Standard 12-Week BoNTA Interval May Not Be Beneficial for Chronic Migraine

woman headache stress
woman headache stress
Investigators examined patient-reported wearing-off effect of the antinociceptive benefit of onabotulinumtoxinA near the end of the 12-week treatment cycle in patients with chronic migraine.

The standard 12-week onabotulinumtoxinA (BoNTA) injection interval for chronic migraine (CM) may not be clinically beneficial in all patients, according to study results published in Headache.

This retrospective study included patients with CM who completed a minimum of 2 treatment cycles of BoNTA therapy at a single center by a single neurologist from January 2014 to March 2018 (N=98) in the analysis. Researchers reviewed patient-reported wearing-off effect (WOE), defined specifically as “worsening headache and/or neck pain … that occurred during the 4 weeks (28 days) prior to the scheduled reinjection of BoNTA.” They also examined details regarding the onset and the number of days with perceived symptoms but did not consider any WOE events with an obvious confounding factor.

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Researchers analyzed 471 eligible treatment cycles. A total of 43 patients reported ≥1 occurrence of WOE during the study period. In the group reporting 1 WOE event (n=24/43), the median dose of BoNTA was 165 units and the median duration of the antinociceptive effect was 66.5 days; 21% (5/24) of these patients reported use of abortive therapy to manage symptoms related to WOE events. In patients reporting ≥2 WOE events (n=19/43), the median dose was 167 units and the median duration of the antinociceptive effect was 65.3 days; 32% (6/19) of patients in this group reported use of abortive therapy for symptoms related to WOE events.

Limitations of this study include its retrospective design and small sample size. This study was not designed to assess the effectiveness of BoNTA in CM. Patient headache and symptom diaries were not maintained to accurately assess the onset and number of days with perceived symptoms; the burden of headaches were not systematically assessed. Recall bias was inevitable, given that pain is a subjective measurement and the calculation of the duration of the antinociceptive effect of BoNTA was crude. Other limitations include the single site and single provider.

According to a reported WOE occurrence sooner than the anticipated duration of the antinociceptive effect of BoNTA on patients with CM, researchers proposed that the standard 12-week injection interval is not clinically beneficial for all patients.

“The relative increase in headache and pain symptoms associated with an increase in the use of abortive therapies has a potentially negative effect on quality of life with a higher risk of disease progression,” the researchers concluded. “Shorter injection intervals may quite possibly also yield efficacy in a broader population of sufferers of CM (deemed as nonresponders to BoNTA) as well as patients with episodic migraine and tension headache.”

Disclosure: One study author declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of author’s disclosures.


Khan FA, Mohammed AE, Poongkunran M, Chimakurthy A, Pepper M. Wearing off effect of onabotulinumtoxinA near the end of treatment cycle for chronic migraine: a 4-year clinical experience [published online November 22, 2019]. Headache. doi:10.1111/head.13713