A new network meta-analysis published in Frontiers in Pharmacology provides important insights into the relative efficacy and safety of monoclonal antibodies targeting calcitonin gene-related peptide (CGRP) for migraine prevention.
This comprehensive analysis compares four CGRP monoclonal antibodies – eptinezumab, erenumab, fremanezumab, and galcanezumab – and sheds light on which ones are most effective for reducing monthly migraine days and headache frequency.
Key Takeaways:
- The analysis included 18 randomized controlled trials with over 8,900 migraine patients. All four CGRP antibodies significantly reduced monthly migraine days versus placebo.
- Fremanezumab ranked highest for efficacy, resulting in the greatest reduction in monthly migraine days. Galcanezumab ranked second.
- Galcanezumab was associated with more treatment-emergent and serious adverse events compared to placebo. Fremanezumab ranked safest.
- For reducing migraine frequency by 50%, fremanezumab outperformed eptinezumab. For 75% response rates, fremanezumab again ranked highest.
- Head-to-head studies are still needed, but this analysis provides evidence that fremanezumab may offer advantages in efficacy, while galcanezumab may confer more side effects.
Source: Front. Pharmacol.
Treating Migraine with CGRP Antibodies
Migraine is a neurological disease that affects approximately 15% of the global population.
It is characterized by severe, recurring headaches and symptoms like nausea, vomiting, and sensitivity to light and sound.
Migraine is a leading cause of disability worldwide.
Despite available treatments like antidepressants, anti-seizure drugs, and botox injections, many migraine patients experience insufficient relief and side effects from medications.
This has driven interest in a new class of preventive therapies – monoclonal antibodies that target CGRP or its receptor.
CGRP is a neuropeptide involved in pain transmission and vasodilation.
Four CGRP monoclonal antibodies have been approved for migraine prevention:
- Eptinezumab (Vyepti)
- Erenumab (Aimovig)
- Fremanezumab (Ajovy)
- Galcanezumab (Emgality)
These antibodies work by blocking CGRP or its receptor, disrupting pathways involved in migraine.
Previous meta-analyses compared each one individually to placebo, but head-to-head comparisons were lacking.
This motivated the current network meta-analysis.
Overview of the Meta-Analysis: CGRP Antibodies to Prevent Migraines
The meta-analysis aimed to provide direct and indirect comparisons between the four CGRP antibodies for two efficacy outcomes – change in monthly migraine days and 50/75% response rates (proportion with halved/quartered headache days) – and two safety outcomes – treatment-emergent and serious adverse events.
The authors systematically searched literature databases to identify randomized controlled trials on CGRP antibodies in migraine patients.
18 trials met inclusion criteria, comprising over 8,900 patients.
13 trials were multi-country. The mean study follow-up was 12 weeks.
WinBUGS software was used to conduct Bayesian network meta-analyses, incorporating both direct and indirect comparisons between treatments.
The rankings of each CGRP antibody for efficacy and safety outcomes were estimated.
Efficacy Outcomes: Reductions in Migraine Burden
For the primary outcome of change in monthly migraine days, all four CGRP antibodies resulted in statistically significant reductions compared to placebo:
- Fremanezumab: 2.19 fewer migraine days per month
- Galcanezumab: 2.10 fewer days Erenumab: 1.61 fewer days
- Eptinezumab: 1.43 fewer days
Fremanezumab and galcanezumab provided the greatest reductions.
Though no significant differences occurred between antibodies, fremanezumab had the highest probability of ranking best for efficacy.
For 50% response rates (halving monthly migraine days), erenumab, fremanezumab, and galcanezumab outperformed placebo.
Fremanezumab also reduced 50% response rates significantly more than eptinezumab.
Similarly, for 75% response rates, eptinezumab, fremanezumab, and galcanezumab surpassed placebo. Fremanezumab again had the highest probability of ranking first.
Safety Outcomes: Adverse Events from CGRP ABs
Regarding treatment-related adverse events, galcanezumab was associated with significantly more events than placebo, primarily injection site reactions and infections.
Galcanezumab had the highest probability of ranking worst for safety.
For serious adverse events, only galcanezumab conferred significantly increased risk versus placebo. The events varied widely between studies.
In summary, while all CGRP antibodies effectively reduced migraine burden, fremanezumab appeared most efficacious.
However, galcanezumab was linked to greater adverse effects.
Expert Discussion: CGRP Antibodies for Migraine Prophylaxis
This comprehensive network meta-analysis provides valuable insights into the comparative effectiveness and safety of the four approved CGRP monoclonal antibodies for migraine prevention.
The results suggest that fremanezumab (Ajovy) may confer slightly greater reductions in monthly migraine days and higher response rates than the other three antibodies.
While head-to-head trials are still needed, this analysis provides preliminary evidence that fremanezumab could offer advantages in efficacy.
However, galcanezumab (Emgality) was associated with more treatment-related adverse events.
Although infrequent, serious adverse events were also significantly elevated with galcanezumab compared to placebo.
This indicates a less favorable safety profile.
There are some limitations. The trials had varying inclusion criteria, follow-up periods, and data reporting.
Publication bias cannot be excluded. Nonetheless, this network meta-analysis synthesizes the totality of evidence thus far.
The American Headache Society guidelines already recommend all four CGRP antibodies as preventive migraine treatments.
But they do not differentiate between them.
These findings suggest that neurologists may want to consider fremanezumab as a first-line option given its superior efficacy.
However, galcanezumab’s usage could be reserved for patients intolerant to other options, given its comparatively worse safety profile.
Of course, factors like patient preferences, insurance coverage, administration routes, and out-of-pocket costs may also affect medication choice.
Still, this meta-analysis provides valuable new information that can help guide clinical decision making.
As more real-world evidence emerges, we will gain further clarity around the risk-benefit profiles and optimal roles for each CGRP antibody in migraine management.
But for now, this comprehensive network meta-analysis points to important differences that neurologists and headache specialists should be aware of when selecting treatments.
References
- Study: Efficacy and safety of monoclonal antibody against calcitonin gene-related peptide or its receptor for migraine
- Authors: Xing Wang et al. (2021)
