Migraine treatment with biological therapies. The state of the art





Migraine, Treatment, Biological therapies, CGRP, Monoclonal antibodies


Migraine is a highly prevalent and debilitating neurological disorder. Most patients do not receive a correct diagnosis and effective treatments. Apart of the few specialists and tertiary centers worldwide, the treatment of migraine is usually symptomatic and prevention, as well as treatments of the underlying mechanisms, are not aimed. It results in frustration and substantial burden. The last few years witnessed the releasing of specific biological therapies, mostly addressing one of the peptides involved in migraine pathophysiology, the calcitonin gene-related peptide (CGRP). Either the small molecules as well as the monoclonal antibodies against CGRP or its canonical receptor have been launched in markets across the globe and represent interesting options for the treatment of migraine. Onabotulinumtoxin A has also been proposed for chronic migraine as well, but not for episodic migraine, based on its unique ability to inhibit the SNARE complex formation and the release of numerous potential mediators of migraine. However, despite the favorable figures on efficacy and tolerability of these compounds, the regulations, and particulars of different countries, regarding the structures and reimbursement of medical care, demonstrated different adhesion profiles of chosen populations to receive these emerging weapons against migraine-imposed suffering. This review addresses the use and characteristics of biological therapies used in migraine treatment.


Download data is not yet available.


Buse DC, Fanning KM, Reed ML, Murray S, Dumas PK, Adams AM and Lipton RB. Life With Migraine: Effects on Relationships, Career, and Finances From the Chronic Migraine Epidemiology and Outcomes (CaMEO) Study. Headache: The Journal of Head and Face Pain 2019; 59(8): 1286-1299 Doi:10.1111/head.13613 DOI: https://doi.org/10.1111/head.13613

Lipton RB, Bigal ME, Diamond M, Freitag F, Reed ML and Stewart WF. Migraine prevalence, disease burden, and the need for preventive therapy. Neurology 2011; 77(21): 1905-1905 Doi:10.1212/01.wnl.0000407977.35054.34 DOI: https://doi.org/10.1212/01.wnl.0000407977.35054.34

Dodick DW and Silberstein SD. Migraine prevention. Practical Neurology 2007; 7(6): 383-393 Doi:10.1136/jnnp.2007.134023 DOI: https://doi.org/10.1136/jnnp.2007.134023

Silberstein SD. Preventive Migraine Treatment. CONTINUUM: Lifelong Learning in Neurology 2015; 21(973-989 Doi:10.1212/con.0000000000000199 DOI: https://doi.org/10.1212/CON.0000000000000199

The American Headache Society Position Statement On Integrating New Migraine Treatments Into Clinical Practice. Headache: The Journal of Head and Face Pain 2018; Doi:10.1111/head.13456 DOI: https://doi.org/10.1111/head.13456

Blumenfeld AM, Bloudek LM, Becker WJ, Buse DC, Varon SF, Maglinte GA, Lipton RB. 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: The Journal of Head and Face Pain 2013; 53(4): 644-655 Doi:10.1111/head.12055 DOI: https://doi.org/10.1111/head.12055

Hepp Z, Bloudek LM and Varon SF. Systematic Review of Migraine Prophylaxis Adherence and Persistence. Journal of Managed Care Pharmacy 2014; 20(1): 22-33 Doi:10.18553/jmcp.2014.20.1.22 DOI: https://doi.org/10.18553/jmcp.2014.20.1.22

Krymchantowski AV and Jevoux CC. The Pharmacological Treatment of Migraine in Brazil. Headache: The Journal of Head and Face Pain 2015; 55(51-58 Doi:10.1111/head.12513 DOI: https://doi.org/10.1111/head.12513

Gallagher RM and Kunkel R. Migraine Medication Attributes Important for Patient Compliance: Concerns About Side Effects May Delay Treatment. Headache: The Journal of Head and Face Pain 2003; 43(1): 36-43 Doi:10.1046/j.1526-4610.2003.03006.x DOI: https://doi.org/10.1046/j.1526-4610.2003.03006.x

Mitsikostas DD, Belesioti I, Arvaniti C, Mitropoulou E, Deligianni C, Kasioti E, Vikelis M. Patients’ preferences for headache acute and preventive treatment. The Journal of Headache and Pain 2017; 18(1): Doi:10.1186/s10194-017-0813-3 DOI: https://doi.org/10.1186/s10194-017-0813-3

Ashina M, Katsarava Z, Do TP, Buse DC, Pozo-Rosich P, Özge A, . . . Lipton RB. Migraine: epidemiology and systems of care. The Lancet 2021; 397(10283): 1485-1495 Doi:10.1016/s0140-6736(20)32160-7 DOI: https://doi.org/10.1016/S0140-6736(20)32160-7

Krymchantowski AV, Botulinum toxin is not useful for migraine: 2021 [update cited. Available from: https://www.youtube.com/watch?v=KawQdzqiFlE&ab_channel=DrAbouchKrymchantowski.

Krymchantowski A, Silva-Néto RP, Jevoux C and Krymchantowski AG. Brazilian descriptive study of 104 consecutive real-world migraine patients treated with monoclonal antibodies. Postgraduate Medicine 2022; 134(6): 598-602 Doi:10.1080/00325481.2022.2080381 DOI: https://doi.org/10.1080/00325481.2022.2080381

Ferro JKO, Martins JVP, Ribeiro BRCM, Manta TS, Lemos A, Amorim KCS, . . . Oliveira DA. Electromyographic analysis of transversus abdominis/internal oblique muscles during the execution of pelvic patterns of proprioceptive neuromuscular facilitation. Avanços em Medicina 2021; Doi:10.52329/AvanMed.6 DOI: https://doi.org/10.52329/AvanMed.6

Al-Hassany L, Goadsby PJ, Danser AHJ and MaassenVanDenBrink A. Calcitonin gene-related peptide-targeting drugs for migraine: how pharmacology might inform treatment decisions. The Lancet Neurology 2022; 21(3): 284-294 Doi:10.1016/s1474-4422(21)00409-9 DOI: https://doi.org/10.1016/S1474-4422(21)00409-9

Tepper SJ. CGRP and headache: a brief review. Neurological Sciences 2019; 40(S1): 99-105 Doi:10.1007/s10072-019-03769-8 DOI: https://doi.org/10.1007/s10072-019-03769-8

Tepper SJ. History and Review of anti-Calcitonin Gene-Related Peptide (CGRP) Therapies: From Translational Research to Treatment. Headache: The Journal of Head and Face Pain 2018; 58(238-275 Doi:10.1111/head.13379 DOI: https://doi.org/10.1111/head.13379

Dodick DW. CGRP ligand and receptor monoclonal antibodies for migraine prevention: Evidence review and clinical implications. Cephalalgia 2019; 39(3): 445-458 Doi:10.1177/0333102418821662 DOI: https://doi.org/10.1177/0333102418821662

Tso AR and Goadsby PJ. Anti-CGRP Monoclonal Antibodies: the Next Era of Migraine Prevention? Current Treatment Options in Neurology 2017; 19(8): Doi:10.1007/s11940-017-0463-4 DOI: https://doi.org/10.1007/s11940-017-0463-4

Goadsby PJ, Reuter U, Hallström Y, Broessner G, Bonner JH, Zhang F, . . . Lenz RA. A Controlled Trial of Erenumab for Episodic Migraine. New England Journal of Medicine 2017; 377(22): 2123-2132 Doi:10.1056/NEJMoa1705848 DOI: https://doi.org/10.1056/NEJMoa1705848

Dodick DW, Ashina M, Brandes JL, Kudrow D, Lanteri-Minet M, Osipova V, . . . Lenz RA. ARISE: A Phase 3 randomized trial of erenumab for episodic migraine. Cephalalgia 2018; 38(6): 1026-1037 Doi:10.1177/0333102418759786 DOI: https://doi.org/10.1177/0333102418759786

Reuter U, Goadsby PJ, Lanteri-Minet M, Wen S, Hours-Zesiger P, Ferrari MD and Klatt J. 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. The Lancet 2018; 392(10161): 2280-2287 Doi:10.1016/s0140-6736(18)32534-0 DOI: https://doi.org/10.1016/S0140-6736(18)32534-0

Stauffer VL, Dodick DW, Zhang Q, Carter JN, Ailani J and Conley RR. Evaluation of Galcanezumab for the Prevention of Episodic Migraine. JAMA Neurology 2018; 75(9): Doi:10.1001/jamaneurol.2018.1212 DOI: https://doi.org/10.1001/jamaneurol.2018.1212

Skljarevski V, Matharu M, Millen BA, Ossipov MH, Kim B-K and Yang JY. 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(8): 1442-1454 Doi:10.1177/0333102418779543 DOI: https://doi.org/10.1177/0333102418779543

Rosen N, Pearlman E, Ruff D, Day K and Jim Nagy A. 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. Headache: The Journal of Head and Face Pain 2018; 58(9): 1347-1357 Doi:10.1111/head.13427 DOI: https://doi.org/10.1111/head.13427

Camporeale A, Kudrow D, Sides R, Wang S, Van Dycke A, Selzler KJ and Stauffer VL. A phase 3, long-term, open-label safety study of Galcanezumab in patients with migraine. BMC Neurology 2018; 18(1): Doi:10.1186/s12883-018-1193-2 DOI: https://doi.org/10.1186/s12883-018-1193-2

Dodick DW, Silberstein SD, Bigal ME, Yeung PP, Goadsby PJ, Blankenbiller T, . . . Aycardi E. Effect of Fremanezumab Compared With Placebo for Prevention of Episodic Migraine. Jama 2018; 319(19): Doi:10.1001/jama.2018.4853 DOI: https://doi.org/10.1001/jama.2018.4853

Ferrari MD, Diener HC, Ning X, Galic M, Cohen JM, Yang R, . . . Ashina M. 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. The Lancet 2019; 394(10203): 1030-1040 Doi:10.1016/s0140-6736(19)31946-4 DOI: https://doi.org/10.1016/S0140-6736(19)31946-4

Ferrari MD, Zuurbier KWM, Barash S, Ning X and Cohen JM. Fremanezumab in individuals with chronic migraine who had inadequate response to onabotulinumtoxinA and topiramate or valproic acid. Headache: The Journal of Head and Face Pain 2022; 62(4): 530-533 Doi:10.1111/head.14294 DOI: https://doi.org/10.1111/head.14294

Ashina M, Saper J, Cady R, Schaeffler BA, Biondi DM, Hirman J, . . . Smith J. Eptinezumab in episodic migraine: A randomized, double-blind, placebo-controlled study (PROMISE-1). Cephalalgia 2020; 40(3): 241-254 Doi:10.1177/0333102420905132 DOI: https://doi.org/10.1177/0333102420905132

Tepper S, Ashina M, Reuter U, Brandes JL, Doležil D, Silberstein S, . . . Lenz R. Safety and efficacy of erenumab for preventive treatment of chronic migraine: a randomised, double-blind, placebo-controlled phase 2 trial. The Lancet Neurology 2017; 16(6): 425-434 Doi:10.1016/s1474-4422(17)30083-2 DOI: https://doi.org/10.1016/S1474-4422(17)30083-2

Tepper SJ, Ashina M, Reuter U, Brandes JL, Doležil D, Silberstein SD, . . . Mikol DD. Long-term safety and efficacy of erenumab in patients with chronic migraine: Results from a 52-week, open-label extension study. Cephalalgia 2020; 40(6): 543-553 Doi:10.1177/0333102420912726 DOI: https://doi.org/10.1177/0333102420912726

Lipton RB, Tepper SJ, Silberstein SD, Kudrow D, Ashina M, Reuter U, . . . Mikol DD. Reversion from chronic migraine to episodic migraine following treatment with erenumab: Results of a post-hoc analysis of a randomized, 12-week, double-blind study and a 52-week, open-label extension. Cephalalgia 2020; 41(1): 6-16 Doi:10.1177/0333102420973994 DOI: https://doi.org/10.1177/0333102420973994

Detke HC, Goadsby PJ, Wang S, Friedman DI, Selzler KJ and Aurora SK. Galcanezumab in chronic migraine. Neurology 2018; 91(24): e2211-e2221 Doi:10.1212/wnl.0000000000006640 DOI: https://doi.org/10.1212/WNL.0000000000006640

Altamura C, Brunelli N, Marcosano M, Aurilia C, Egeo G, Lovati C, . . . Demirtzidis G. Conversion from chronic to episodic migraine in patients treated with galcanezumab in real life in Italy: the 12-month observational, longitudinal, cohort multicenter GARLIT experience. Journal of Neurology 2022; 269(11): 5848-5857 Doi:10.1007/s00415-022-11226-4 DOI: https://doi.org/10.1007/s00415-022-11226-4

Silberstein SD, Dodick DW, Bigal ME, Yeung PP, Goadsby PJ, Blankenbiller T, . . . Aycardi E. Fremanezumab for the Preventive Treatment of Chronic Migraine. New England Journal of Medicine 2017; 377(22): 2113-2122 Doi:10.1056/NEJMoa1709038 DOI: https://doi.org/10.1056/NEJMoa1709038

Barbanti P, Egeo G, Aurilia C, d’Onofrio F, Albanese M, Cetta I, . . . Vernieri F. Fremanezumab in the prevention of high-frequency episodic and chronic migraine: a 12-week, multicenter, real-life, cohort study (the FRIEND study). The Journal of Headache and Pain 2022; 23(1): Doi:10.1186/s10194-022-01396-x DOI: https://doi.org/10.1186/s10194-022-01434-8

Ornello R, Casalena A, Frattale I, Caponnetto V, Gabriele A, Affaitati G, . . . Sacco S. Conversion from chronic to episodic migraine in patients treated with erenumab: real-life data from an Italian region. The Journal of Headache and Pain 2020; 21(1): Doi:10.1186/s10194-020-01171-w DOI: https://doi.org/10.1186/s10194-020-01171-w

Raffaelli B, Kalantzis R, Mecklenburg J, Overeem LH, Neeb L, Gendolla A and Reuter U. Erenumab in Chronic Migraine Patients Who Previously Failed Five First-Line Oral Prophylactics and OnabotulinumtoxinA: A Dual-Center Retrospective Observational Study. Frontiers in Neurology 2020; 11(Doi:10.3389/fneur.2020.00417 DOI: https://doi.org/10.3389/fneur.2020.00417

Pensato U, Favoni V, Pascazio A, Benini M, Asioli GM, Merli E, . . . Cevoli S. Erenumab efficacy in highly resistant chronic migraine: a real-life study. Neurological Sciences 2020; 41(S2): 457-459 Doi:10.1007/s10072-020-04658-1 DOI: https://doi.org/10.1007/s10072-020-04658-1

60th Annual Scientific Meeting American Headache Society®

June 28-July 1, 2018 San Francisco Marriott Marquis San Francisco, CA. Headache: The Journal of Head and Face Pain 2018; 58(S2): 61-215 Doi:10.1111/head.13306 DOI: https://doi.org/10.1111/head.13306

Burstein R, Blumenfeld AM, Silberstein SD, Manack Adams A and Brin MF. Mechanism of Action of OnabotulinumtoxinA in Chronic Migraine: A Narrative Review. Headache: The Journal of Head and Face Pain 2020; 60(7): 1259-1272 Doi:10.1111/head.13849 DOI: https://doi.org/10.1111/head.13849

Diener HC, Dodick DW, Aurora SK, Turkel CC, DeGryse RE, Lipton RB, . . . Brin MF. OnabotulinumtoxinA for treatment of chronic migraine: Results from the double-blind, randomized, placebo-controlled phase of the PREEMPT 2 trial. Cephalalgia 2010; 30(7): 804-814 Doi:10.1177/0333102410364677 DOI: https://doi.org/10.1177/0333102410364677

Aurora SK, Dodick DW, Turkel CC, DeGryse RE, Silberstein SD, Lipton RB, . . . Brin MF. OnabotulinumtoxinA for treatment of chronic migraine: Results from the double-blind, randomized, placebo-controlled phase of the PREEMPT 1 trial. Cephalalgia 2010; 30(7): 793-803 Doi:10.1177/0333102410364676 DOI: https://doi.org/10.1177/0333102410364676

Mathew NT, Frishberg BM, Gawel M, Dimitrova R, Gibson J and Turkel C. Botulinum Toxin Type A (BOTOX ® ) for the Prophylactic Treatment of Chronic Daily Headache: A Randomized, Double‐Blind, Placebo‐Controlled Trial. Headache: The Journal of Head and Face Pain 2005; 45(4): 293-307 Doi:10.1111/j.1526-4610.2005.05066.x DOI: https://doi.org/10.1111/j.1526-4610.2005.05066.x

Silberstein SD, Stark SR, Lucas SM, Christie SN, Degryse RE and Turkel CC. Botulinum Toxin Type A for the Prophylactic Treatment of Chronic Daily Headache: A Randomized, Double-Blind, Placebo-Controlled Trial. Mayo Clinic Proceedings 2005; 80(9): 1126-1137 Doi:10.4065/80.9.1126 DOI: https://doi.org/10.4065/80.9.1126

Dodick DW, Mauskop A, Elkind AH, DeGryse R, Brin MF and Silberstein SD. Botulinum Toxin Type A for the Prophylaxis of Chronic Daily Headache: Subgroup Analysis of Patients Not Receiving Other Prophylactic Medications: A Randomized Double‐Blind, Placebo‐Controlled Study. Headache: The Journal of Head and Face Pain 2005; 45(4): 315-324 Doi:10.1111/j.1526-4610.2005.05068.x DOI: https://doi.org/10.1111/j.1526-4610.2005.05068.x

Aurora SK, Winner P, Freeman MC, Spierings EL, Heiring JO, DeGryse RE, . . . Turkel CC. OnabotulinumtoxinA for Treatment of Chronic Migraine: Pooled Analyses of the 56-Week PREEMPT Clinical Program. Headache: The Journal of Head and Face Pain 2011; 51(9): 1358-1373 Doi:10.1111/j.1526-4610.2011.01990.x DOI: https://doi.org/10.1111/j.1526-4610.2011.01990.x

Silberstein SD, Dodick DW, Aurora SK, Diener H-C, DeGryse RE, Lipton RB and Turkel CC. Per cent of patients with chronic migraine who responded per onabotulinumtoxinA treatment cycle: PREEMPT. Journal of Neurology, Neurosurgery & Psychiatry 2015; 86(9): 996-1001 Doi:10.1136/jnnp-2013-307149 DOI: https://doi.org/10.1136/jnnp-2013-307149

Martínez-Pías E, Guerrero ÁL, Sierra Á, Trigo J, García-Azorín D. Daily Headache in Chronic Migraine Is a Predictive Factor of Response in Patients Who Had Completed Three Sessions of OnabotulinumtoxinA. Toxins 2021; 13(6): Doi:10.3390/toxins13060432 DOI: https://doi.org/10.3390/toxins13060432

Stovner LJ, Hagen K, Tronvik E, Bruvik Gravdahl G, Burstein R and Dodick DW. FollowTheSutures: Piloting a new way to administer onabotulinumtoxinA for chronic migraine. Cephalalgia 2022; 42(7): 590-597 Doi:10.1177/03331024211067775 DOI: https://doi.org/10.1177/03331024211067775

Ishii R, Schwedt TJ, Dumkrieger G, Lalvani N, Craven A, Goadsby PJ, . . . Dodick DW. Chronic versus episodic migraine: The 15‐day threshold does not adequately reflect substantial differences in disability across the full spectrum of headache frequency. Headache: The Journal of Head and Face Pain 2021; 61(7): 992-1003 Doi:10.1111/head.14154 DOI: https://doi.org/10.1111/head.14154

Torabi SJ, Kasle DA, Savoca EL, Gottschalk CH and Manes RP. Characterizing the providers of and reimbursement for chronic migraine chemodenervation among the Medicare population. Headache: The Journal of Head and Face Pain 2020; 61(2): 373-384 Doi:10.1111/head.14040 DOI: https://doi.org/10.1111/head.14040




How to Cite

Krymchantowski A, Jevoux C, Silva-Néto RP. Migraine treatment with biological therapies. The state of the art. Headache Med [Internet]. 2023 Sep. 30 [cited 2023 Dec. 6];14(3):144-52. Available from: https://headachemedicine.com.br/index.php/hm/article/view/778




Most read articles by the same author(s)

1 2 3 > >>