neuropeptides. 2011;45:93–104.CrossRefPubMed
5.
go back to reference Hepp Z, Dodick DW, Varon SF, Gillard P, Hansen RN, Devine EB. Adherence to oral migraine-preventive medications among patients with chronic migraine. Cephalalgia. 2015;35(6):478–88.CrossRefPubMed Hepp Z, Dodick DW, Varon SF, Gillard P, Hansen RN, Devine EB. Adherence to oral migraine-preventive medications among patients with chronic migraine. Cephalalgia. 2015;35(6):478–88.CrossRefPubMed
6.
go back to reference Peres MF, Silberstein S, Moreira F, Corchs F, Vieira DS, Abraham N, et al. Patients’ preference for migraine preventive therapy. Headache. 2007;47:540–5.CrossRefPubMed Peres MF, Silberstein S, Moreira F, Corchs F, Vieira DS, Abraham N, et al. Patients’ preference for migraine preventive therapy. Headache. 2007;47:540–5.CrossRefPubMed
7.
go back to reference Kowacs PA, Piovesan EJ, Tepper SJ. Rejection and acceptance of possible side effects of migraine prophylactic drugs. Headache. 2009;49:1022–7.CrossRefPubMed Kowacs PA, Piovesan EJ, Tepper SJ. Rejection and acceptance of possible side effects of migraine prophylactic drugs. Headache. 2009;49:1022–7.CrossRefPubMed
8.
go back to reference Lipton RB, Manack Adams A, Buse DC, Fanning KM, Reed ML. A comparison of the Chronic Migraine Epidemiology and Outcomes (CaMEO) study and American Migraine Prevalence and Prevention (AMPP) study: demographics and headache-related disability. Headache. 2016;56:1280–9.CrossRefPubMedPubMedCentral Lipton RB, Manack Adams A, Buse DC, Fanning KM, Reed ML. A comparison of the Chronic Migraine Epidemiology and Outcomes (CaMEO) study and American Migraine Prevalence and Prevention (AMPP) study: demographics and headache-related disability. Headache. 2016;56:1280–9.CrossRefPubMedPubMedCentral
9.
go back to reference Blumenfeld AM, Bloudek LM, Becker WJ, Buse DC, Varon SF, Maglinte GA, et al. Patterns of use and reasons for discontinuation of prophylactic medications for episodic migraine and chronic migraine: results from the Second International Burden Of Migraine Study (IBMS-II). Headache. 2013;53:644–55.CrossRefPubMed Blumenfeld AM, Bloudek LM, Becker WJ, Buse DC, Varon SF, Maglinte GA, et al. Patterns of use and reasons for discontinuation of prophylactic medications for episodic migraine and chronic migraine: results from the Second International Burden Of Migraine Study (IBMS-II). Headache. 2013;53:644–55.CrossRefPubMed
10.
go back to reference •• Bigal ME, Edvinsson L, Rapoport AM, Lipton RB, Spierings EL, Diener HC, et al. Safety, tolerability, and efficacy of TEV-48125 for preventive treatment of chronic migraine: a multicentre, randomised, double-blind, placebo-controlled, phase 2b study. Lancet Neurol. 2015;14:1091–100. The first phase II trial of a mAbs CGRP receptor antagonist for chronic migraine prevention. CrossRefPubMed •• Bigal ME, Edvinsson L, Rapoport AM, Lipton RB, Spierings EL, Diener HC, et al. Safety, tolerability, and efficacy of TEV-48125 for preventive treatment of chronic migraine: a multicentre, randomised, double-blind, placebo-controlled, phase 2b study. Lancet Neurol. 2015;14:1091–100. The first phase II trial of a mAbs CGRP receptor antagonist for chronic migraine prevention. CrossRefPubMed
11.
go back to reference Cohen JM, Dodick DW, Yang R, Newman LC, Li T, Aycardi E, et al. Fremanezumab as add-on treatment for patients treated with other migraine preventive medicines. Headache. 2017;57:1375–84.CrossRefPubMed Cohen JM, Dodick DW, Yang R, Newman LC, Li T, Aycardi E, et al. Fremanezumab as add-on treatment for patients treated with other migraine preventive medicines. Headache. 2017;57:1375–84.CrossRefPubMed
12.
go back to reference Silberstein SD, Dodick DW, Lindblad AS, Holroyd K, Harrington M, Mathew NT, et al. Randomized, placebo-controlled trial of propranolol added to topiramate in chronic migraine. Neurology. 2012;78:976–84.CrossRefPubMedPubMedCentral Silberstein SD, Dodick DW, Lindblad AS, Holroyd K, Harrington M, Mathew NT, et al. Randomized, placebo-controlled trial of propranolol added to topiramate in chronic migraine. Neurology. 2012;78:976–84.CrossRefPubMedPubMedCentral
13.
go back to reference Bigal ME, Dodick DW, Krymchantowski AV, VanderPluym JH, Tepper SJ, Aycardi E, et al. TEV-48125 for the preventive treatment of chronic migraine: efficacy at early time points. Neurology. 2016;87:41–8.CrossRefPubMedPubMedCentral Bigal ME, Dodick DW, Krymchantowski AV, VanderPluym JH, Tepper SJ, Aycardi E, et al. TEV-48125 for the preventive treatment of chronic migraine: efficacy at early time points. Neurology. 2016;87:41–8.CrossRefPubMedPubMedCentral
14.
go back to reference •• 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. The first phase II trial of a mAbs CGRP receptor antagonist for chronic migraine prevention. CrossRefPubMed •• 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. The first phase II trial of a mAbs CGRP receptor antagonist for chronic migraine prevention. CrossRefPubMed
15.
go back to reference •• Goadsby PJ, Reuter U, Hallström Y, Broessner G, Bonner JH, Zhang F, et al. A controlled trial of erenumab for episodic migraine. N Engl J Med. 2017;377(22):2123–32. The first phase III trial of a mAbs CGRP receptor antagonist for migraine prevention. CrossRefPubMed •• Goadsby PJ, Reuter U, Hallström Y, Broessner G, Bonner JH, Zhang F, et al. A controlled trial of erenumab for episodic migraine. N Engl J Med. 2017;377(22):2123–32. The first phase III trial of a mAbs CGRP receptor antagonist for migraine prevention. CrossRefPubMed
16.
go back to reference •• Dodick DW, Goadsby PJ, Spierings EL, Scherer JC, Sweeney SP, Grayzel DS. Safety and efficacy of LY2951742, a monoclonal antibody to calcitonin gene-related peptide, for the prevention of migraine: a phase 2, randomised, double-blind, placebo-controlled study. Lancet Neurol. 2014;13:885–92. The first phase II trial of a mAbs CGRP antagonist for migraine prevention. CrossRefPubMed •• Dodick DW, Goadsby PJ, Spierings EL, Scherer JC, Sweeney SP, Grayzel DS. Safety and efficacy of LY2951742, a monoclonal antibody to calcitonin gene-related peptide, for the prevention of migraine: a phase 2, randomised, double-blind, placebo-controlled study. Lancet Neurol. 2014;13:885–92. The first phase II trial of a mAbs CGRP antagonist for migraine prevention. CrossRefPubMed
17.
go back to reference Dodick DW, Goadsby PJ, Silberstein SD, Lipton RB, Olesen J, Ashina M, et al. Safety and efficacy of ALD403, an antibody to calcitonin gene-related peptide, for the prevention of frequent episodic migraine: a randomized, double blind, placebo-controlled, exploratory phase 2 trial. Lancet Neurol. 2014;13:1100–7.CrossRefPubMed Dodick DW, Goadsby PJ, Silberstein SD, Lipton RB, Olesen J, Ashina M, et al. Safety and efficacy of ALD403, an antibody to calcitonin gene-related peptide, for the prevention of frequent episodic migraine: a randomized, double blind, placebo-controlled, exploratory phase 2 trial. Lancet Neurol. 2014;13:1100–7.CrossRefPubMed
18.
go back to reference Bigal ME, Dodick DW, Rapoport AM, Silberstein SD, Ma Y, Yang R, et al. Safety, tolerability, and efficacy of TEV-48125 for preventive treatment of high-frequency episodic migraine: a multicenter, randomized, double-blind, placebo-controlled, phase 2b study. Lancet Neurol. 2015;14:1081–90.CrossRefPubMed Bigal ME, Dodick DW, Rapoport AM, Silberstein SD, Ma Y, Yang R, et al. Safety, tolerability, and efficacy of TEV-48125 for preventive treatment of high-frequency episodic migraine: a multicenter, randomized, double-blind, placebo-controlled, phase 2b study. Lancet Neurol. 2015;14:1081–90.CrossRefPubMed
19.
go back to reference •• Sun H, Dodick DW, Silberstein S, Goadsby PJ, Reuter U, Ashina M, et al. Safety and efficacy of AMG 334 for prevention of episodic migraine: a randomized, double-blind, placebo-controlled, phase 2 trial. Lancet Neurol. 2016;15:382–9. The first phase II trial of a mAbs CGRP receptor antagonist for migraine prevention. CrossRefPubMed •• Sun H, Dodick DW, Silberstein S, Goadsby PJ, Reuter U, Ashina M, et al. Safety and efficacy of AMG 334 for prevention of episodic migraine: a randomized, double-blind, placebo-controlled, phase 2 trial. Lancet Neurol. 2016;15:382–9. The first phase II trial of a mAbs CGRP receptor antagonist for migraine prevention. CrossRefPubMed
20.
go back to reference Bendtsen L, Mattsson P, Zwart JA, Lipton RB. Placebo response in clinical randomized trials of analgesics in migraine. Cephalalgia. 2003;23:487–90.CrossRefPubMed Bendtsen L, Mattsson P, Zwart JA, Lipton RB. Placebo response in clinical randomized trials of analgesics in migraine. Cephalalgia. 2003;23:487–90.CrossRefPubMed
21.
go back to reference Reuter U. Anti-CGRP antibodies: a new approach to migraine prevention. Lancet Neurol. 2014;13(9):857–9.CrossRefPubMed Reuter U. Anti-CGRP antibodies: a new approach to migraine prevention. Lancet Neurol. 2014;13(9):857–9.CrossRefPubMed
22.
go back to reference Ashina M, Dodick D, Goadsby PJ, Reuter U, Silberstein S, Zhang F, et al. Erenumab (AMG 334) in episodic migraine: interim analysis of an ongoing open-label study. Neurology. 2017;89:1237–43.CrossRefPubMed Ashina M, Dodick D, Goadsby PJ, Reuter U, Silberstein S, Zhang F, et al. Erenumab (AMG 334) in episodic migraine: interim analysis of an ongoing open-label study. Neurology. 2017;89:1237–43.CrossRefPubMed
23.
go back to reference •• Silberstein SD, Dodick DW, Bigal ME, Yeung PP, Goadsby PJ, Blankenbiller T, et al. Fremanezumab for the preventive treatment of chronic migraine. N Engl J Med. 2017;377(22):2113–22. The first phase III trial of a mAbs CGRP antagonist for chronic migraine prevention.CrossRefPubMed •• Silberstein SD, Dodick DW, Bigal ME, Yeung PP, Goadsby PJ, Blankenbiller T, et al. Fremanezumab for the preventive treatment of chronic migraine. N Engl J Med. 2017;377(22):2113–22. The first phase III trial of a mAbs CGRP antagonist for chronic migraine prevention.CrossRefPubMed
24.
go back to reference Vécsei L, Majláth Z, Szok D, Csáti A, Tajti J. Drug safety and tolerability in prophylactic migraine treatment. Expert Opin Drug Saf. 2015;14:667–81.CrossRefPubMed Vécsei L, Majláth Z, Szok D, Csáti A, Tajti J. Drug safety and tolerability in prophylactic migraine treatment. Expert Opin Drug Saf. 2015;14:667–81.CrossRefPubMed
25.
go back to reference Silberstein SD, Lipton RB, Dodick DW, Freitag FG, Ramadan N, Mathew N, et al. Efficacy and safety of topiramate for the treatment of chronic migraine: a randomized, double-blind, placebo-controlled trial. Headache. 2007;47:170–80.CrossRefPubMed Silberstein SD, Lipton RB, Dodick DW, Freitag FG, Ramadan N, Mathew N, et al. Efficacy and safety of topiramate for the treatment of chronic migraine: a randomized, double-blind, placebo-controlled trial. Headache. 2007;47:170–80.CrossRefPubMed
26.
go back to reference Aurora SK, Dodick DW, Turkel CC, DeGryse RE, Silberstein SD, Lipton RB, et al. Onabotulinumtoxin for treatment of chronic migraine: results from the double blind, randomized, placebo-controlled phase of the PREEMPT 1 trial. Cephalalgia. 2010;30:793–803.CrossRefPubMed Aurora SK, Dodick DW, Turkel CC, DeGryse RE, Silberstein SD, Lipton RB, et al. Onabotulinumtoxin for treatment of chronic migraine: results from the double blind, randomized, placebo-controlled phase of the PREEMPT 1 trial. Cephalalgia. 2010;30:793–803.CrossRefPubMed
27.
go back to reference Diener HC, Dodick DW, Aurora SK, Turkel CC, DeGryse RE, Lipton RB, et al. Onabotulinumtoxin A for treatment of chronic migraine: results from the double-blind, randomized, placebo-controlled phase of the PREEMPT 2 trial. Cephalalgia. 2010;30:804–14.CrossRefPubMed Diener HC, Dodick DW, Aurora SK, Turkel CC, DeGryse RE, Lipton RB, et al. Onabotulinumtoxin A for treatment of chronic migraine: results from the double-blind, randomized, placebo-controlled phase of the PREEMPT 2 trial. Cephalalgia. 2010;30:804–14.CrossRefPubMed
28.
go back to reference Deen M, Correnti E, Kamm K, Kelderman T, Papetti L, Rubio-Beltrán E, et al. Blocking CGRP in migraine patients—a review of pros and cons. J Headache Pain. 2017;18:96.CrossRefPubMedPubMedCentral Deen M, Correnti E, Kamm K, Kelderman T, Papetti L, Rubio-Beltrán E, et al. Blocking CGRP in migraine patients—a review of pros and cons. J Headache Pain. 2017;18:96.CrossRefPubMedPubMedCentral
29.
go back to reference Chaitman BR, Ho AP, Behm MO, Rowe JF, Palcza JS, Laethem T, et al. A randomized, placebo-controlled study of the effects of telcagepant on exercise time in patients with stable angina. Clin Pharmacol Ther. 2012;91:459–66.CrossRefPubMed Chaitman BR, Ho AP, Behm MO, Rowe JF, Palcza JS, Laethem T, et al. A randomized, placebo-controlled study of the effects of telcagepant on exercise time in patients with stable angina. Clin Pharmacol Ther. 2012;91:459–66.CrossRefPubMed
Metadata
Title
CGRP Monoclonal Antibodies for the Preventative Treatment of Migraine
Authors
Heike Israel
Lars Neeb
Uwe Reuter
Publication date
01-05-2018
Publisher
Springer US
Published in
Current Pain and Headache Reports / Issue 5/2018
Print ISSN: 1531-3433
Electronic ISSN: 1534-3081
DOI
https://doi.org/10.1007/s11916-018-0686-4

Other articles of this Issue 5/2018

Current Pain and Headache Reports 5/2018 Go to the issue

Migraine and Beyond (R Cowan, Section Editor)

Is Migraine Primarily a Metaboloendocrine Disorder?

Other Pain (A Kaye and N Vadivelu, Section Editors)

Evidence-Based Non-Pharmacological Therapies for Fibromyalgia

Other Pain (A Kaye and N Vadivelu, Section Editors)

New Advances in Acute Postoperative Pain Management

Other Pain (A Kaye and N Vadivelu, Section Editors)

Global Supply and Demand of Opioids for Pain Management