CGRP-targeted antibodies in difficult-to-treat migraine

Article metrics


A new study shows that the monoclonal antibody fremanezumab is effective for migraine prophylaxis, even in patients who have failed to respond to multiple preventive treatments. However, not all patients benefit from this treatment, and detailed investigation of non-responders could help to identify additional pharmacological targets and increase the number of responders.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Fig. 1: Determinants of response to anti-CGRP antibodies.


  1. 1.

    Edvinsson, L., Villalon, C. M. & MaassenVanDenBrink, A. Basic mechanisms of migraine and its acute treatment. Pharmacol. Ther. 136, 319–333 (2012).

  2. 2.

    Reuter, U. 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 392, 2280–2287 (2018).

  3. 3.

    Ashina, M. et al. Efficacy and safety of erenumab (AMG334) in chronic migraine patients with prior preventive treatment failure: a subgroup analysis of a randomized, double-blind, placebo-controlled study. Cephalalgia 38, 1611–1621 (2018).

  4. 4.

    Ferrari, M. D. 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 394, 1030–1040 (2019).

  5. 5.

    Silberstein, S. D. et al. Fremanezumab for the preventive treatment of chronic migraine. N. Engl. J. Med. 377, 2113–2122 (2017).

  6. 6.

    Dodick, D. W. et al. Effect of fremanezumab compared with placebo for prevention of episodic migraine: a randomized clinical trial. JAMA 319, 1999–2008 (2018).

  7. 7.

    Sacco, S. et al. European Headache Federation guideline on the use of monoclonal antibodies acting on the calcitonin gene related peptide or its receptor for migraine prevention. J. Headache Pain 20, 6 (2019).

  8. 8.

    MaassenVanDenBrink, A., Meijer, J., Villalon, C. M. & Ferrari, M. D. Wiping out CGRP: potential cardiovascular risks. Trends Pharmacol. Sci. 37, 779–788 (2016).

  9. 9.

    Depre, C. et al. 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 (2018).

  10. 10.

    Maassen van den Brink, A., Rubio-Beltran, E., Duncker, D. & Villalon, C. M. Is CGRP receptor blockade cardiovascularly safe? Appropriate studies are needed. Headache 58, 1257–1258 (2018).

Download references

Author information

Correspondence to Antoinette MaassenVanDenBrink.

Ethics declarations

Competing interests

A.M. has received research grants and/or consultation fees from Amgen/Novartis, Lilly/CoLucid, Teva and Autonomic Technologies, Inc. (ATI). T.d.V. declares no competing interests.

Rights and permissions

Reprints and Permissions

About this article