Migraine Treatment of the Month
Ubrelvy: Balancing Tolerability, Effectiveness and Flexibility
Calcitonin gene related peptide (CGRP) is a protein important to the signaling of head pain within the nervous system circuitry that generates migraine headache. Not surprisingly, CGRP has been a major focus of attention for years in research involving migraine therapeutics, and within the past two years six new therapies designed to block or disable CGRP have become available for general clinical use. Four of those therapies are monoclonal antibodies, all indicated for migraine prevention, and two are “gepants”, indicated for the treatment of acute migraine. One of these two gepants is ubrogepant (Ubrelvy), this issue’s “migraine treatment of the month”.
Ubrelvy is an orally administered tablet that is available in two doses, 50 and 100 mg. Ubrelvy exerts its therapeutic effect in migraine by blocking the receptor which CGRP must reach in order to conduct the electrochemical signal which produces acute migraine headache. In effect, Ubrelvy “short-circuits” the migraine circuitry.
Like the triptans, Ubrelvy is a “designer drug” that was developed specifically for the treatment of migraine, but Ubrelvy is NOT a triptan. The triptans are active at serotonin receptors—not CGRP receptors—
and while many migraineurs find the triptans to be effective in treating acute migraine, even those who experience headache relief often complain that the side effects associated with their use overshadow their benefit. In addition, one of the serotonin receptors which the triptans activate has the potential to cause arteries to constrict, and especially in patients with a history of vascular disease or potent vascular risk factors (such as poorly controlled hypertension), triptan use is discouraged.
Ubrelvy does not produce the familiar array of side effects associated with the triptans, and there is no contraindication to its use by patients with a history of vascular disease or with risk factors for vascular events such as heart attack or stroke. Unlike the triptans, Ubrelvy does not cause chest pressure or the sensation of “throat closure”, side effects which are annoying at best and, at worst, sufficiently alarming to cause patients to seek emergent medical evaluation.
For a significant proportion of migraineurs who use it, Ubrelvy is highly effective in treating acute migraine headache. In the clinical research trials which earned Ubrelvy its FDA approval, more than 60% of those who took the medication for headache of moderate or severe intensity experienced significant relief (to no or
mild pain) within 2 hours. A fifth of patients were entirely pain-free 2 hours after taking Ubrelvy.
In those same clinical trials, very few patients experienced side effects. The most common side effect, nausea, occurred in only 2% who took the 50 mg dose and in 4% administering the 100 mg dose, rates just slightly higher than that reported by patients receiving placebo.
The maximum recommended daily dose of Ubrelvy is 200 mg, and whether the initial dose of Ubrelvy administered is 50 mg or 100 mg, a second dose may be taken two or more hours after the first. Migraine can be stubborn, and given its all-too-frequent tendency to re-ignite, this dosing/
re-dosing flexibility can be useful for patients who experience headache persistence or recurrence after their initial dose of Ubrelvy. In the clinical research trials involving Ubrelvy, more than half of patients who achieved pain relief after their initial dose and then opted to take a second dose within the two days following their initial dose were free of headache within two hours of taking the second dose.
For many, Ubrelvy offers rapid relief from migraine headache and associated migraine symptoms without provoking unpleasant side effects. With two doses of proven safety, tolerability and efficacy and the option of repeat dosing, Ubrelvy offers the flexibility of a fast-onset oral triptan without triptan side effects or concerns regarding cardiovascular/cerebrovascular safety.