What is the comparison between Emgality (galcanezumab) and Ubrelvy (ubrogepant) for migraine treatment?

Comparison of Emgality (Galcanezumab) vs. Ubrelvy (Ubrogepant) for Migraine Treatment

Emgality and Ubrelvy serve different purposes in migraine management - Emgality is for prevention while Ubrelvy is for acute treatment, making them complementary rather than competing treatments.

Key Differences

Indications

• Emgality (galcanezumab):

  • FDA-approved for preventive treatment of migraine in adults 1
  • Also indicated for treatment of episodic cluster headache in adults 1
  • Administered monthly as a subcutaneous injection

• Ubrelvy (ubrogepant):

  • FDA-approved only for acute treatment of migraine with or without aura in adults 2
  • Not indicated for preventive treatment 2
  • Taken orally as needed during migraine attacks

Mechanism of Action

Both medications target the calcitonin gene-related peptide (CGRP) pathway, but through different mechanisms:

• Emgality: Monoclonal antibody that binds to CGRP
• Ubrelvy: Small-molecule CGRP receptor antagonist (gepant)

Efficacy

Emgality (Prevention)

• Recommended as preventive therapy with a "weak for" recommendation by the VA/DoD guidelines 3
• Can reduce monthly migraine days by up to 50% 4
• Particularly effective for episodic cluster headache (recommended) but not recommended for chronic cluster headache 3

Ubrelvy (Acute Treatment)

• Recommended with a "weak for" recommendation for short-term treatment of migraine 3
• Clinical trials showed:
  • Pain freedom at 2 hours: 19.2% (50mg) and 21.2% (100mg) vs 11.8% with placebo 5
  • Freedom from most bothersome symptom at 2 hours: 38.6% (50mg) and 37.7% (100mg) vs 27.8% with placebo 5
  • Improved functional disability: 40.6% of patients reported normal function at 2 hours vs 32.0% with placebo 6

Safety Profile

Emgality

• Most common adverse events: injection site reactions
• Serious hypersensitivity reactions including dyspnea, urticaria, and rash have been reported 1
• Cases of anaphylaxis and angioedema reported in postmarketing setting 1

Ubrelvy

• Most common adverse events: nausea (2-4%), somnolence, and dry mouth 5
• No significant hepatotoxicity reported at therapeutic doses 7
• Lower adverse event rate at 50mg (9.4%) compared to placebo (12.8%) 5

Usage Limitations

• Emgality: Monthly injection, requires consistent use for effectiveness
• Ubrelvy: Limited to no more than 8 days per month to avoid medication overuse headache 8

Treatment Algorithm

When to Choose Emgality:

1. For patients with:

   • ≥4 migraine days per month, or
   • ≥2 migraine days with significant disability despite appropriate acute treatments 8
   • Episodic cluster headache 1

2. Dosing:

   • For migraine: 240mg loading dose (two 120mg injections), then 120mg monthly 1
   • For episodic cluster headache: 300mg (three 100mg injections) at onset of cluster period, then monthly until end of cluster period 1

When to Choose Ubrelvy:

1. For acute treatment of migraine attacks when:

   • First-line treatments (NSAIDs, aspirin-acetaminophen-caffeine) are ineffective 3
   • Triptans are contraindicated or not tolerated 8
   • Patient needs an alternative to triptans

2. Dosing:

   • 50mg or 100mg as a single dose
   • May take a second dose if needed
   • Maximum 200mg in 24 hours
   • Limit use to ≤8 days per month to prevent medication overuse headache 8

Practical Considerations

First-Line Treatment Approach

According to guidelines, treatment should follow this sequence:

1. Start with NSAIDs or aspirin-acetaminophen-caffeine for acute attacks 3
2. Use triptans as second-line for acute treatment 3
3. Consider gepants like Ubrelvy as alternative acute treatments 3
4. Consider preventive therapy with beta-blockers, tricyclics, or anticonvulsants for frequent migraines 3, 8
5. Consider Emgality for prevention when other preventives fail 3, 8

Combination Use

• These medications can be used complementarily - Emgality for prevention and Ubrelvy for breakthrough attacks
• This approach addresses both prevention and acute treatment needs

Conclusion

For patients with frequent, disabling migraines requiring both prevention and acute treatment, a combination approach may be optimal - using Emgality for monthly prevention and Ubrelvy for acute attacks when they occur. For patients with infrequent migraines, Ubrelvy alone may be sufficient as an acute treatment option.