Dr. Friedman also recommended prevention therapy for patients with unusual migraine types such as those that are hemiplegic or with brainstem aura, regardless of frequency.
Among the CGRPs, clinicians have the most experience with erenumab, which was the first drug to be approved by the FDA. “But if patients don't improve on it, or have side effects, I prescribe fremanezumab or galcanezumab,” said Dr. Silberstein.
Dr. Wells asks her migraine patients to complete headache logs to track their frequency and “directly assess improvements,” she said, “not only for our benefit but also for insurance companies who require this data.”
Costs and Access
The cost of the CGRP drugs is high — erenumab costs $575 per month, for example. As a result large health insurers, expecting a flood of expensive prescription claims for erenumab, have established requirements that patients document the number of headaches they suffer per month, as well as provide proof they have failed on at least two drugs.
“If it weren't for these drug-failure requirements and [their] cost, the CGRP drugs could be used as a first-line therapy,” said Dr. Friedman. “In addition, practice resources are strained when staff have to spend a lot of time requesting prior authorizations from insurance companies, and when providers must hold peer-to-peer conversations,” she said.
Some commercial insurers also want patients to stop receiving onabotulinumtoxinA (Botox) for four months before starting CGRP drugs, according to Dr. Friedman. “Most patients on onabotulinumtoxinA are getting some benefit, but not enough,” she said. “But to expect them stop the treatment and return to baseline, which by definition is chronic migraine and severe, is a cruel and unusual punishment. A more rational approach is to leave patients on onabotulinumtoxinA while they are starting a CGRP drug, and then depending on their response, titrating them off onabotulinumtoxinA.”
“Since we have limited experience prescribing these drugs, we also don't know about their long-term efficacy and the timing of switching between the different CGRPs,” said Dr. Wells.
The long-term safety and side effects of CGRPs are also unknown. Amgen and Novartis, which make and track prescriptions of erenumab, reported that more than 100,000 scripts were written since May without major safety signals, according to Dr. Wells.
Another unknown is whether pregnant women can take CGRPs without risks to their fetuses. “I do not prescribe or recommend this for anyone who is pregnant, and I advise patients that if they become pregnant while on this medication, they stop taking the treatment immediately,” said Dr. Wells.
Before patients of childbearing age start taking CGRPs, Dr. Wells recommends a pregnancy test if there's any uncertainty about their pregnancy status. “If they want to get pregnant in the future, I recommend they stop the drugs and wait about six months before starting to conceive,” she said.
The migraine specialists agreed that more clinical practice data is needed to better understand the long-term effects and implications of prescribing CGRPs. “We also want to know whether taking these drugs decrease[s] medical utilization such as emergency department visits and hospitalizations associated with migraines,” said Dr. Rosen. “If that's the case, it is very likely that these medications will be covered by insurers.”
Dr. Silberstein would like more clinical studies to investigate why some people don't respond to CGRPs: Is it because there are parallel mechanisms for migraine, or because some people make too much CGRP, which overwhelms the antibody?
In the meantime, more CGRPs are in the pipeline Clinical trials also showed that galcanezumab was effective in preventing episodic cluster headaches, although the data have not been submitted to the FDA yet for this indication. Fremanezumab is also being studied for this possible indication, but the trial data have not been released yet, according to Dr. Silberstein.
Small-molecule oral CGRP receptor antagonists — ubrogepant (MK-1602) and rimegepant (BHV-3000) — have met clinical endpoints in phase 3 studies for the acute treatment of migraine. Atogepant demonstrated efficacy for acute migraine prevention in phase 2b/3 clinical trials, said Dr. Friedman.
“These medications offer a safe acute treatment option for patients with cardiovascular disease who can't take triptans,” she said. “They also do not produce the side effects of triptans, including chest tightness, fatigue, nausea, dizziness, drowsiness, tingling, and asthenia.”
“We will see a lot of advances in headache medicine in the next three to five years, which is exciting. As health care providers, we have a responsibility to help patients navigate these new options and make wise decisions,” said Dr. Rosen.
Dr. Wells reported no disclosures. Dr. Friedman has received honoraria from Alder Biopharmaceuticals, Allergan, Amgen, Biohaven, Eli Lilly, Teva, Promius, electroCore, and Zosano. Dr. Rosen serves on the advisory boards and receives honoraria and travel expenses for Allergan, Amgen, Avanir, Biohaven, Eli Lilly, Promius, Supernus, and Teva. Dr. Silberstein is a consultant and/or advisory panel member and has received honoraria from Abide Therapeutics; Alder Biopharmaceuticals, Allergan, Amgen, Avanir, Biohaven, Cefaly, Curelator, Dr. Reddy's Laboratories, Egalet Corporation, GlaxoSmithKline Consumer Health Holdings, eNeura, electroCore Medical, Lilly USA, Medscape, NINDS, Satsuma Pharmaceuticals; Supernus, Teva, Theranica, and Trigemina, Inc.
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