Advances in Preventive Treatment of Migraine Continue 

At the Scottsdale Headache Symposium, the latest pharmacologic treatments for prevention of episodic migraine were reviewed. The focus remained on pharmacologic therapies that inhibit or block the effects of calcitonin gene-related peptide (CGRP) and its receptor—the first preventive treatments developed specifically for migraine. The most recent of these to be approved are in the -gepant class, rimegepant (Nurtec ODT; Biohaven, New Haven, CT) and atogepant (Qulipty; Abbvie, Lake Bluff, IL). Both atogepant and rimegepant were discussed in the context of migraine prevention goals of reducing attack frequency and duration, improving quality of life, and reducing disability.  

Rimegepant is the only treatment approved for both acute and preventive treatment of episodic migraine to date. In clinical trials rimegepant reduced migraine attack frequency by 4.3 left migraine days per month (MMD) vs a 3.5-day reduction in MMD with placebo. Safety and tolerability were similar between groups treated with rimegepant or placebo and no serious adverse events occurred. For acute treatment, rimegepant is taken as needed but not more than once every 24 hours. The rationale for this came from the randomized double-blind clinical trial that showed sustained reduction in migraine occurred 48 hours after treatment.  

Both in the clinical trials and in practice, nausea is the most common adverse event associated with rimegepant. Less common, but clinically significant are the potential drug interactions with rimegepant and other drugs that are metabolized by the CYP3 liver enzyme pathway and PGP and PCRP. Clinicians should be in the habit of checking for potential interactions when initiating rimegepant treatment for an individual.  

In clinical trials of atogepant, participants treated with 60 mg of atogepant had greater than 50% reductions in MMD, a higher proportion than seen with placebo. Atogepant is taken daily at 30 to 60 mg/day. Adverse events in clinical trials were mild and included fatigue, decreased appetite, and weight loss and were similar in people given 30 or 60 mg/day. This makes it attractive clinically to begin with the higher dose and this often done. However, it is important to note that in patients with severe renal impairment or end stage renal disease should receive only 10 mg/day and those with hepatic impairment should not use atogepant.  

Choosing among these therapies is recommended to occur after failed trials of older therapies both because of the availability of long-term safety data and because insurance companies may not reimburse new therapies, leaving patients with substantial financial burdens.  

Real-world implementation of all CGRP inhibitors for migraine prevention has been challenging both because people may be reluctant to try newer therapies or any therapy for prevention at all. There is now real-world data, however, showing no adverse cardiovascular events of any CGRP agents after as much as 3 years of clinical real-world use and longer for participants in people who participated in the trials. In addition, a recent study showed that discontinuation for adverse events was higher with the antiseizure medication vs erenumab, one of the monoclonal antibodies. Finally, it has also been shown that CGRP antagonists and botulinum toxin act synergistically with one another.  

These new data may increase not only the uptake of these new medications by patients, but also the willingness of insurers to reimburse for these therapies.