Real world evidence for CGRP antibodies in migraine prevention

In a topical symposium at #EAN2021, three speakers discussed what is new on targeting CGRP for migraine prevention. Dr Anna Andreou, Kings College London, UK, presented emerging evidence from real world studies for the long-term efficacy and safety of CGRP antibodies as migraine preventives. Professor Dimos-Dimitrios Mitsikostas, National and Kapodistrian University of Athens, Greece, shared cross-trial comparisons of different agents and classes of agent that can provide important information regarding relative efficacy and safety. Although advice on switching therapies is limited, Dr Pablo Irimia Sieira, University of Navarra, Spain, reported real world evidence showing that switching between CGRP antibodies may be worthwhile for some patients with migraine.

CGRP antibodies effective in the real world

Dr Anna Andreou, Kings College London, UK, discussed emerging evidence that calcitonin gene-related peptide (CGRP) antibodies are demonstrated as effective preventive treatments for episodic and chronic migraine in the real world, supporting what is known from randomized clinical trials.1 The average reduction in monthly migraine days (MMD) with CGRP antibodies is around 6-9 days and approximately 40-60% of people get a 50% reduction in MMDs.2-4

CGRP antibodies are demonstrated as effective migraine preventives in the real world

Dr Andreou reflected that while shown to be safe and well-tolerated in the short term, studies are gathering safety data for long term use of CGRP antibodies and further data are needed.1,5,6

Nonetheless, one study does not support discontinuation of CGRP antibodies after 12 months.7 After treatment interruption, migraine frequency rose in most patients over 3 months, and prophylaxis was required again by most patients (N=52).7


CGRP antibodies more likely to help than harm

Professor Dimos-Dimitrios Mitsikostas explained that although there are no head-to-head comparisons of CGRP antibodies with established preventives, cross-trial comparisons can deliver important information. Likelihood to help versus harm (LHH) – the ratio of number needed to treat for a patient to experience an adverse event: number needed to treat for a patient to achieve ≥50% reduction in MMD – was calculated from phase 3 randomized clinical trial data.8

With the LHH analysis, Professor Mitsikostas and colleagues demonstrated that CGRP antibodies exhibit a more favourable benefit:risk ratio than established preventives for episodic and chronic migraine.8

CGRP antibodies exhibit a more favourable benefit:risk ratio than older migraine preventives


Rationale for switching CGRP antibodies

Dr Pablo Irimia Sieira discussed approaches to individualizing preventive treatment in clinical practice. By the time people with migraine are placed on a CGRP antibody they typically have failed several other preventive medications.9 Among people who have tried one of the older migraine preventives, many do not adhere to treatment due to poor tolerability, lack of efficacy or both.10-12

Clinical decision making should take into account patient preferences and personal experience alongside the best available scientific evidence

There is limited guidance on switching CGRP antibodies in non-responders due to a lack of data from randomized studies or registries, although a 2020 update to the German Society of Neurology guidelines suggests that an attempt to change CGRP therapy is justified.13

Differences between CGRP antibodies support the rationale for switching. Failure to respond to a monoclonal antibody against CGRP ligand or its receptor does not preclude lack of efficacy to another drug from the same therapeutic class.14 And switching medications is routinely done with other classes of medications for migraines.

For 30% of patients who do not respond first time, a switch to a second CGRP antibody may be worthwhile

In a retrospective analysis of refractory migraine patients (N=121), when patients were switched from one CGRP antibody to another due to lack of efficacy or side effects, around one-third did well on the second CGRP antibody.9

Our correspondent’s highlights from the symposium are meant as a fair representation of the scientific content presented. The views and opinions expressed on this page do not necessarily reflect those of Lundbeck.


  1. Ashina M, et al. Long-term efficacy and safety of erenumab in migraine prevention: Results from a 5-year, open-label treatment phase of a randomized clinical trial. Eur J Neurol 2021;28(5):1716–25.
  2. Lambru G, et al. A prospective real-world analysis of erenumab in refractory chronic migraine. J Headache Pain. 2020;21(1):61.
  3. Robblee J, et al. Real-world patient experience with erenumab for the preventive treatment of migraine. Headache 2020;60(9):2014–25.
  4. Ornello R, et al. Real-life data on the efficacy and safety of erenumab in the Abruzzo region, central Italy. J Headache Pain. 2020;21(1):32.
  5. Ashina M, et al. Long-term safety and tolerability of erenumab: Three-plus year results from a five-year open-label extension study in episodic migraine. Cephalalgia 2019;39(11):1455–64.
  6. Goadsby PJ, et al. Long-term safety, tolerability, and efficacy of fremanezumab in migraine: A randomized study. Neurology 2020;95(18):e2487–e2499.
  7. Gantenbein AR, et al. Impact on monthly migraine days of discontinuing anti-CGRP antibodies after one year of treatment – a real-life cohort study. Cephalalgia 2021;May doi:10.1177/03331024211014616
  8. Drellia K, et al. Anti-CGRP monoclonal antibodies for migraine prevention: A systematic review and likelihood to help or harm analysis Cephalalgia. 2021;41(7):851–64.
  9. Robbins L. CGRP monoclonal antibodies for chronic migraine: year 1 of clinical use. Practical Pain Management 2019;19(6):58–62.
  10. Berger A, et al. Adherence with migraine prophylaxis in clinical practice. Pain Pract 2012;12:541–9.
  11. Hepp Z, et al. Persistence and switching patterns of oral migraine prophylactic medications among patients with chronic migraine: A retrospective claims analysis. Cephalalgia 2017;37:470–85.
  12. Blumenfeld AM, et al. 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 2013;53(4):644–55.
  13. Diener HC, 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.
  14. Porta-Etessam J, et al. Failure to monoclonal antibodies against CGRP or its receptor does not preclude lack of efficacy to other drugs from the same therapeutic class [Spanish]. Neurologia 2020; Nov 8: