Eptinezumab

Introduction to Eptinezumab

Eptinezumab (brand name Vyepti) is a humanized monoclonal antibody that targets calcitonin gene-related peptide (CGRP). It was developed by Lundbeck (formerly Alder BioPharmaceuticals) and received FDA approval in 2020 for the preventive treatment of migraine in adults. While primarily used in adult neurology, its mechanism and potential applications are important for pediatricians to understand, especially when managing pediatric patients with severe or refractory migraines.

Mechanism of Action

Eptinezumab works through the following mechanisms:

  • Selectively binds to both α and β forms of the calcitonin gene-related peptide (CGRP)
  • Prevents CGRP from binding to its receptors
  • Inhibits CGRP-mediated vasodilation, neurogenic inflammation, and pain signal transmission

By targeting CGRP, a neuropeptide involved in pain signaling and neurogenic inflammation, eptinezumab aims to prevent the onset of migraine attacks and reduce their frequency, severity, and duration.

Indications

Eptinezumab is FDA-approved for:

  • Preventive treatment of migraine in adults

It is indicated for both episodic and chronic migraine prevention in adult patients. Eptinezumab may be considered for patients who:

  • Have 4 or more migraine days per month
  • Experience significant disability due to migraines
  • Have not responded adequately to or cannot tolerate other preventive treatments

While not approved for pediatric use, there is growing interest in its potential application for adolescents with severe or refractory migraines.

Dosage and Administration

The recommended dosage for adults is:

  • 100 mg administered by intravenous infusion every 3 months
  • Some patients may benefit from a dosage of 300 mg every 3 months

Administration details:

  • Administered as an intravenous infusion over approximately 30 minutes
  • Must be diluted prior to administration
  • Should be administered by a healthcare professional
  • No loading dose is required

Note: Dosing for pediatric patients, if used off-label, would need to be carefully adjusted based on weight and monitored closely.

Clinical Efficacy

Clinical trials have demonstrated the efficacy of eptinezumab in adult populations:

  • In episodic migraine:
    • Reduced monthly migraine days by 3.9 days (300 mg) and 3.2 days (100 mg) compared to 2.0 days for placebo
    • About 50% of patients achieved a ≥50% reduction in monthly migraine days
  • In chronic migraine:
    • Reduced monthly migraine days by 8.2 days (300 mg) and 7.7 days (100 mg) compared to 5.6 days for placebo
    • About 60% of patients achieved a ≥50% reduction in monthly migraine days
  • Onset of preventive benefit was observed as early as day 1 after infusion

Long-term studies are ongoing to assess the durability of these effects and long-term safety profile.

Side Effects

Common side effects observed in clinical trials include:

  • Nasopharyngitis
  • Hypersensitivity reactions
  • Fatigue
  • Nausea
  • Urinary tract infection

Serious adverse events to be aware of:

  • Hypersensitivity reactions, including anaphylaxis (rare)
  • Potential for immunogenicity (development of anti-drug antibodies)

Compared to other CGRP antagonists, eptinezumab has shown a relatively favorable safety profile, with a low incidence of injection site reactions due to its intravenous administration.

Pediatric Considerations

While eptinezumab is not currently approved for pediatric use, pediatricians should be aware of the following:

  • Safety and efficacy in pediatric populations have not been established
  • Clinical trials are ongoing to evaluate its use in adolescents with chronic migraine
  • Off-label use in pediatric patients should be approached with caution and only after careful consideration of risks and benefits
  • Potential long-term effects on the developing nervous system are not fully understood
  • The intravenous administration might be challenging in some pediatric patients
  • Close monitoring for side effects, particularly hypersensitivity reactions, is crucial if used in pediatric patients

Pediatricians should stay informed about emerging data and guidelines regarding the use of CGRP antagonists like eptinezumab in children and adolescents with migraine.



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