Chronic migraine headaches can be debilitating, impacting a person’s quality of life and daily functioning. Fortunately, advancements in medical science have led to the development of CGRP (calcitonin gene-related peptide) antagonist drugs, a novel class of medications specifically designed for the management of chronic migraines. In this blog, we will delve into the mechanism of action of CGRP antagonist drugs, discuss their administration, efficacy, side effects, and contraindications, and explore how they can be combined with Botox for certain patients. Additionally, we will provide insights into how Dr. Krishna can assist patients with chronic migraines.
Understanding CGRP Antagonist Drugs:
CGRP antagonist drugs work by blocking the activity of calcitonin gene-related peptide, a neurotransmitter involved in pain transmission and inflammation. By inhibiting CGRP, these medications aim to reduce the frequency, severity, and duration of migraine attacks.
Administration and Dosage:
CGRP antagonist drugs are typically administered via subcutaneous injections or, in some cases, through intravenous infusions. The frequency of administration depends on the specific medication prescribed and can range from monthly to quarterly doses. It is essential to follow the prescribed dosage instructions provided by your healthcare professional.
Mechanism of Action:
CGRP is a neuropeptide that plays a key role in the pathophysiology of migraine, as it is involved in the transmission of pain signals, the dilation of blood vessels, and the inflammation of the meninges. CGRP levels are elevated during migraine attacks and correlate with the intensity of pain. CGRP antagonist drugs work by binding to CGRP receptors and preventing the interaction between CGRP and its receptors. This blockade reduces the activation of pain pathways and inflammatory processes associated with migraines, ultimately leading to a decrease in migraine frequency and intensity.
Efficacy and Benefits:
Clinical trials have shown that CGRP antagonist drugs offer significant benefits for individuals with chronic migraines. Research studies, such as the STRIVE trial (Dodick et al., 2019) and the ARISE trial (Goadsby et al., 2019), have demonstrated that CGRP antagonists can effectively reduce the frequency of monthly migraine attacks and provide relief from associated symptoms, such as nausea and sensitivity to light and sound. CGRP antagonists have been shown to be effective in reducing the number of monthly migraine days by 50% or more in about 50% to 60% of patients with chronic migraine.
CGRP antagonists currently available in the US:
There are five CGRP antagonists approved by the FDA as of November 2022:
- Atogepant: a pill that can be taken once daily to prevent migraine attacks. It blocks the sites where CGRP attaches to its receptor.
- Erenumab: an injection that can be given once monthly or quarterly to prevent migraine attacks. It binds to the CGRP receptor and prevents CGRP from causing pain.
- Eptinezumab: an intravenous infusion that can be given every three months to prevent migraine attacks. It also binds to CGRP and inhibits its action.
- Fremanezumab: an injection that can be given once monthly or quarterly to prevent migraine attacks. It binds to CGRP and prevents it from causing pain.
- Galcanezumab: an injection that can be given once monthly to prevent migraine attacks. It also binds to CGRP and inhibits its action.
CGRP antagonists currently available in the UK:
In the UK, there are currently three CGRP antagonist drugs approved for the management of chronic migraines: Erenumab (Aimovig), Fremanezumab (Ajovy), and Galcanezumab (Emgality). These medications are administered via subcutaneous injections. Erenumab is typically prescribed as a monthly dose of 70 mg or 140 mg, with some patients benefiting from a quarterly 210 mg dose. Fremanezumab is available in two dosing options: a monthly 225 mg dose or a quarterly 675 mg dose. Galcanezumab is also offered in two dosages: a monthly 120 mg dose or a quarterly 240 mg dose. The specific medication and dosage prescribed may vary depending on individual patient factors and response to treatment. It is important to consult a healthcare professional to determine the most appropriate CGRP antagonist and dosage for your specific needs.
- Erenumab (Aimovig):
- Dosage: Monthly doses of 70 mg or 140 mg, with some patients receiving a quarterly 210 mg dose.
- Mode of administration: Subcutaneous injection.
- Efficacy: In clinical trials, Erenumab has shown efficacy in reducing the frequency of monthly migraine attacks and improving patient-reported outcomes.
- Side effects: The most common side effects reported include injection site reactions, constipation, and muscle cramps.
- Galcanezumab (Emgality):
- Dosage: Monthly doses of 120 mg or quarterly doses of 240 mg.
- Mode of administration: Subcutaneous injection.
- Efficacy: Clinical trials have demonstrated the efficacy of Galcanezumab in reducing monthly migraine days and improving patient-reported outcomes.
- Side effects: The most common side effects reported include injection site reactions and headache.
- Fremanezumab (Ajovy):
- Dosage: Monthly doses of 225 mg or quarterly doses of 675 mg.
- Mode of administration: Subcutaneous injection.
- Efficacy: Clinical trials have shown that Fremanezumab significantly reduces the frequency of monthly migraine attacks and improves patient-reported outcomes.
- Side effects: The most common side effects reported include injection site reactions and hypersensitivity reactions.
NICE recommendations for the use of CGRP antagonists:
The National Institute for Health and Care Excellence (NICE) provides guidelines for the use of CGRP antagonists in the UK. According to NICE, CGRP antagonists should be considered for the preventive treatment of chronic migraines in adults when at least three prior preventive treatments have been tried and failed, or when the patient has contraindications, intolerance, or significant adverse effects to these treatments. NICE also recommends that CGRP antagonists should only be prescribed by headache specialists or healthcare professionals with expertise in managing migraine. Chronic migraine is defined as experiencing a headache on 15 or more days per month, of which at least 8 days are migrainous, for at least 3 months.
Comparison of CGRP antagonists with other migraine drugs/treatments:
HER-MES trial: This trial compared Erenumab, a CGRP receptor antagonist, with topiramate, a standard preventive therapy, in patients with episodic migraine. The results showed that Erenumab was more effective and better tolerated than topiramate, with a higher percentage of patients achieving at least 50% reduction in monthly migraine days and fewer adverse events.
Head-to-Head Study Comparing Once-Monthly Emgality® (galcanezumab) with Nurtec® ODT (Rimegepant) for the Prevention of Episodic Migraine: This is an ongoing phase 4 trial that will compare galcanezumab, a CGRP monoclonal antibody, with rimegepant, an oral CGRP receptor antagonist, in patients with episodic migraine. The primary endpoint is the percentage of patients achieving at least 50% reduction in monthly migraine days across a 3-month treatment period. The trial is expected to enroll 700 patients and complete in 2023.
Anti-CGRP monoclonal antibodies for migraine prevention: A systematic review and likelihood to help or harm analysis: This is a systematic review that compared the benefit-risk ratios of anti-CGRP monoclonal antibodies (Erenumab, Fremanezumab, Galcanezumab, and Eptinezumab) with established treatments (topiramate, propranolol, and onabotulinumtoxinA) for episodic and chronic migraine. The results showed that anti-CGRP monoclonal antibodies had a more favourable benefit-risk ratio than established treatments, with a higher likelihood to help versus harm values. However, the authors noted that head-to-head studies are needed to confirm these results. (Cephalalgia 2021 Jun;41(7):851-864)
While CGRP antagonist drugs are generally well-tolerated, like any medication, they may have potential side effects. Common side effects reported include injection site reactions (such as pain, redness, or swelling), constipation, fatigue, and muscle stiffness. It is essential to discuss any concerns or side effects with your healthcare professional to determine the best course of action. They have no known drug interactions and do not cause medication-overuse headaches.
CGRP antagonist drugs are generally safe for most individuals with chronic migraines. However, it is crucial to inform your healthcare professional about your medical history and any existing conditions, as certain factors may contraindicate their use. Contraindications may include pregnancy, breastfeeding, liver or kidney disease, and severe allergies to the medication.
Combining CGRP Antagonists with Botox:
In some cases, healthcare professionals may recommend combining CGRP antagonist drugs with Botox injections for optimal management of chronic migraines. Botox injections work by blocking the release of various neurotransmitters, including CGRP, in pain pathways. Combining both treatment modalities can potentially enhance the effectiveness of migraine management, offering patients a comprehensive approach to relief.
How Dr Krishna Can Help Patients with Chronic Migraines:
Dr Krishna, a well-known Pain Specialist, is dedicated to providing personalized care and support for individuals with chronic migraines. With extensive experience in the field, Dr Krishna employs evidence-based treatment approaches, including the use of CGRP antagonist drugs, to alleviate migraine symptoms and improve the overall well-being of patients.
CGRP antagonist drugs have emerged as a promising treatment option for individuals with chronic migraines. With their mechanism of action targeting CGRP, these medications offer effective relief by reducing migraine frequency and severity. While considering the potential side effects and contraindications, CGRP antagonists, can provide comprehensive relief and improve the lives of those living with chronic migraines.
- Dodick DW, Silberstein SD, Bigal ME, et al. Effect of fremanezumab compared with placebo for prevention of episodic migraine: a randomized clinical trial. JAMA. 2019;321(23): 2291-2301.
- Goadsby PJ, Reuter U, Hallström Y, et al. A controlled trial of erenumab for episodic migraine. N Engl J Med. 2017;377(22):2123-2132.