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Neurology and Therapy
Published in: Neurology and Therapy 3/2022

Open Access 15-06-2022 | Migraine | Original Research

Atogepant for the Prevention of Episodic Migraine in Adults: A Systematic Review and Meta-Analysis of Efficacy and Safety

Authors: Simona Lattanzi, Eugen Trinka, Claudia Altamura, Cinzia Del Giovane, Mauro Silvestrini, Francesco Brigo, Fabrizio Vernieri

Published in: Neurology and Therapy | Issue 3/2022

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Abstract

Introduction

The inhibition of the calcitonin gene-related peptide (CGRP) pathway has attracted interest in pharmacological research on migraine. Atogepant is a potent, selective, orally available antagonist of the CGRP receptor approved as a preventive treatment of episodic migraine. This systematic review with meta-analysis aims to evaluate the efficacy and safety of atogepant for the prevention of episodic migraine in adult patients.

Methods

Randomized, placebo-controlled, single or double-blinded trials were identified through a systematic literature search (December week 4, 2021). Main outcomes included the changes from baseline in monthly migraine days and the incidence of adverse events (AEs) and treatment withdrawal due to AEs. Mean difference (MD) and risk ratio (RR) with 95% confidence intervals (95% CIs) were estimated.

Results

Two trials were included, overall enrolling 1550 patients. A total of 408 participants were randomized to placebo, 314 to atogepant 10 mg, 411 to atogepant 30 mg, and 417 to atogepant 60 mg once daily. The mean age of the patients was 41.0 years and 87.7% were women. The reduction in the mean number of migraine days from baseline across the 12-week treatment period was significantly greater among patients treated with atogepant at either the daily dose of 10 mg (MD − 1.16, 95% CI − 1.60 to − 0.73, p < 0.001), 30 mg (MD − 1.15, 95% CI − 1.54 to − 0.76, p < 0.001), or 60 mg (MD − 1.20, 95% CI − 2.18 to − 0.22, p = 0.016) than with placebo. There were no differences in the occurrence of AEs and drug withdrawal due to AEs between atogepant and placebo groups. Constipation was more commonly observed in patients treated with atogepant at 30 mg/day than placebo (RR 5.19, 95% CI 2.00–13.46; p = 0.001). Treatment with atogepant at the daily dose of 60 mg was associated with a higher risk of constipation (RR 4.92, 95% CI 1.89–12.79; p = 0.001) and nausea (RR 2.73, 95% CI 1.47–5.06; p = 0.001) than placebo.

Conclusion

Atogepant is an efficacious and overall well-tolerated treatment for the prevention of episodic migraine in adults.
Appendix
Available only for authorised users
Literature
1.
Vos T, Flaxman AD, Naghavi M, et al. Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012;380:2163–96.PubMedPubMedCentralCrossRef
2.
Headache Classification Committee of the International Headache Society. The international classification of headache disorders, 3rd edition (beta version). Cephalalgia. 2013;33:629–808.CrossRef
3.
Buse DC, Rupnow MF, Lipton RB. Assessing and managing all aspects of migraine: migraine attacks, migraine-related functional impairment, common comorbidities, and quality of life. Mayo Clin Proc. 2009;84:422–35.PubMedPubMedCentralCrossRef
4.
Serrano D, Manack AN, Reed ML, Buse DC, Varon SF, Lipton RB. Cost and predictors of lost productive time in chronic migraine and episodic migraine: results from the American Migraine Prevalence and Prevention (AMPP) Study. Value Health. 2013;16:31–8.PubMedCrossRef
5.
Stokes M, Becker WJ, Lipton RB, et al. Cost of health care among patients with chronic and episodic migraine in Canada and the USA: results from the International Burden of Migraine Study (IBMS). Headache. 2011;51:1058–77.PubMedCrossRef
6.
Bloudek LM, Stokes M, Buse DC, et al. Cost of healthcare for patients with migraine in five European countries: results from the International Burden of Migraine Study (IBMS). J Headache Pain. 2012;13:361–78.PubMedPubMedCentralCrossRef
7.
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.PubMedCrossRef
8.
Lassen LH, Jacobsen VB, Haderslev PA, et al. Involvement of calcitonin gene-related peptide in migraine: regional cerebral blood flow and blood flow velocity in migraine patients. J Headache Pain. 2008;9:151–7.PubMedPubMedCentralCrossRef
9.
Ashina M, Bendtsen L, Jensen R, Schifter S, Olesen J. Evidence for increased plasma levels of calcitonin gene-related peptide in migraine outside of attacks. Pain. 2000;86:133–8.PubMedCrossRef
10.
Cernuda-Morollon E, Larrosa D, Ramon C, Vega J, Martinez-Camblor P, Pascual J. Interictal increase of CGRP levels in peripheral blood as a biomarker for chronic migraine. Neurology. 2013;81:1191–6.PubMedCrossRef
11.
Cady RK, Vause CV, Ho TW, Bigal ME, Durham PL. Elevated saliva calcitonin gene-related peptide levels during acute migraine predict therapeutic response to rizatriptan. Headache. 2009;49:1258–66.PubMedCrossRef
12.
Cady R, Turner I, Dexter K, Beach ME, Cady R, Durham P. An exploratory study of salivary calcitonin gene-related peptide levels relative to acute interventions and preventative treatment with onabotulinumtoxinA in chronic migraine. Headache. 2014;54:269–77.PubMedCrossRef
13.
14.
Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6:e1000097.PubMedPubMedCentralCrossRef
15.
16.
17.
Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21:1539–58.PubMed
18.
Lattanzi S, Trinka E, Zaccara G, et al. Adjunctive cenobamate for focal-onset seizures in adults: a systematic review and meta-analysis. CNS Drugs. 2020;34:1105–20.PubMedPubMedCentralCrossRef
19.
Lattanzi S, Brigo F, Trinka E, et al. Adjunctive cannabidiol in patients with Dravet syndrome: a systematic review and meta-analysis of efficacy and safety. CNS Drugs. 2020;34:229–41.PubMedCrossRef
20.
Lattanzi S, Trinka E, Striano P, et al. Cannabidiol efficacy and clobazam status: a systematic review and meta-analysis. Epilepsia. 2020;61:1090–8.PubMedCrossRef
21.
Lattanzi S, Brigo F, Cagnetti C, Di Napoli M, Silvestrini M. Patent foramen ovale and cryptogenic stroke or transient ischemic attack: to close or not to close? A systematic review and meta-analysis. Cerebrovasc Dis. 2018;45:193–203.PubMedCrossRef
22.
Lattanzi S, Grillo E, Brigo F, Silvestrini M. Efficacy and safety of perampanel in Parkinson’s disease. A systematic review with meta-analysis. J Neurol. 2018;265:733–40.PubMedCrossRef
23.
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;19:727–37.PubMedCrossRef
24.
Ailani J, Lipton RB, Goadsby PJ, et al. Atogepant for the preventive treatment of migraine. N Engl J Med. 2021;385:695–706.PubMedCrossRef
25.
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.PubMedCrossRef
26.
Schwedt T, Reuter U, Tepper S, et al. Early onset of efficacy with erenumab in patients with episodic and chronic migraine. J Headache Pain. 2018;19:92.PubMedPubMedCentralCrossRef
27.
28.
Winner PK, Spierings ELH, Yeung PP, et al. Early onset of efficacy with fremanezumab for the preventive treatment of chronic migraine. Headache. 2019;59:1743–52.PubMedCrossRef
29.
Dodick DW, Gottschalk C, Cady R, et al. Eptinezumab demonstrated efficacy in sustained prevention of episodic and chronic migraine beginning on day 1 after dosing. Headache. 2020;60:2220–31.PubMedPubMedCentralCrossRef
30.
Lattanzi S, Brigo F, Trinka E, et al. Erenumab for preventive treatment of migraine: a systematic review and meta-analysis of efficacy and safety. Drugs. 2019;79:417–31.PubMedCrossRef
31.
Silberstein SD, Neto W, Schmitt J, Jacobs D, MIGR-001 Study Group. Topiramate in migraine prevention: results of a large controlled trial. Arch Neurol. 2004;61:490–5.PubMedCrossRef
32.
Brandes JL, Saper JR, Diamond M, et al. Topiramate for migraine prevention: a randomized controlled trial. JAMA. 2004;291:965–73.PubMedCrossRef
33.
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.PubMedCrossRef
34.
35.
Diener HC, Förderreuther S, Gaul C, et al. Prevention of migraine with monoclonal antibodies against CGRP or the CGRP receptor: addition to the S1 guideline: therapy of migraine attacks and prevention of migraine. Recommendations of the Germany Society of Neurology and the German Migraine and Headache Society. Neurol Res Pract. 2020;2:11.PubMedPubMedCentralCrossRef
36.
Jansen I, Uddman R, Hocherman M, et al. Localization and effects of neuropeptide Y, vasoactive intestinal polypeptide, substance P, and calcitonin gene-related peptide in human temporal arteries. Ann Neurol. 1986;20:496–501.PubMedCrossRef
37.
Mulderry PK, Ghatei MA, Spokes RA, et al. Differential expression of alpha-CGRP and beta-CGRP by primary sensory neurons and enteric autonomic neurons of the rat. Neuroscience. 1988;25:195–205.PubMedCrossRef
38.
Falkenberg K, Bjerg HR, Olesen J. Two-hour CGRP infusion causes gastrointestinal hyperactivity: possible relevance for CGRP antibody treatment. Headache. 2020;60:929–37.PubMedCrossRef
39.
Barbanti P, Aurilia C, Egeo G, et al. Erenumab in the prevention of high-frequency episodic and chronic migraine: erenumab in real life in Italy (EARLY), the first Italian multicenter, prospective real-life study. Headache. 2021;61:363–72.PubMedCrossRef
40.
Barbanti P, Aurilia C, Cevoli S, et al. Long-term (48 weeks) effectiveness, safety, and tolerability of erenumab in the prevention of high-frequency episodic and chronic migraine in a real world: results of the EARLY 2 study. Headache. 2021;61:1351–63.PubMedCrossRef
41.
Hay DL, Garelja ML, Poyner DR, Walker CS. Update on the pharmacology of calcitonin/CGRP family of peptides: IUPHAR review 25. Br J Pharmacol. 2018;175:3–17.PubMedCrossRef
42.
Negro A, Martelletti P. Gepants for the treatment of migraine. Expert Opin Investig Drugs. 2019;28:555–67.PubMedCrossRef
43.
Min KC, Kraft WK, Bondiskey P, et al. Atogepant is not associated with clinically meaningful alanine aminotransferase elevations in healthy adults. Clin Transl Sci. 2021;14:599–605.PubMedCrossRef
44.
45.
Rubio-Beltran E, Chan KY, Danser AJ, et al. Characterisation of the calcitonin gene-related peptide receptor antagonists ubrogepant and atogepant in human isolated coronary, cerebral and middle meningeal arteries. Cephalalgia. 2020;40:357–66.PubMedCrossRef
46.
Petersen KA, Birk S, Lassen LH, et al. The CGRP-antagonist, BIBN4096BS does not affect cerebral or systemic haemodynamics in healthy volunteers. Cephalalgia. 2005;25:139–47.PubMedCrossRef
47.
Van der Schueren BJ, Blanchard R, Murphy MG, et al. The potent calcitonin gene-related peptide receptor antagonist, telcagepant, does not affect nitroglycerin-induced vasodilation in healthy men. Br J Clin Pharmacol. 2011;71:708–17.PubMedPubMedCentralCrossRef
48.
49.
Tao X, Yan Z, Meng J, et al. The efficacy and safety of atogepant for the prophylactic treatment of migraine: evidence from randomized controlled trials. J Headache Pain. 2022;23:19.PubMedPubMedCentralCrossRef
50.
Singh A, Balasundaram MK. Atogepant for migraine prevention: a systematic review of efficacy and safety. Clin Drug Investig. 2022;42:301–8.PubMedCrossRef
51.
Rustichelli C, Avallone R, Ferrari A. Atogepant: an emerging treatment for migraine. Expert Opin Pharmacother. 2022;23:653–62.PubMedCrossRef
52.
Cohen F, Yuan H. Role of atogepant in the treatment of episodic migraines: clinical perspectives and considerations. Ther Clin Risk Manag. 2022;18:447–56.PubMedPubMedCentralCrossRef
53.
Al-Hassany L, Van Den Brink AM. Targeting CGRP in migraine: a matter of choice and dose. Lancet Neurol. 2020;19:712–3.PubMedCrossRef
54.
Ashina M, Tepper SJ, Reuter U, et al. Atogepant 60 mg once-daily shows efficacy for the preventive treatment of migraine: results from a 52-week open-label extension trial [abstract no. P-133]. Headache. 2021;61(Suppl 1). https://​doi.​org/​10.​1111/​head.​14130.
55.
Lipton RB, Halker Singh RB, Mechtler LL, et al. Daily dosing of atogepant for preventive treatment of migraine improved patient reported outcomes measures of migraine-specific quality of life, activity impairment in migraine-diary, and headache-impact test in a 52-week trial [abstract no. P-203]. Headache. 2021;61(Suppl 1):119–20.
56.
57.
Martelletti P, Cipolla F, Capi M, Curto M, Lionetto L. Atogepant. Calcitonin gene-related peptide (CGRP) receptor antagonist, preventive treatment of migraine. Drugs Future. 2020;45:285.CrossRef
Metadata
Title
Atogepant for the Prevention of Episodic Migraine in Adults: A Systematic Review and Meta-Analysis of Efficacy and Safety
Authors
Simona Lattanzi
Eugen Trinka
Claudia Altamura
Cinzia Del Giovane
Mauro Silvestrini
Francesco Brigo
Fabrizio Vernieri
Publication date
15-06-2022
Publisher
Springer Healthcare
Published in
Neurology and Therapy / Issue 3/2022
Print ISSN: 2193-8253
Electronic ISSN: 2193-6536
DOI
https://doi.org/10.1007/s40120-022-00370-8

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