Tools for Practice


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


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

BOTTOM LINE
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
  • 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.

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Author(s):

  • Clark Svrcek MD CCFP
  • Joey Ton PharmD
  • Sandra Trkulja BScPharm PharmD
  • Trudy Huyghebaert PharmD

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.