CGRP Antagonists

CGRP (calcitonin gene-related peptide) is a naturally neuropeptide protein involved in:

• Pain transmission

• Sensitization of migraine pathways

• Migraine attack generation

• Vasodilation

During migraine attacks, CGRP levels increase and contribute to headache pain and associated symptoms.

CGRP antagonists work by:

• Blocking CGRP itself, or

• Blocking the CGRP receptor

This reduces activation of migraine pathways and lowers the likelihood that a migraine attack will occur.

• They are preventive, not acute treatments

• They are migraine-specific, unlike many older preventives

• They do not suppress the immune system

They may be considered if you:

• Have episodic or chronic migraine

• Have frequent or disabling attacks

• Have not responded to or tolerated oral preventive medications

• Prefer a non-daily preventive option

CGRP antagonists are divided into two broad classes:

• CGRP monoclonal antibodies (monthly or quarterly injectable medications)

• Gepants (daily oral medications)

CGRP Monoclonal Antibodies

There are several CGRP monoclonal antibodies available. They differ mainly in how they are given.

Erenumab (Amovig ®)

• Blocks the CGRP receptor

• Self-administered injection

• Given once monthly

Eptinezumab (Vyepti ®)

• Targets CGRP

• Given by intravenous infusion

• Administered every 3 months

Fremanezumab (Ajovy ®)

• Targets CGRP

• Self-administered injection

• Given monthly or quarterly

Galcanezumab (Emgality ®)

• Targets CGRP

• Self-administered injection

• Given monthly

• Also approved for episodic cluster headache

Gepants

Atogepant (Qulipta ®) - prevention

• Taken once daily for migraine prevention

• Used to reduce migraine frequency

• Not used to treat acute attacks

Rimegepant (Nurtec ®) - acute use

• Taken once daily per attack

• Orally dissolving tablet

Ubrogepant (Ubrelvy ®) - acute use

• Taken at the start of a migraine attack

• A second dose may be taken 2 hours later if needed

CGRP Monoclonal Antibodies

• CGRP monoclonal antibodies are given either as subcutaneous injections (think of an autoinjector), or a short intravenous infusion

• Injections are typically either once per month or every 3 months

• These medications are not taken daily, which many patients find convenient.

Gepants

• Atogepant (Qulipta ®) is taken as a daily pill

• It has a short half-life

• Some people notice improvement within weeks

• Some CGRP antibodies have shown benefit in hours

• For others, benefit builds gradually

• A fair trial usually requires 3-6 months

• Full benefit may take 12 months

• Improvement may begin within days to weeks weeks

• A meaningful trial requires 8–12 weeks

CGRP monoclonal antibodies are generally well tolerated.

Possible side effects include:

• Injection-site reactions (redness, soreness)

• Constipation

• Muscle or joint aches (uncommon)

• Fatigue (uncommon)

• Urinary tract infections or nasopharyngitis (rare)

Serious side effects are rare.

Gepants are generally well tolerated.

Possible side effects include:

• Constipation

• Weight-loss

• Fatigue

Serious side effects are rare.

No.
These medications:

• Do not suppress the immune system

• Do not increase infection risk

• Are not considered immunosuppressive therapies

CGRP monoclonal antibodies are not recommended during pregnancy due to limited safety data.

If pregnancy is planned:

• These medications should be stopped at least 6 months before pregnancy

This allows time for the medication to fully clear from the body.

If you are pregnant or planning pregnancy, we will help you find alternative migraine strategies.

Gepants are not recommended during pregnancy due to limited safety data.

If pregnancy is planned:

• These medications should be stopped at least 1 week before pregnancy

This allows time for the medication to fully clear from the body.

If you are pregnant or planning pregnancy, we will help you find alternative migraine strategies.

Data on breastfeeding are limited but growing, and expert consensus is that CGRP monoclonal antibodies' expression in breast-milk is low, the amount of drug an infant may consume and ultimately absorb is trivial. Decisions are individualized based on:

• Migraine severity

• Available alternatives

• Patient preferences

We help guide these discussions using the best available evidence.

Data on gepant use and breastfeeding are limited but growing. Small case series suggest the amount of gepants in breastmilk is small.

We help guide the discussion around gepant-use during breastfeeding and lactation to help you make an informed decision.

In Ontario, coverage for CGRP monoclonal antibodies and atogepant (Qulipta ®) often requires:

• A diagnosis of episodic or chronic migraine

• Documentation of migraine frequency

• Trials of at least two oral preventive medications at therapeutic doses (usually for ~3 months each, depending on insurer)

We assist with:

• Insurance forms

• Prior authorization

From a medical perspective, CGRP monoclonal antibodies and gepants can be used:

• Alone

• Alongside other oral preventive medications

• Concurrently with Botox ® for chronic migraine, although insurers will typically not cover both

Insurance plans may restrict coverage of combination advanced therapies.

From a medical perspective, it is safe to combine CGRP monoclonal antibodies and gepants although the combination may increase the risk of constipation.

Insurance plans may restrict coverage of combining a preventive gepant - like atogepant (Qulipta ®) and CGRP monoclonal antibodies..

If CGRP monoclonal antibodies or gepants are effective:

• Treatment is continued

• There is no monitoring required

• Many patients can transition prescription renewal to their family physician

• Treatment may be discontinued 1-2 years later to revaluate whether it needs to be continued