CGRP Monoclonal Antibodies Not More Effective Than Topiramate or Botox for Treating Migraine

A new study did not provide evidence that the newer calcitonin gene-related peptide (CGRP) monoclonal antibodies are more clinically effective at treating chronic migraine than topiramate or Botox.¹

“Within the current care pathway, it is unlikely that CGRP [monoclonal antibodies] will be recommended ahead of topiramate without a very substantial reduction on price,” investigators wrote, led by Hema Mistry, PhD, from the Warwick Clinical Trials Unit at Warwick Medical School, University of Warwick, in the UK.

In 2020, CGRP monoclonal antibodies have been established as the treatment given to patients with chronic migraine who do not respond to other medications.² These antibodies are more expensive than cheaper, well-established oral medications to treat migraine. However, does the effectiveness make the cost worth it?

Limited data was available on the effectiveness of CGRP monoclonal antibodies compared with other migraine medications.¹ Investigators conducted a systematic review to compare the clinical and cost-effectiveness of prophylactic drug treatments for people with chronic migraine. The hope was that the findings would provide evidence-backed recommendations for clinicians to best treat their patients.

The review included 11 randomized controlled trials testing the 6 drugs: topiramate, Botox, eptinezumab, erenumab, fremanezumab, and galcanezumab. The studies (7352 participants total; ≥ 100 participants per arm) had evidence on clinical effectiveness, cost-effectiveness, and the comparative incidence of adverse events of prophylactic medications for chronic migraine.

Analyses included data on headache days, migraine days, headache-related quality of life, migraine-specific quality of life, and headache impact test 6. The team did not include any trials with commonly used drugs, such as amitriptyline, candesartan, flunarizine or propranolol, due to insufficient quality.

Investigators developed an economic model comparing the cost-effectiveness of prophylactic drugs for chronic migraine using an adult population from a National Health Service and personal social services. The model was based on an analysis with a 2-year time horizon; at baseline, participants were aged ≥ 30 years.

CGRP monoclonal antibodies reduced headache or migraine days by 2.0 to 2.5 days per month. As for Botox and topiramate, they reduced headaches by less than 1.5 days per month.

The meta-analysis showed eptinezumab 300 mg performed the best at reducing monthly headaches, reducing them by 2.46 (95% credible interval [Crl], 3.24 to 1.67) days. Moreover, the most effective medication in reducing monthly migraine days was fremanezumab monthly which reduced them by 2.76 (95% CrI −3.36 to −2.15) days.

The CGRP monoclonal antibodies appeared to be the best choice for headache or migraine days and headache-related quality of life. Topiramate, which reduced headache days by < 1.5 fewer headache days per month, was the least effective when compared to Botox (reduced migraine headache by 1.87 days; 95% CrI, -1.55 to -1.18 days per month) or CGRP monoclonal antibodies.

The adverse events review included 40 randomized controlled trials with 25,891 participants. Three other drugs, amitriptyline, atogepant, and rimegepant, were included in this analysis.

Adverse events were common, but there were no serious adverse events linked to the medication. Participants on CGRP monoclonal antibodies reported injection site issues, and participants on topiramate or amitriptyline had nervous system or gastrointestinal issues.

Moreover, the cost-effectiveness review included 16 studies. The team discovered the newer, injected drugs were more expensive drugs were more expensive than the oral drugs but were cost-effective.

The economic model demonstrated topiramate was the least expensive option but had the fewest quality-adjusted life-year gains. Moreover, eptinezumab 300 mg was more expensive but resulted in the most quality-adjusted life-year gains. The analysis found topiramate was the most cost-effective medication if the patient is willing to pay ≥ £ 50,000 per quality-adjusted life-year.

The team identified 3 areas for future research on chronic migraine treatment, including CGRP monoclonal antibodies and Botox compared with CGRP monoclonal antibodies alone; candesartan vs placebo; and flunarizine vs placebo.

Investigators said the study was limited by only including 1 oral drug since topiramate was the only one with sufficient data.

“It is disappointing that we did not find a sufficient quality evidence base to support the use of drugs, such as amitriptyline, candesartan, flunarizine and propranolol that are recommended by the National Institute for Health and Care Excellence (NICE) and/or Scottish Intercollegiate Guidelines Network (SIGN),” investigators wrote. “Our consensus meeting identified the need for trials comparing candesartan and flunarizine with placebo as the top priorities for placebo-controlled trials.”

References

1. ^{Mistry H, Naghdi S, Brown A, et al. Preventive drug treatments for adults with chronic migraine: a systematic review with economic modelling. Health Technol Assess. 2024;28(63):1-329. doi:10.3310/AYWA5297}
2. ^{Forbes RB, McCarron M, Cardwell CR. Efficacy and Contextual (Placebo) Effects of CGRP Antibodies for Migraine: Systematic Review and Meta-analysis. Headache. 2020;60(8):1542-1557. doi:10.1111/head.13907}