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CGRP and headache: a brief review

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Abstract

The advent of anti-CGRP medications is an example of translational research made real. Pioneering research by Drs. Lars Edvinsson and Peter Goadsby has yielded the monoclonal antibody therapeutics and will likely also result in the gepants. The availability of MABs represents a watershed moment in the treatment of migraine. These medications have specificity, as they were designed for primary migraine prevention. They work across a group of wide therapeutic targets, episodic migraine, chronic migraine, medication-overuse headache, and episodic cluster headache. They separate from placebo within 1 week, and often show clinical effects within a month or less. They have tolerability similar to placebo. There has been no significant or worrisome safety signal thus far in their use. They manifest unprecedented responder rates at ≥ 75% and even 100%. They lower all acute medication use and can convert patients from chronic migraine to episodic migraine and from acute medication overuse to non-overuse. They work in patients who have already had lack of success with at least 2–4 previous preventive medications. Pent-up demand for designer, well-tolerated, and effective migraine preventive medication in the USA has resulted in more than 100,000 individual patients prescribed erenumab from May to December of 2018, and the numbers continue to increase. The preventive treatment of migraine in the USA has shifted dramatically, and is likely to do so in the rest of the world as well.

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References

  1. Edvinsson L (2005) Clinical data on the CGRP antagonist BIBN4096BS for treatment of migraine attacks. CNS Drug Rev 11:69–76

    Article  CAS  PubMed  Google Scholar 

  2. Olesen J, Diener HC, Husstedt IW, Goadsby PJ, Hall D, Meier U, Pollentier S, Lesko LM, BIBN 4096 BS Clinical Proof of Concept Study Group (2004) Calcitonin gene-related peptide receptor antagonist BIBN 4096 BS for the acute treatment of migraine. N Engl J Med 350:1104–1110

    Article  CAS  PubMed  Google Scholar 

  3. Lipton RB, Coric V, Stock EG, Stock D, Morris BA, McCormack T, Frost M, Gentile K, Conway CM, Croop R (2018) Efficacy, safety, and tolerability of rimegepant 75 mg, an oral CGRP receptor antagonist, for the acute treatment of migraine: results from a double-blind, randomized, placebo-controlled trial, Study 301. Poster PS123LB. Late breaking abstracts, American Headache Society 60th scientific meeting, San Francisco, CA, June 2018. Headache 58:1336–1337 (abstract)

    Google Scholar 

  4. Lipton RB, Coric V, Stock EG, Stock D, Morris BA, McCormack T, Frost M, Gentile K, Conway CM, Croop R (2018) Efficacy, safety, and tolerability of rimegepant 75 mg, an oral CGRP receptor antagonist, for the acute treatment of migraine: results from a double-blind, randomized, placebo-controlled trial, Study 302. Poster IOR-02LB. Late breaking abstracts, American Headache Society 60th scientific meeting, San Francisco, CA, June 2018. Headache 58:1289 (abstract)

    Google Scholar 

  5. Lipton RB, Dodick DW, Ailani J, Lu K, Lakkis H, Finnegan M, Szegedi A, Trugman JM (2018) Efficacy, safety, and tolerability of ubrogepant for the acute treatment of migraine: results from a single attack phase III study, ACHIEVE II. Poster PS111B. Late breaking abstracts, American Headache Society 60th scientific meeting, San Francisco, CA, June 2018. Headache 58:1315–1316 (abstract)

    Google Scholar 

  6. Trugman J, Finnegan M, Lipton R, Dodick D, Lu K, Lakkis H, Szegedi A (2018) Efficacy, Safety, and Tolerability of ubrogepant for the acute treatment of migraine: results from a single attack phase II study, ACHIEVE I. Emerging Science Platform Presentation 008, American Academy of Neurology meeting, Los Angeles, April 24, 2018. Neurology 90(24):e2186 (abstract)

    Google Scholar 

  7. Tfelt-Hansen P, Loder E (2019) The Emperor’s new gepants: are the effects of the new oral CGRP antagonists clinically meaningful? Headache 59:113–117

    Article  PubMed  Google Scholar 

  8. Available at: https://www.prnewswire.com/news-releases/allergans-oral-cgrp-receptor-antagonist-atogepant-demonstrates-robust-efficacy-and-safety-in-episodic-migraine-prevention-in-a-phase-2b3-clinical-trial-300663770.html. Accessed 13 June 2018

  9. Rimegepant in development for acute treatment and prevention of migraine. Available at: Biohavenpharma.com. Accessed 4 July 2018

  10. Goadsby PJ, Reuter U, Hallström Y, Broessner G, Bonner JH, Zhang F, Sapra S, Picard H, Mikol DD, Lenz RA (2017) A controlled trial of Erenumab for episodic migraine. N Engl J Med 377:2123–2132

    Article  CAS  PubMed  Google Scholar 

  11. Dodick DW, Ashina M, Brandes JL, Kudrow D, Lanteri-Minet M, Osipova V, Palmer K, Picard H, Mikol DD, Lenz RA (2018) ARISE: a phase 3 randomized trial of erenumab for episodic migraine. Cephalalgia 38:1026–1037

    Article  PubMed  Google Scholar 

  12. Reuter U, Goadsby PJ, Lanteri-Minet M, Wen S, Hours-Zesiger P, Ferrari MD, Klatt J (2018) 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 392(10161):2280–2287

    Article  CAS  PubMed  Google Scholar 

  13. Ashina M, Dodick D, Goadsby PJ, Reuter U, Silberstein S, Zhang F, Gage JR, Cheng S, Mikol DD, Lenz RA (2017) Erenumab (AMG 334) in episodic migraine: interim analysis of an ongoing open-label study. Neurology 89:1237–1243

    Article  CAS  PubMed  Google Scholar 

  14. Dodick DW, Silberstein SD, Bigal ME, Yeung PP, Goadsby PJ, Blankenbiller T, Grozinski-Wolff M, Yang R, Ma Y, Aycardi E (2018) Effect of fremanezumab compared with placebo for prevention of episodic migraine: a randomized clinical trial. JAMA 319:1999–2008

    Article  CAS  PubMed  Google Scholar 

  15. Stauffer VL, Dodick DW, Zhang Q, Carter JN, Ailani J, Conley RR (2018) Evaluation of galcanezumab for the prevention of episodic migraine: the EVOLVE-1 ran-domized clinical trial. JAMA Neurol 75:1080–1088

    Article  PubMed  PubMed Central  Google Scholar 

  16. Skljarevski V, Matharu M, Millen BA, Ossipov MH, Kim BK, Yang JY (2018) Efficacy and safety of galcanezumab for the prevention of episodic migraine: results of the EVOLVE-2 phase 3 randomized controlled clinical trial. Cephalalgia 38:1442–1454

    Article  PubMed  Google Scholar 

  17. Rosen N, Pearlman E, Ruff D, Day K, Jim Nagy A (2018) 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 58:1347–1357

    Article  PubMed  PubMed Central  Google Scholar 

  18. Camporeale A, Kudrow D, Sides R, Wang S, Van Dycke A, Selzler KJ, Stauffer VL (2018) A phase 3, long-term, open-label safety study of galcanezumab in patients with migraine. BMC Neurol 18:188

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Saper J, Lipton R, Kudrow D, Hirman J, Dodick D, Silberstein S, Chakhava G, Smith J (2018) Primary results of PROMISE-1 (Prevention Of Migraine via Intravenous eptinezumab Safety and Efficacy–1) trial: a phase 3, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of eptinezumab for prevention of frequent episodic migraines. Neurology 90(15S):S20 (abstract)

    Google Scholar 

  20. Tepper S, Ashina M, Reuter U, Brandes JL, Dolezil D, Silberstein S, Winner P, Leonardi D, Mikol D, Lenz R (2017) Safety and efficacy of erenumab for preventive treatment of chronic migraine: a randomised, double-blind, placebo-controlled phase 2 trial. Lancet Neurol 16:425–434

    Article  CAS  PubMed  Google Scholar 

  21. Tepper SJ, Ashina M, Reuter U, Brandes JL, Dolezil D, Silberstein S, Winner P, Zhang F, Cheng S, Mikol DD (2018) Assessment of the long-term safety and efficacy of erenumab during open-label treatment of subjects with chronic migraine. Late-breaking Abstract Poster PF115LB and E-Poster presentation, 60th American Headache Society Scientific Meeting, San Francisco, CA, June 28–29, 2018; E-Poster presentation, Poster P24, 12th European Headache Federation Congress, Florence, Italy, Sept 28, 2018. Headache 58:1302–1303 (abstract)

    Google Scholar 

  22. Tepper SJ (2018) Anti-calcitonin gene-related peptide (CGRP) therapies: update on a previous review after the American Headache Society 60th scientific meeting, San Francisco, CA, June 2018. Headache 58 (Supplement 3:276–290

    Article  Google Scholar 

  23. Lipton RB, Tepper SJ, Silberstein SD, Kudrow D, Ashina M, Dodick D, Zhang F, Rippon G, Mikol D (2018) Conversion from chronic to episodic migraine with erenumab, a specific inhibitor of the calcitonin gene-related peptide receptor. Poster PS25. Headache 58(Supplement 2):162–163 (abstract)

    Google Scholar 

  24. Tepper S, Lipton RB, Silberstein S, Kudrow D, Ashina M, Reuter U, Dodick D, Zhang F, Cheng S, Mikol DD (2018) Long-term efficacy of erenumab in chronic migraine patients with acute medication overuse. Late-breaking Abstract Poster PF 109LB and E-Poster presentation, 60th American Headache Society Scientific Meeting, San Francisco, June 28–29, 2018A (abstract). Headache 58:1298–1299 (abstract)

    Google Scholar 

  25. Silberstein SD, Dodick DW, Bigal ME, Yeung PP, Goadsby PJ, Blankenbiller T, Grozinski-Wolff M, Yang R, Ma Y, Aycardi E (2017) Fremanezumab for the preventive treatment of chronic migraine. N Engl J Med 377:2113–2122

    Article  CAS  PubMed  Google Scholar 

  26. Brandes J, Yeung PP, Cohen JM, Gandhi SK, Fitzgerald T, Yang R, Ma Y, Aycardi E (2018) Long-term impact of fremanezumab on response rates, acute headache medication use, and disability in patients with episodic migraine: Interim results of a one-year study. Poster PS35. Headache 58(Supplement 2):170 (abstract)

    Google Scholar 

  27. Detke HC, Goadsby PJ, Wang S, Friedman DI, Selzler KJ, Aurora SK (2018) Galcanezumab in chronic migraine: the randomized, double-blind, placebo-controlled REGAIN study. Neurology 91(24):e2211–e2221

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Lipton RB, Saper J, Ashina M, Biondi B, Bhattacharya S, Hirman J, Schaeffler B, Cady R (2018) A phase 3, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of eptinezumab for the preventive treatment of chronic migraine: results of the PROMISE-2 (Prevention Of Migraine via Intravenous eptinezumab Safety and Efficacy-2) trial. Platform presentation. American Academy of Neurology meeting, Los Angeles, CA, April 24, 2018. (abstract)

  29. Silberstein S, Spierings ELH, Berman G, Biondi D, Smith J, Bhattacharya S, Cady R (2018) Eptinezumab reduced migraine frequency and triptan/ergotamine use over weeks 1–12, and improved HIT-6 scores at months 1 and 3: results from the phase 3 PROMISE-2 trial in chronic migraine. P4-471. American Academy of Neurology meeting, Los Angeles, CA, April 25, 2018. (abstract)

  30. Kudrow D, Diamond M, McGill L, Cady, R, Bhattachrya S, Biondi D, Hirman J, Smith J (2018) Eptinezumab achieved meaningful reductions in migraine activity as early as day 1 that were sustained through week 12: results from PROMISE-2(Prevention of migraine via intravenous eptinezumab safety and Efficacy-2) phase 3 trial in chronic migraine. P4–470. American Academy of Neurology meeting, April 2018. (abstract)

  31. Maassen van den Brink A, Meijer J, Villalon CM, Ferrari MD (2016) Wiping out CGRP: potential cardiovascular risks. Trends Pharmacol Sci 37:779–788

    Article  CAS  Google Scholar 

  32. Chaitman BR, Ho AP, Behm MO, Rowe JF, Palcza JS, Laethem T, Heirman I, Panebianco DL, Kobalava Z, Martsevich SY, Free AL, Bittar N, Chrysant SG, Ho TW, Chodakewitz JA, Murphy MG, Blanchard RL (2012) A randomized, placebo-controlled study of the effects of telcagepant on exercise time in patients with stable angina. Clin Pharmacol Ther 91:459–466

    Article  CAS  PubMed  Google Scholar 

  33. Depre C, Antalik L, Starling A, Koren M, Eisele O, Lenz RA, Mikol DD (2018) A randomized, double-blind, placebo-controlled study to evaluate the effect of erenumab on exercise time during a treadmill test in patients with stable angina. Headache 58:715–723

    Article  PubMed  PubMed Central  Google Scholar 

  34. Conway CM, Dubowchik GM, Coric V (2018) Rimegepant and BHV-3500, small molecule CGRP receptor antagonists, exhibit no active vasoconstrictive properties in ex vivo human coronary or cerebral arteries. Poster LBOR-08. Late breaking abstracts, American Headache Society 60th scientific meeting, San Francisco, CA, June 2018. Headache 58:1295 (abstract)

    Google Scholar 

  35. Maassen van den Brink A, Labastida-Ramírez A, Bogers A, Danser AHJ, Snellman J, Xu C, Rubio-Beltrán E (2018) Pharmacological selectivity of inhibition of CGRP induced relaxations by erenumab studied in human isolated internal mammary artery. Poster PS114LB. Late breaking abstracts, American Headache Society 60th scientific meeting, San Francisco, CA, June 2018. Headache 58:1317–1318 (abstract)

    Article  Google Scholar 

  36. Pascual J, Dolezil D, Davies B, Picard H, Hong F, Zhang F, Xue F, Mikol D, Klatt J (2018) Analysis of injection site reactions across four placebo controlled trials of erenumab for migraine prevention. P4.116. Neurology. 2018;90 (Supplement 15). American Academy of Neurology meeting, Los Angeles, CA, April 10, 2018. (abstract)

  37. Ning X, Faulhaber N, Lang N, Yeung PP, Schiemann CJM, Aycardi E (2018) Fremanezumab cardiovascular safety profile: pooled data from placebo-controlled and long-term studies. Poster PS41. Headache 58(Supplement 2):174–175 (abstract)

    Google Scholar 

  38. Fiedler-Kelly J, Passarell C, Passarell J, Faulhaber N, Yeung PP, Aycardi E, Cohen-Barak O, Levi M (2018) Lack of relationship between fremanezumab exposure and cardiovascular adverse events in phase 2 and 3 data including chronic and episodic migraine patients. Poster PS47. Headache 58(Supplement 2):178–179 (abstract)

    Google Scholar 

  39. Tepper SJ (2018) History and review of anti-calcitonin gene-related peptide (CGRP) therapies: from translational research to treatment. Headache 58(Supplement 3):238–275

    Article  PubMed  Google Scholar 

  40. Martinez JM, Goadsby P, Dodick D, Bardos JN, Myers O, Tina M, Millen BA, Dowsett SA ZC, Aurora SK, Conley RR, Yang JU (2018) Study CGAL: a phase 3 placebo-controlled study of galcanezumab in patients with episodic cluster headache: results from the 8-week double -blind treatment phase. Poster IOR-03LB. Late breaking abstracts, American Headache Society 60th scientific meeting, San Francisco, CA, June 2018. Headache 58(8):1289–1290 (abstract)

    Google Scholar 

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Authors and Affiliations

  1. Neurology Department, Dartmouth-Hitchcock Medical Center, 1 Medical Center Drive, Lebanon, NH, 03756, USA

    Stewart J. Tepper

  2. Geisel School of Medicine at Dartmouth, Hanover, NH, USA

    Stewart J. Tepper

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Correspondence to Stewart J. Tepper.

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Grants for research (no personal compensation): Alder, Allergan, Amgen, ATI, Dr. Reddy’s, ElectroCore, eNeura, Neurolief, Scion Neurostim, Teva, Zosano.

Consultant and/or Advisory Boards: Acorda, Alder, Alexsa, Allergan, Alphasights, Amgen, ATI, Axsome Therapeutics, Biohaven, Cefaly, Charleston Labs, DeepBench, Dr. Reddy’s, ElectroCore, Eli Lilly, eNeura, ExpertConnect, GLG, Guidepoint Global, GSK, Impel, Magellan Rx Management, Navigant Consulting, Neurolief, Nordic BioTech, Novartis, Pfizer, Reckner Healthcare, Satsuma, Scion Neurostim, Slingshot Insights, Sorrento, Sudler and Hennessey, Supernus, Teva, Theranica, Trinity Partners, XOC, Zosano.

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Salary: Dartmouth-Hitchcock Medical Center, American Headache Society.

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Tepper, S.J. CGRP and headache: a brief review. Neurol Sci 40 (Suppl 1), 99–105 (2019). https://doi.org/10.1007/s10072-019-03769-8

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