Which Outcomes Should Be Prioritized When Determining Migraine Preventive Treatment Efficacy?

Intensity of headache pain is as important as frequency when evaluating the clinical response and impact of migraine preventive treatment with OnabotulinumtoxinA on patient headache-related disability, according to a recent study.

Intensity of headache pain is as important as frequency when evaluating the clinical response and impact of migraine preventive treatment with OnabotulinumtoxinA on patient headache-related disability, according to a study published in The Journal of Headache and Pain.

“Suffering recurrent migraine attacks produces an abrupt and non-predictable functional disruption of daily life and entails an overwhelming decrease in the patient’s quality of life with a clear negative impact on a personal, family, working, social and economic level,” authors write.

In order to accurately evaluate treatment response in daily clinical practices, providers need to establish which headache-related outcomes have a more relevant impact on patients’ lives.

“As neurologists and headache specialists, in the absence of treatments that dramatically change the course of migraine, our main goal when treating a patient with chronic migraine is to recognize and minimize headache-related disability,” researchers said.

Currently, the International Headache Society Guidelines for clinical trials of preventive migraine treatment consider change in migraine days, change in moderate to severe headache days, or responder rate as primary clinical trial endpoints. However, trials often include secondary endpoints like headache intensity, headache free days, and duration of effect.

In an observational prospective study, investigators evaluated the relevance of clinical trial endpoints in clinical real-life disability improvement in response to migraine preventive treatment with OnabotulinumtoxinA.

Data from 395 patients were included in the study, which assessed 8 headache-related and acute medication use endpoints recommended by the Guidelines of the International Headache Society for controlled trials of preventive treatment of chronic migraine.

At baseline, all patients exhibited chronic migraine with an average headache frequency 26.5 (standard deviation [SD]) 5.2 headache days/month. The majority of participants (85.1%) were also female.

After 6 months, researchers evaluated impact on disability improvement in those treated with OnabotulinumtoxinA. Responders in disability were defined as patients with ≥50% Migraine Disability Assessment (MIDAS) score reduction after 2 cycles of treatment. An analysis to measure the impact of improvement in the evaluated outcome measures according to perceived disability in clinical practice was then carried out.

Analyses found:

  • After 6 months, 49.1% of patients were headache-related disability responders
  • There was a statistically significant reduction in headache frequency (26.5&thinsp;[SD]&thinsp;5.2 to 15.2&thinsp;[SD]&thinsp;10.1 headache days/month, P &thinsp;<&thinsp;.001) with 51.4% (203/395) of patients experiencing a ≥&thinsp;50% frequency reduction
  • Headache pain intensity reduction was rated as ≥50% in 35.8% (141/395) of patients and analgesics intake was cut in half in 60.4% (239/395) of patients
  • Variables independently associated to disability improvement were headache days reduction (P&thinsp;=&thinsp;.02) and&thinsp;≥&thinsp;50% pain intensity reduction (P&thinsp; = &thinsp;.04)
  • A&thinsp;≥&thinsp;50% reduction in headache frequency or pain intensity showed similar influence on disability improvement after treatment

“We demonstrate in a clinical sample of patients with chronic migraine that, after 6&thinsp;months of treatment with OnabotulinumtoxinA, headache frequency reduction is not the only outcome independently associated with MIDAS improvement but also pain intensity, [which] should be considered also as a major clinical outcome measure,” authors write.

In other words, individuals without a significant improvement in headache frequency but whose headache intensity improved reported similar impact on disability (determined by MIDAS scores) as individuals whose frequency improved.

The study’s main limitation is its sole investigation into effects of OnabotulinumtoxinA. Future studies on chronic and episodic migraine ought to include responses to oral and calcitonin gene related peptide monoclonal antibodies, taking into consideration both changes in frequency and intensity of migraine.

“A preventive treatment that has an impact on the severity of the attacks, reduces the patient’s disability in the same way as a reduction of ≥50% or more in headache frequency,” researchers conclude.


Torres-Ferrus M, Gallardo VJ, Alpuente A, et al. Influence of headache pain intensity and frequency on migraine-realted disability in chronic migraine patients treated with onabotulinumtoxinA. J Headache Pain. Published online July 11, 2020. doi:10.1186/s10194-020-01157-8