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The observational study found no increase in migraine days at the end of treatment months for patients on erenumab or fremanezumab.
Faisal M. Amin, MD, PhD
In a real-world observational study of patients with chronic migraine, data showed that treatment with erenumab (Aimovig; Amgen) or fremanezumab (Ajovy; Teva Pharmaceuticals) was not associated with a wearing off effect among responders and was consistent with their respective phase 3 premarketing studies. Investigators concluded that all patients should upfront be informed about the no wearing-off effect to avoid potential migraine attacks generated by the nocebo effect.
Published in Cephalalgia, the single-center, observational study included 60 patients on monthly injections of 140 mg of erenumab and 40 patients on 225 mg of fremanezumab. The primary end point, wearing-off effect, was defined as an increase of at least 2 weekly migraine days in the last week compared with the second week over 2 consecutive 4-week treatment periods. At the time of inclusion, the average days of treatment was 177.4 (SD, 96).
Led by senior investigator Faisal M. Amin, MD, PhD, an associate professor at the University of Copenhagen, results showed no difference in migraine days between week 2 (2.30 [±0.15]) and week 4 (2.37 [±0.12]) over 2 consecutive treatment months (3.04%; P = .558). The data revealed no difference in migraine days during these weeks in the ernumab (P = .194), nor the fremanezumab (P = .581) groups, as well as no between-group difference in treatments throughout that time. An explorative analysis demonstrated no association between wearing-off and response rate in the total group (P = .935) or within the erenumab (P = .811) and fremanezumab (P = .981) groups.
"The wearing-off effect is more than an academic interest as patients may ask their clinician about the risk of wearing-off or for more frequent injections," the study authors wrote. "The latter may be the result of a fear of having migraine attacks at the end of the treatment period, especially in those patients who experience a good effect during the treatment period. This anxiety (i.e. nocebo) can by itself generate migraine days in some patients."
Amin et al added, "Patients should be informed about this fact based on available evidence rather than experimenting with shorter injection intervals. Furthermore, it is uncertain whether more frequent treatment will produce the same tolerability."
A secondary end point examined patients who had at least a 30% reduction in monthly migraine days, compared with baseline, in the 2 consecutive treatment months. Overall, results showed no difference in migraine days between week 2 (1.43 [±0.12]and week 4 (1.52 [±0.16]) over this time period in this subgroup of patients (2.6%; P = .573).
From weeks 1-3 to week 4, there was no difference in weekly migraine days in both the general cohort and those who were at least 30% responders. Explorative analysis showed no association between response rate and wearing-off effect from week 1 to week 3 compared to week 4 in the total group (p = 0.626) or within the erenumab (p = 0.634) and fremanezumab (p = 0.902) groups.
Among a subgroup of 81 patients (81%) who were on either study treatment for at least 3 months at the time of inclusion, results showed no difference in migraine days from weeks 1-3 (1.93 [±0.13]) to week 4 (2.06 [±0.10])(6.7%; P = .191) in the subgroup or within the erenumab (P = .237) and fremanezumab (P = .534) groups individually. Notably, there was no association of response rate and wearing-off between week 2 and week 4 (p = 0.610) or from weeks 1–3 to week 4 (p = 0.882).
"Consistency is important when examining wearing-off effects in patients. Increase in migraine days in the last week of the treatment month may be a coincidence or attributed to random causes (e.g. common upper respiratory tract infection, sleep disturbance or menstruation)," Amin et al wrote. "However, if the patient experiences an increase in migraine days in the last week of the month in two or more consecutive treatment periods, random causes are less likely, and the increase may represent a true wearing-off effect. Consequently, we included two treatment months in this study."
