Debating the Evidence in Switching CGRP Therapies for Migraine

If patients with migraines fail to respond to a monoclonal antibody, can they be switched to another?

During a discussion at the Migraine Trust International Symposium, 2 neurologists engaged in a theoretical debate about whether patients can switch from one calcitonin gene-related peptide (CGRP) inhibitor to another.

In the United States, there are now 4 CGRP therapies on the market: erenumab (Aimovig), fremanezumab (Ajovy), Emgality (galcanezumab), and eptinezumab (Vyepti).

Despite the fact that the CGRP antibodies are taken on different schedules and in different ways, they can indeed be switched, depending on patient response, according to Andrew C. Charles, MD, a professor of neurology at UCLA and director of the UCLA Goldberg Migraine Program.

Switching medications is something that is done routinely with other classes of medications for migraines, he said, citing triptans, beta blockers, and nonsteroidal anti-inflammatory drugs.

He reviewed the differences of the 4 available treatments in terms of dosing, half life, the degree of humanization, kinetics, and whether the CGRP antibody targets the receptor or the peptide.

“So the question is, do these differences, actually, confer differences in terms of efficacy or tolerability? Unfortunately, we don't really have any head-to-head evidence that guides us in terms of comparing one antibody to the other,” Charles pointed out.

Charles used the real-world experience of approximately 2500 patients at UCLA to frame his thinking. Patient age spanned 15 to 82 years old, he said, and most had health insurance. About 40% were on erenumab, about 40% were on fremanezumab, and about 20% were on galcanezumab.

Patients described the medications as life-changing, he said, adding that “the efficacy exceeds that observed in the clinical trials with reduced migraine and headache days, reduced acute medication use, improved quality of life. They are effective even in patients who have failed other preventative medications.”

Constipation has been more common than what was reported in the trials, especially for erenumab. Other complaints include a worsening of Reynaud syndrome, fatigue, hair loss, sexual dysfunction, and in women, some reports of irregular menstrual periods.

Some patients also lose responsiveness to treatment after a few months, Charles said.

“So these are reasons to switch: if there’s inadequate efficacy or adverse effect,” he said.

He also described one case where a patient was switched from one CGRP to another to see if the improvements could be even more striking. The male patient, 34, went on erenumab and saw his headache days fall from a high of 12 days per month to 4 days per month. Switching to galcanezumab led to a total elimination of his migraines; however, he developed persistent generalized uticaria for 3 weeks straight. The man went back on erenumab, and lives with 4 headache days per month.

In the United States, the only issue with switching medications, Charles said, is cost, as it depends on insurance and on which drugs are included in formularies.

“If there wasn’t the issue of expense, we wouldn’t even be having this debate,” he said.

In an attempt to show that the antibody treatments cannot be switched that easily, Patricia Pozo Rosich, MD, PhD, a neurologist at the Vall d’Hebron University Hospital in Barcelona, Spain, head of its Headache and Craniofacial Pain Unit, and director of the Headache and Neurological Pain Research Group, said there is a scarcity of published literature discussing the issue.

“The absence of evidence is not the evidence of absence,” she said, quoting the astronomer Carl Sagan.

As one example, she said that some nonresponders to certain CGRP medications may just be moving through different cycles of migraine, which may shift and change over time depending on age, gender, and lifestyle habits.

In addition, due to the lack of reported data from both patients and clinicians, it is unknown how long people have been on CGRP therapies before a switch takes place, she said.

Pozo Rosich also said there is an “absence of biological evidence” as well as a difficulty of agreeing what constitutes treatment failure.