How Ajovy Works and its Effect on Blood Pressure
Ajovy (fremanezumab) is a monoclonal antibody used for the preventive treatment of migraine. It works by targeting the calcitonin gene-related peptide (CGRP). CGRP is a naturally occurring peptide that plays a crucial role in migraine attacks, but also has a powerful vasodilatory effect—meaning it helps relax blood vessels and lower blood pressure. By blocking CGRP, Ajovy and other CGRP antagonists prevent vasodilation, which in some cases can lead to an increase in blood pressure.
Clinical Trials vs. Real-World Experience
There is a notable difference between what was observed in initial clinical trials and what has been reported in post-marketing surveillance.
Clinical trials are designed with strict inclusion criteria and often exclude patients with unstable or poorly controlled cardiovascular conditions. In the HALO Phase 3 clinical trials for Ajovy, fewer than 1% of patients experienced hypertension, which was a similar rate to those on placebo. This gave a favorable impression of its cardiovascular safety profile during the initial approval process.
However, in the real world, the patient population is much broader and includes individuals with pre-existing risk factors for high blood pressure. Since its approval, post-marketing reports have documented cases of new-onset hypertension and the worsening of pre-existing hypertension following the use of Ajovy. Some of these cases required medical intervention, including starting blood pressure medication or even hospitalization.
Key Considerations Regarding Hypertension Risk
- Class Effect: The risk of hypertension is not unique to Ajovy. It is considered a class effect for CGRP antagonists, as similar post-marketing reports have been associated with Aimovig (erenumab) and Emgality (galcanezumab).
- Risk Factors: Patients with pre-existing hypertension or other cardiovascular risk factors may be more susceptible to this side effect.
- Onset of Hypertension: The rise in blood pressure can occur at any point during treatment, but in many reported cases, it was noted shortly after starting therapy, sometimes within seven days.
- Monitoring is Crucial: Due to the potential risk, healthcare providers should monitor patients on Ajovy for new or worsening hypertension.
Comparison of CGRP Monoclonal Antibodies and Hypertension
| Feature | Ajovy (Fremanezumab) | Aimovig (Erenumab) | Emgality (Galcanezumab) |
|---|---|---|---|
| Mechanism | Targets and blocks CGRP ligand | Targets and blocks CGRP receptor | Targets and blocks CGRP ligand |
| Hypertension in Clinical Trials | <1% incidence, similar to placebo | Not clinically significant, though some dose-related trends seen | <1% incidence, similar to placebo |
| Hypertension in Post-marketing | Documented cases of new-onset and worsening hypertension | Specific reports led to a label update regarding hypertension risk | Documented cases of new-onset and worsening hypertension |
| Timing of Onset (Post-marketing) | Most frequently reported within 7 days of initiation | Can occur anytime, but often within 7 days of initiation | Can occur anytime, but often within 7 days of initiation |
| Patient Action | Inform healthcare provider if blood pressure increases | Inform healthcare provider if blood pressure increases | Inform healthcare provider if blood pressure increases |
Monitoring and Management of Blood Pressure
For patients taking Ajovy, monitoring blood pressure is an important step to ensure overall cardiovascular health. Here is what patients and healthcare providers should consider:
For Patients
- Regular Blood Pressure Checks: Especially if you have a history of high blood pressure or other cardiovascular risk factors, your doctor may ask you to check your blood pressure regularly at home.
- Know the Symptoms: While increases in blood pressure can be unnoticeable, symptoms of severely high blood pressure can include blurred vision, dizziness, headache, or a pounding in the ears.
- Contact Your Doctor: If you notice an increase in your blood pressure or experience any concerning symptoms, contact your healthcare provider immediately.
For Healthcare Providers
- Baseline Assessment: A thorough cardiovascular assessment should be conducted before starting Ajovy, especially for patients with a history of hypertension.
- Ongoing Monitoring: Regular blood pressure monitoring is recommended during treatment.
- Manage Changes: If new-onset or worsening hypertension occurs, a careful evaluation is needed to determine if an alternative cause exists. In many post-marketing cases, discontinuation of Ajovy was warranted when blood pressure became inadequately controlled. Depending on the severity, patients may need new or adjusted antihypertensive medication.
Conclusion
In summary, while Ajovy (fremanezumab) is an effective preventive treatment for migraine, it carries a post-marketing risk of causing or worsening high blood pressure, a known effect of CGRP-antagonist medications. This risk was not prominently observed in initial controlled clinical trials, which underscores the importance of real-world surveillance. Patients, particularly those with pre-existing cardiovascular conditions, should be vigilant and communicate any changes in blood pressure with their healthcare provider. Regular monitoring and proactive management are crucial for ensuring the safety and effectiveness of Ajovy therapy. American Heart Association provides extensive resources on managing high blood pressure.
The Role of CGRP in Blood Pressure
Calcitonin gene-related peptide (CGRP) is a potent vasodilator, meaning it helps to relax and widen blood vessels. It plays a protective role in the cardiovascular system, especially during stressful events like myocardial infarction or stroke, by increasing blood flow. By blocking CGRP or its receptor to prevent migraines, Ajovy and other CGRP antagonists may inadvertently interfere with this protective mechanism, potentially leading to increased blood pressure. This is particularly relevant for individuals with cardiovascular risk factors, for whom CGRP's protective effect is most critical.
