CGRP Monoclonal Antibodies

CGRP monoclonal antibodies bind CGRP or its receptor and prevent migraine by blocking trigeminovascular signalling. They are the first migraine preventives designed for the disorder and are given by injection or infusion at long intervals.

Classification. Anti-receptor antibody (erenumab); anti-ligand antibodies (fremanezumab, galcanezumab, eptinezumab).

Pharmacokinetics. Half life about 4 weeks. Cleared by proteolysis, with no liver or kidney clearance and no CYP interactions.

• Erenumab 70 mg or 140 mg subcutaneously every 4 weeks.
• Fremanezumab 225 mg subcutaneously monthly or 675 mg every 3 months.
• Galcanezumab 240 mg subcutaneously as a loading dose, then 120 mg monthly; cluster headache 300 mg at the start of a bout, then monthly.
• Eptinezumab 100 mg or 300 mg intravenously every 12 weeks.

Differences. Erenumab more often causes constipation and rises in blood pressure. The three ligand antibodies share a similar profile.

• Indication: episodic migraine with 4 or more migraine days a month, or chronic migraine, after failure of at least 2 or 3 other preventives.
• Response: judge at 12 weeks; a 50 percent fall in monthly migraine days is a response. Stop if there is none.
• Duration: a break after 6 to 12 months is considered.
• Combination: not with botulinum toxin unless specialist direction.

Selection. Preferred where other preventives are contraindicated or cause intolerable effects; drug costs limit access in East Africa.

Contraindications. Hypersensitivity. Caution in cardiovascular and cerebrovascular disease, Raynaud phenomenon, and severe constipation.

Adverse effects. Injection site reactions, constipation (can be severe with obstruction), hypertension, Raynaud phenomenon, hypersensitivity, alopecia and pruritus (erenumab).

Interactions. None of note.

Special groups.

• Pregnancy: avoid; the antibodies cross the placenta in the second and third trimesters. Stop about 5 months before conception.
• Breastfeeding: limited data.
• Children: not licensed.
• Older adults: limited data over 65.
• Kidney and liver impairment: no adjustment.

Monitoring. Blood pressure at baseline and after starting; bowel habit; migraine diary at 12 weeks.

Referral and escalation. Severe constipation or abdominal pain, new hypertension, ischaemic symptoms, or no response after 12 weeks.