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#296 Frequent migraines are a headache: Can biologics help?


CLINICAL QUESTION
QUESTION CLINIQUE
 What is the efficacy of Calcitonin Gene Related Peptide (CGRP) inhibitors in migraine prophylaxis?

BOTTOM LINE
RÉSULTAT FINAL
 For patients with episodic and chronic migraines, treating 5-8 patients with a CGRP-inhibitor will lead to one patient experiencing at least a 50% reduction in monthly migraine days compared to placebo. From baseline, a decrease of 1-2 monthly migraine days may be seen. Cost may limit use.


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EVIDENCE
DONNÉES PROBANTES
  • Results statistically significant unless otherwise stated. Studies in episodic and chronic migraines.
    • Erenumab (Aimovig®) 70-140mg subcutaneously monthly versus placebo:
      • 1 systematic review [5 randomized controlled trials (RCTs), 2928 patients, 9-18 monthly migraine days, 84% female, mean 41 years old, duration 12 weeks].1
        • Achieving at least 50% reduction in monthly migraine days:
          • 70mg dose: 42% versus 27% (placebo) [number needed to treat (NNT)=7].
          • 140mg dose: 40% versus 21% (placebo) (NNT=5).
        • Reduction of monthly migraines: 1.5-2.0 days.
    • Galcanezumab (Emgality®) 120-240mg subcutaneously monthly versus placebo:
      • 1 systematic review (3 RCTs, 2886 patients, 9-19 monthly migraine days, 85% female, mean ~41 years old, duration 12-24 weeks).2
        • Achieving at least a 50% reduction in monthly migraine days:
          • 41% versus 26% (placebo) (NNT=7).
        • Reduction of monthly migraines: 1.9 days.
    • Fremanezumab (Ajovy®) 675mg subcutaneously every 3 months versus placebo:
      • 5 RCT (3379 patients, ~16 monthly migraine days, mean 41 years old).3
        • Achieving at least 50% reduction in monthly migraine days:
          • 41% versus 19% (placebo) (NNT=5).
        • Reduction of monthly migraines: 2.2 days.
    • Other systematic reviews found similar.4-6
    • Adverse events: No difference except for injection site pain (11% versus 8.1% placebo).1,2,4,7 
    • Limitations: Short duration studies (12-24 weeks) for a chronic condition. Sustained efficacy and long-term safety unknown. Trials often excluded patients who failed more than 2-3 medication groups. Majority RCTs industry sponsored.
Context
  • Other medications with evidence of benefit:
    • Achieving >50% reduction in monthly migraine days: Propranolol (NNT=4)8, tricyclic antidepressants (NNT=5).9
    • Headache frequency reduction over placebo: Candesartan (~1.5 days), topiramate (~1 day).8,10 
  • Cost for CGRP-inhibitors in Canada is ~$7000/year.11
  • Guidelines12,13 recommend a trial of at least 2 oral agents prior to CGRP-inhibitors.

Peter Kuling August 26, 2021

less costly alternatives as effective

Martin Withers January 1, 2022

Good update

Sanjiv Anand January 15, 2022

Good alternative to treating migraines if first line treatments not working

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August 23, 2021

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Author(s)
Auteur(s)
  • Sandra Trkulja BScPharm PharmD
  • Trudy Huyghebaert PharmD
  • Joey Ton PharmD
  • Clark Svrcek MD CCFP

1. Zhu C, Guan J, Xiao H, et al. Medicine (Baltimore). 2019 Dec; 98(52):e18483.

2. Förderreuther S, Zhang Q, Stauffer VL, et al. J Headache Pain. 2018 Dec 29; 19(1):121.

3. Gao B, Sun N, Yang Y, et al. Front Neurol . 2020 May 19; 11:435.

4. Deng H, Li G, Nie H, et al. BMC Neurol. 2020 Feb 15; 20(1):57.

5. Wang X, Chen Y, Song J, et al. Front Pharmacol. 2021 Mar 25; 12:649143.

6. Lattanzi S, Brigo F, Trinka E, et al. Drugs. 2019 Mar 1; 79, 417–431.

7. Reuter U, Goadsby PJ, Lanteri-Minet M, et al. Lancet. 2018 Nov 24; 392(10161):2280-2287.

8. Kapusta M, Allan GM. Tools for Practice #52. Available at: https://gomainpro.ca/wp-content/uploads/tools-for-practice/1433184708_updatedtfp52antihypertensivesmigraineprophylaxis.pdf. Last accessed: July 21, 2021.

9. Allan GM, Levy M. Tools for Practice #51. Available at: https://gomainpro.ca/wp-content/uploads/tools-for-practice/1433184684_updatedtfp51antidepressantsheadaches.pdf. Last accessed: July 21, 2021.

10. Linde M, Mulleners WM, Chronicle EP, et al. Cochrane Database Syst Rev . 2013 Jun 24; 2013(6):CD010610.

11. Rxfiles. Migraine: Agents for Prophylaxis. Available at: https://www.rxfiles.ca/RxFiles/uploads/documents/members/CHT-MIGRAINE.pdf. Last accessed: June 4, 2021

12. Sacco S, Bendtsen L, Ashina M, et al. J Headache Pain. 2019 Jan 16;20(1):6.

13. American Headache Society. Headache. 2019 Jan; 59(1):1-18.

Authors do not have any conflicts of interest to declare.

Les auteurs n’ont aucun conflit d’intérêts à déclarer.