There is little evidence of systemic erenumab wearing-off among patients with chronic or episodic migraine, according to a post hoc analysis published in the journal Headache.
Erenumab is a monoclonal antibody drug delivered by monthly injection and was developed to prevent migraine. Some anecdotal evidence has suggested erenumab has a wearing-off effect, in which some patients have a return of migraine in the week prior to their next dose.
This analysis evaluated the potential wearing-off effect of erenumab among patients with episodic migraine (EM) with ³4 to <15 migraine days and <15 headache days per month or chronic migraine (CM) with ³8 migraine days and ³15 headache days per month. Data were sourced from 4 double-blind randomized trials conducted in North America, Europe, Russia, Turkey, and Japan. Wearing-off was assessed by comparing the number of weekly migraine days in week 4 with the number of weekly migraine days during weeks 1 to 3 of each treatment cycle.
The patients who received 70 mg or 140 mg erenumab (n=1407) and placebo (n=864) were included in this analysis. Baseline demographics were generally well-balanced between study treatment groups. The patients were median age, 41-45 years, 84.6%-86.8% were women, and 58.8%-95.6% were taking acute migraine-specific medications. The use of migraine-specific medications was higher in the study conducted in Japan compared with the other study sites.
Overall, the wearing-off effect was minimal, in which weekly migraine days differed between week 4 and weeks 1 through 3 by less than 1 day among either the erenumab recipients or placebo recipients.
Among only responders, (placebo: 10.7%-27.8%; 70 mg erenumab: 19.1%-43.3%; 140 mg erenumab: 24.6%-51.9%) there was a subgroup of patients who experienced wearing-off, however, a similar proportion of erenumab and placebo recipients experienced the wearing-off effect.
Persistent wearing-off, defined as 2 or more consecutive months of wearing off, was observed among 3.3%-3.4% of placebo recipients, 0.0%-2.2% of 70 mg erenumab recipients, and 4.2%-4.3% of 140 mg erenumab recipients.
Stratified by consistent response, defined as ³50% reduction of weekly migraine days over the first 3 weeks of the cycle for 2 or more consecutive cycles, 10.7%-11.0% of placebo, 19.1%-50.0% of 70 mg erenumab, and 35.3% of 140 mg erenumab recipients were consistent responders. Persistent wearing-off was observed among 14.3%-20.0% of the placebo, 4.2%-5.6% of the low-dose erenumab, and 4.2% among the high-dose erenumab groups.
No difference in erenumab steady-state serum concentrations at week 12 were observed on the basis of wearing-off.
The major limitation of this study was the short study durations. It remains unclear whether trends in wearing-off may change in the long-term.
The researchers noted that erenumab likely did not have a significant wearing-off effect during 6 months of treatment for migraine.
They concluded that, “Further research is needed to determine if wearing-off reported by some patients in clinical practice reflects a vulnerable and identifiable subgroup or is just reflective of normal fluctuations in migraine frequency or to cyclic fluctuations in a subgroup of patients.”
Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.
Dodick DW, Blumenfeld AM, Singh RBH, et al. Post hoc analysis of clinical trial data and pharmacokinetic data to assess wearing-off of erenumab within monthly treatment cycle. Headache. Published online October 13. doi:10.1111/head.14403