Migraine headaches are among the most prevalent and disabling disorders. They affect more than 10% of Americans and more than 1 billion people worldwide. Migraine is a major source of disability, causing lost work and school days.
Medically, the challenges have been to understand the mechanism of these headaches, how to provide immediate relief, and how to prevent them from occurring. Migraine treatments include antidepressants, anticonvulsants, and hypertension medication like beta blockers. In recent years, the complex mechanics of migraine have been better pinpointed, and as a result, therapeutic options have begun to multiply.
A prime example is calcitonin gene-related peptide (CGRP). Elucidating its role in migraine has led to CGRP inhibitors, a drug class now used for acute migraine relief and chronic prevention. The members and attributes of this new drug class will be detailed here.
Drug name | Learn more | See SingleCare price |
---|---|---|
Nurtec | nurtec details | nurtec price |
Ubrelvy | ubrelvy details | ubrelvy price |
Qulipta | qulipta details | qulipta price |
Aimovig | aimovig details | aimovig price |
Ajovy | ajovy details | ajovy price |
Emgality | emgality details | emgality price |
Vyepti | vyepti details | vyepti price |
Calcitonin gene-related peptide inhibitors are a growing class of migraine treatment that came into use within the past few years. The CGRP blocker group includes both injectable and oral medications. Certain members of the class are indicated for acute treatment of episodic migraine headaches, and other members are approved for prevention of migraine attacks. A CGRP receptor antagonist may be chosen when alternative migraine treatments like triptans or botox are contraindicated or ineffective.
Prescription prophylactic medication is often recommended by a healthcare professional when someone is experiencing more than four migraine attacks per month or having particularly severe, prolonged, or disabling events. Preventive treatment is also indicated for chronic migraine, a condition defined as having 15 or more headache days per month for at least three months, with at least eight meeting migraine criteria.
The pathophysiology of migraine is understood to develop from a cascade of events within the nervous system and vasculature (blood vessels) of the brain, with CGRP being one player in a large cast. Initial depolarization of central nervous system neurons (nerve cells) spreads and triggers trigeminal nerve fibers, resulting in pain. The trigeminal nerve network releases CGRP, among other proteins that mediate inflammation and vascular tone. CGRP is active in pain signal transmission, vasodilator effects (blood vessel dilation), and brain inflammation, all of which amplify the headache pain.
Blocking CGRP can interrupt the sequence of migraine mechanisms and thereby provide relief from an attack or prevention when used regularly. Anti-CGRP agents work by either binding to CGRP itself or to the CGRP receptor site. The drugs themselves come in two forms, small molecules called gepants (Nurtec, Ubrelvy, and Qulipta) and large molecule monoclonal antibodies (Aimovig, Ajovy, Emgality, and Vyepti). Both forms disrupt CGRP action by preventing it from binding to and activating its receptor, and therefore, the migraine chain reaction is thwarted.
Acute migraine headache
Migraine headache prophylaxis
Episodic cluster headache
RELATED: Types of headaches
The small molecule members of the CGRP inhibitor family, termed gepants, are taken as an oral pill. Nurtec and Ubrelvy have both proven effective in increasing the chance of being pain-free within two hours of episodic migraine onset, compared to placebo (inactive pill used for comparison). Taken as a 50 or 100 mg single, swallowed tablet at migraine onset and repeated once if needed after at least two hours, Ubrelvy blocks the CGRP receptor. Nurtec acts similarly but is taken as a one-time 75 mg orally dissolvable tablet (ODT) at migraine onset.
Nurtec ODT can also be taken every other day for migraine prophylaxis, making it the only CGRP antagonist with Food and Drug Administration approval for both acute treatment of migraine and prevention of migraine.
Qulipta is a gepant with an FDA indication for migraine prophylaxis only. Prescribed as a 10 mg, 30 mg, or 60 mg daily dose, Qulipta has shown efficacy in reducing monthly migraine days at all doses.
The monoclonal antibody (mAb) subtypes of CGRP antagonists are all injectable medications aimed at curtailing the frequency of migraines among those suffering frequent recurrences or having chronic migraine.
A monthly subcutaneous (under the skin) injection of 140 mg of Aimovig has been shown to increase the chance of cutting migraine frequency down at least 50% and did so for more than a year in one extended study. In comparison, Ajovy can also outperform placebo in achieving a reduction in migraine days and does so with either a 225 mg monthly injection or 675 mg injection every three months.
The efficacy of Emgality extends to cluster headaches, in addition to its effectiveness in treatment of migraine. Emgality can be given as a single 300 mg injection to relieve an acute cluster headache episode and repeated monthly if needed to stop the episode. However, to prevent migraine effectively, it is given as a 240 mg loading dose the first month followed by 120 mg monthly injections.
Men are eligible to take anti-CGRP agents, but like everyone, they must review their other health problems with their prescribing provider beforehand to see if any contraindication or cautionary notes are present.
Women have a higher incidence of migraines than men. Fortunately, CGRP inhibitors are an option for women without contraindications.
A paucity of clinical trial data in pregnancy creates cause for concern when considering CGRP inhibitor use during pregnancy and breastfeeding, and some members of the class, such as Ubrelvy, Nurtec, and Qulipta, have shown possible harm in animal reproductive studies. In general, caution and a discussion of risks and benefits of using CGRP inhibitors in pregnancy are advisable.
CGRP inhibitors are not approved for use in children.
Seniors can take CGRP inhibitors, but similar to other patient demographic groups, this drug class is typically not the first choice for them. Theoretical concerns have been raised regarding blood pressure effects or cardiovascular risk, given the vasodilator effect of CGRP. Migraine therapeutics with a longer track record of use are often tried first.
None of the CGRP inhibitors currently have black box warning labels from the FDA.
There are no current recalls of CGRP antagonists, but the FDA’s database can be searched for updates.
CGRP blockers are contraindicated if an individual has a history of a hypersensitivity allergic reaction to the drug or another member of the drug class. Nurtec, Ubrelvy, and Qulipta should also be avoided by migraine patients with advanced liver disease. In addition, Ubrelvy and Qulipta are best avoided by individuals with advanced renal (kidney) disease.
The Drug Enforcement Administration (DEA) does not list CGRP inhibitors among their controlled substances.
The following are possible adverse effects across the CGRP inhibitor drug class. Ask your healthcare provider or pharmacist for a complete list of side effects of your particular medication.
Hypersensitivity allergic reactions
Urticaria (hives), rash, or flushing
Injection site reactions
Nausea, constipation, or abdominal pain
Fatigue
Weight loss
Elevated liver enzyme blood tests
Shortness of breath
Muscle spasm
A monthly supply of CGRP inhibitor therapy commonly costs about $800. Qulipta can cost more than $1,000 for 30 days of medication. The daunting prices do not have to be the end of your hopes for using this class of drug. Speak to your pharmacist and show your SingleCare discount card to see if a lower price is available.
Chad Shaffer, MD, earned his medical doctorate from Penn State University and completed a combined Internal Medicine and Pediatrics residency at the University of Pittsburgh Medical Center and Children’s Hospital of Pittsburgh. He is board certified by the American Board of Internal Medicine and the American Board of Pediatrics. He has provided full-service primary care to all ages for over 15 years, building a practice from start up to over 3,000 patients. His passion is educating patients on their health and treatment, so they can make well-informed decisions.
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