Fremanezumab (AJOVY™) was the second mAb approved, followed pretty quickly by the third, galcanezumab (Emgality™). All 3 of these mAbs are administered once a month by a subcutaneous injection from an autoinjector. If a patient takes 3 fremanezumab injections in 1 day, they do not have to repeat that dose for 3 months. The upside of these 3 treatments is that the patient can self-administer the medication at home with few, if any, adverse events; the downside is they are expensive medications, costing about $600 per month .
Shortly thereafter, a fourth mAb, eptinezumab (VYEPTI™), was brought to market. Unlike the other 3 mAbs, it is administered as an intravenous infusion. The patient must come to an office or infusion center for a 30-minute intravenous infusion, which is not as convenient as treating themselves with an autoinjector at home. Eptinezumab is a strong medication that is often prescribed when other treatments are not effective. Each of the 4 mAbs has its own possible adverse events, but these are few and usually mild. The mAbs have a half-life of about 28 to 32 days; it takes 5 to 6 months after an injection for these mAbs to be metabolized by the reticuloendothelial system.
Gepants
The gepants are small molecule CGRP receptor blockers with much shorter half-lives than mAbs. They work by blocking the CGRP receptor so the CGRP ligand cannot dock there and cause vasodilation and increased pain transmission. Gepants have half-lives of 6 to 12 hours and can be used to treat a migraine acutely. Several drug companies studied the effects of taking a gepant every day or every other day, showing it can also be used as a migraine preventive medication. Ubrogepant (Ubrelvy®) was the first gepant to receive approval from the US Food and Drug Administration (FDA), but it was authorized only for acute care. Rimegepant (Nurtec®) was the second gepant approved , initially for acute treatment and later becoming the first gepant approved for migraine prevention . The same tablet can be used for acute care or for prevention. Preventive treatment consists of one 75 mg oral disintegrating tablet taken every second day. It works quite well as a preventive and has very few side effects. Nausea and abdominal discomfort occur in < 3% of patients. Some patients prefer to take a pill every other day over having an injection once per month or once every 3 months. It makes more sense for a woman of childbearing potential to take a drug with very short half-life vs one that lasts for 5 to 6 months in case she decides to become pregnant (or unexpectedly becomes pregnant).
A third gepant, atogepant (Qulipta™), was later approved, but only for prevention. It is available in 3 different strengths: 10 mg, 30 mg, and 60 mg. I tend to prescribe the 60-mg strength, and the dose is 1 pill every day.
If you compare rimegepant, which is taken once every other day, and atogepant, taken once daily, the latter tends to have slightly more side effects of nausea, drowsiness, and constipation, whereas rimegepant has been shown to have fewer side effects in double-blind, randomized studies. Like all gepants, it is quite effective and fast acting.