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DOI: 10.1055/a-2276-2239
Anti-CGRP basierte Migränemedikamente – eine Übersicht der Studienlage
Anti-CGRP-based Migraine Medications: A Comprehensive OverviewZusammenfassung
Seit Anfang der 1990er Jahre ist bekannt, dass das Neuropeptid Calcitonin Gene-Related Peptid (CGRP) eine Schlüsselrolle in der Pathophysiologie der Migräne spielt. Mit dieser Entdeckung ergaben sich in der Migränetherapie neue Angriffspunkte für Medikamente, die in den letzten Jahren unser therapeutisches Arsenal revolutioniert haben. Während bisherige Prophylaktika relativ unspezifisch wirkten und mit oft nicht tolerablen Nebenwirkungen einhergingen, entstanden mit CGRP als Zielstruktur in der Migräneprophylaxe gut verträgliche und hocheffektive neue Therapieoptionen. Die zwei Hauptklassen der CGRP-spezifischen Migränetherapie sind monoklonale Antikörper, die CGRP oder den CGRP-Rezeptor binden und Gepante, CGRP-Rezeptor Antagonisten, die aufgrund ihrer molekularen Eigenschaften die intrazelluläre Signaltransmission blockieren. In großen Zulassungsstudien konnte die Sicherheit, Verträglichkeit und Wirksamkeit von monoklonalen CGRP-Antikörpern in der prophylaktischen Therapie der episodischen und chronischen Migräne nachgewiesen werden. Gleiches gilt für den Einsatz verschiedener Gepante, die sich in der Akuttherapie als Alternative zu Triptanen und bei kontinuierlicher Einnahme als Prophylaktika in klinischen Studien als effektiv und sicher herausstellten. In dieser Übersichtsarbeit möchten wir den aktuellen Stand der Forschung zur CGRP-spezifischen Migränetherapie und Erkenntnisse aus ersten Anwendungsdaten darlegen.
Abstract
In the early 1990s, the neuropeptide calcitonin gene-related peptide (CGRP) was identified as a key messenger in the pathophysiology of migraine and emerged as a treatment target, fundamentally transforming our approach to migraine therapy. While previous prophylactic drugs were non-specific and often caused intolerable side effects, the discovery of CGRP marked the advent of a new era in migraine treatment. The two main classes of CGRP-specific migraine treatments are monoclonal antibodies that bind to CGRP or the CGRP receptor, and CGRP receptor antagonists, the so-called gepants. Extensive clinical trials have conclusively demonstrated the safety, tolerability, and efficacy of monoclonal CGRP(-receptor) antibodies in the prophylactic treatment of both episodic and chronic migraine. The same positive results apply to the use of various gepants. They have proven to be not only an effective alternative to triptans in acute migraine therapy but also promising options for continuous use as prophylactic treatments. In this review, we aim to present the current state of research on CGRP-specific migraine therapy and insights in real-world data from the first years after their launch in clinical practice.
Publication History
Received: 04 September 2023
Accepted after revision: 19 February 2024
Article published online:
28 March 2024
© 2024. Thieme. All rights reserved.
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Literatur
- 1 Ashina M. Migraine. N Engl J Med 2020; 383: 1866-1876 DOI: 10.1056/NEJMra1915327.
- 2 Moreno-Ajona D, Villar-Martínez MD, Goadsby PJ. New Generation Gepants: Migraine Acute and Preventive Medications. J Clin Med 2022; 11 DOI: 10.3390/jcm11061656.
- 3 Lipton RB, Croop R, Stock EG. et al. Rimegepant, an Oral Calcitonin Gene-Related Peptide Receptor Antagonist, for Migraine. N Engl J Med 2019; 381: 142-149 DOI: 10.1056/NEJMoa1811090.
- 4 Croop R, Goadsby PJ, Stock DA. et al. Efficacy, safety, and tolerability of rimegepant orally disintegrating tablet for the acute treatment of migraine: a randomised, phase 3, double-blind, placebo-controlled trial. Lancet 2019; 394: 737-745 DOI: 10.1016/s0140-6736(19)31606-x.
- 5 Croop R, Lipton RB, Kudrow D. et al. Oral rimegepant for preventive treatment of migraine: a phase 2/3, randomised, double-blind, placebo-controlled trial. The Lancet 2021; 397: 51-60 DOI: 10.1016/S0140-6736(20)32544-7.
- 6 Dodick DW, Lipton RB, Ailani J. et al. Ubrogepant for the Treatment of Migraine. New England Journal of Medicine 2019; 381: 2230-2241 DOI: 10.1056/NEJMoa1813049.
- 7 Lipton RB, Dodick DW, Ailani J. et al. Effect of Ubrogepant vs Placebo on Pain and the Most Bothersome Associated Symptom in the Acute Treatment of Migraine: The ACHIEVE II Randomized Clinical Trial. Jama 2019; 322: 1887-1898 DOI: 10.1001/jama.2019.16711.
- 8 Goadsby PJ, Dodick DW, Ailani J. et al. Safety, tolerability, and efficacy of orally administered atogepant for the prevention of episodic migraine in adults: a double-blind, randomised phase 2b/3 trial. Lancet Neurol 2020; 19: 727-737 DOI: 10.1016/s1474-4422(20)30234-9.
- 9 Schwedt TJ, Lipton RB, Ailani J. et al. Time course of efficacy of atogepant for the preventive treatment of migraine: Results from the randomized, double-blind ADVANCE trial. Cephalalgia 2022; 42: 3-11 DOI: 10.1177/03331024211042385.
- 10 Pozo-Rosich P, Ailani J, Ashina M. et al. Atogepant for the preventive treatment of chronic migraine (PROGRESS): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 2023; DOI: 10.1016/s0140-6736(23)01049-8.
- 11 Croop R, Madonia J, Stock DA. et al. Zavegepant nasal spray for the acute treatment of migraine: A Phase 2/3 double-blind, randomized, placebo-controlled, dose-ranging trial. Headache 2022; 62: 1153-1163 DOI: 10.1111/head.14389.
- 12 Goadsby PJ, Reuter U, Hallström Y. et al. A Controlled Trial of Erenumab for Episodic Migraine. N Engl J Med 2017; 377: 2123-2132 DOI: 10.1056/NEJMoa1705848.
- 13 Dodick DW, Ashina M, Brandes JL. et al. ARISE: A Phase 3 randomized trial of erenumab for episodic migraine. Cephalalgia 2018; 38: 1026-1037 DOI: 10.1177/0333102418759786.
- 14 Tepper S, Ashina M, Reuter U. 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: 425-434 DOI: 10.1016/s1474-4422(17)30083-2.
- 15 Reuter U, Goadsby PJ, Lanteri-Minet M. et al. Efficacy and tolerability of erenumab in patients with episodic migraine in whom two-to-four previous preventive treatments were unsuccessful: a randomised, double-blind, placebo-controlled, phase 3b study. Lancet 2018; 392: 2280-2287 DOI: 10.1016/s0140-6736(18)32534-0.
- 16 Goadsby PJ, Reuter U, Lanteri-Minet M. et al. Long-Term Efficacy and Safety of Erenumab: Results From 64 Weeks of the LIBERTY Study. Neurology 2021; 96: e2724-e2735 DOI: 10.1212/wnl.0000000000012029.
- 17 Reuter U, Ehrlich M, Gendolla A. et al. Erenumab versus topiramate for the prevention of migraine – a randomised, double-blind, active-controlled phase 4 trial. Cephalalgia 2022; 42: 108-118 DOI: 10.1177/03331024211053571.
- 18 Dodick DW, Silberstein SD, Bigal ME. et al. Effect of Fremanezumab Compared With Placebo for Prevention of Episodic Migraine: A Randomized Clinical Trial. Jama 2018; 319: 1999-2008 DOI: 10.1001/jama.2018.4853.
- 19 Silberstein SD, Dodick DW, Bigal ME. et al. Fremanezumab for the Preventive Treatment of Chronic Migraine. N Engl J Med 2017; 377: 2113-2122 DOI: 10.1056/NEJMoa1709038.
- 20 Ferrari MD, Diener HC, Ning X. et al. Fremanezumab versus placebo for migraine prevention in patients with documented failure to up to four migraine preventive medication classes (FOCUS): a randomised, double-blind, placebo-controlled, phase 3b trial. Lancet 2019; 394: 1030-1040 DOI: 10.1016/s0140-6736(19)31946-4.
- 21 Stauffer VL, Dodick DW, Zhang Q. et al. Evaluation of Galcanezumab for the Prevention of Episodic Migraine: The EVOLVE-1 Randomized Clinical Trial. JAMA Neurol 2018; 75: 1080-1088 DOI: 10.1001/jamaneurol.2018.1212.
- 22 Skljarevski V, Matharu M, Millen BA. et al. Efficacy and safety of galcanezumab for the prevention of episodic migraine: Results of the EVOLVE-2 Phase 3 randomized controlled clinical trial. Cephalalgia 2018; 38: 1442-1454 DOI: 10.1177/0333102418779543.
- 23 Detke HC, Goadsby PJ, Wang S. et al. Galcanezumab in chronic migraine: The randomized, double-blind, placebo-controlled REGAIN study. Neurology 2018; 91: e2211-e2221 DOI: 10.1212/wnl.0000000000006640.
- 24 Mulleners WM, Kim BK, Láinez MJA. et al. Safety and efficacy of galcanezumab in patients for whom previous migraine preventive medication from two to four categories had failed (CONQUER): a multicentre, randomised, double-blind, placebo-controlled, phase 3b trial. Lancet Neurol 2020; 19: 814-825 DOI: 10.1016/s1474-4422(20)30279-9.
- 25 Ashina M, Saper J, Cady R. et al. Eptinezumab in episodic migraine: A randomized, double-blind, placebo-controlled study (PROMISE-1). Cephalalgia 2020; 40: 241-254 DOI: 10.1177/0333102420905132.
- 26 Lipton RB, Goadsby PJ, Smith J. et al. Efficacy and safety of eptinezumab in patients with chronic migraine: PROMISE-2. Neurology 2020; 94: e1365-e1377 DOI: 10.1212/wnl.0000000000009169.
- 27 Ashina M, Lanteri-Minet M, Pozo-Rosich P. et al. Safety and efficacy of eptinezumab for migraine prevention in patients with two-to-four previous preventive treatment failures (DELIVER): a multi-arm, randomised, double-blind, placebo-controlled, phase 3b trial. Lancet Neurol 2022; 21: 597-607 DOI: 10.1016/s1474-4422(22)00185-5.
- 28 Raffaelli B, Kalantzis R, Mecklenburg J. et al. Erenumab in Chronic Migraine Patients Who Previously Failed Five First-Line Oral Prophylactics and OnabotulinumtoxinA: A Dual-Center Retrospective Observational Study. Front Neurol 2020; 11: 417 DOI: 10.3389/fneur.2020.00417.
- 29 de Vries Lentsch S, van der Arend BWH, Maassen VanDenBrink A. et al. Blood Pressure in Patients With Migraine Treated With Monoclonal Anti-CGRP (Receptor) Antibodies: A Prospective Follow-up Study. Neurology 2022; 99: e1897-e1904 DOI: 10.1212/wnl.0000000000201008.
- 30 Raffaelli B, Terhart M, Overeem LH. et al. Migraine evolution after the cessation of CGRP(-receptor) antibody prophylaxis: a prospective, longitudinal cohort study. Cephalalgia 2022; 42: 326-334 DOI: 10.1177/03331024211046617.
- 31 Overeem LH, Lange KS, Fitzek MP. et al. Effect of switching to erenumab in non-responders to a CGRP ligand antibody treatment in migraine: A real-world cohort study. Front Neurol 2023; 14: 1154420 DOI: 10.3389/fneur.2023.1154420.
- 32 Hong JB, Lange KS, Overeem LH. et al. A Scoping Review and Meta-Analysis of Anti-CGRP Monoclonal Antibodies: Predicting Response. Pharmaceuticals (Basel) 2023; 16 DOI: 10.3390/ph16070934.