Migraine drug yields preventive benefits across the board in episodic, chronic migraine
Eptinezumab reduces migraine days for both episodic and chronic migraine patients, and the drug’s efficacy and safety profile are independent of age, sex, and body mass index (BMI), as shown in a study.
Pooled data from the phase III PROMISE-1 and PROMISE-2 trials showed that the ≥50-percent migraine responder rate (MRR) was always higher by ≥10 percent in both the 100- and 300-mg eptinezumab arms than in the placebo arm across most subgroups defined by demographic factors. [Clin Ther 2022;doi:10.1016/j.clinthera.2022.01.006]
Of note, the difference in ≥50-percent MRR rate did not exceed 10 percent between both eptinezumab doses and placebo in the class II obesity ((BMI >35 kg/m2) subgroup, as well as between the 100-mg dose and placebo across most subgroups (obesity classes I and II, patients with a migraine diagnosis between 20 and 30 years of age, and those with a diagnosis of migraine for <9 years). Just the same, there were still more eptinezumab-treated patients who achieved ≥50-percent MRR than those who received placebo.
In terms of safety, the migraine drug was associated with consistently low prevalence of treatment-emergent adverse events (TEAEs), with fewer patients experiencing serious and grade 3 events relative to the placebo group. The most common treatment-emergent adverse events were nasopharyngitis (6.2 percent, 8.2 percent, and 5.8 percent for eptinezumab 100 mg, 300 mg, and placebo, respectively) and upper respiratory tract infection (6.4 percent, 7.3 percent, and 6.1 percent, respectively).
The investigators pointed out that although migraine-preventive benefit of eptinezumab seemed to be weaker in patients with class II obesity, separate analyses of PROMISE-1 and PROMISE-2 did not reveal any pattern of association between weight and efficacy of the migraine drug. [Cephalalgia 2020;40:241-254; Neurology 2020;94:e1365-e1377]
“Although previous population pharmacokinetic analysis of eptinezumab has shown that body weight can affect eptinezumab clearance, the effect is small enough that dose adjustments based on weight are unnecessary, and this difference was not expected to have a large impact on eptinezumab efficacy,” the investigators said. [Pharmacol Res Perspect 2020;8:e00567]
“In addition, a phase I study of healthy subjects randomized to receive eptinezumab 100 mg or placebo with a BMI between ≥25 and <40 kg/m2 in the 2 months before screening found that [the migraine drug] was safe and well tolerated,” they continued. [Endocrinol Diabetes Metab 2021;4:e00217]
The study was limited by its post hoc design. The investigators acknowledged that there might be differences across subgroups for episodic or chronic migraine that were masked by pooling PROMISE-1 and PROMISE-2. Furthermore, some of the subgroups had small sample size, which limited the statistical power for detecting significant differences between eptinezumab and placebo.
The investigators also stressed that it was not possible to identify which type of patients respond better to higher doses of the migraine drug.
Nevertheless, the findings indicate that most patient characteristics captured across the PROMISE-1 and PROMISE-2 clinical trials do not impact the efficacy, safety, or tolerability of eptinezumab in the prevention of migraine, they said.