Efficacy, tolerability, and safety of erenumab for the preventive treatment of persistent post-traumatic headache attributed to mild traumatic brain injury: an open- label study

DOI: https://doi.org/10.1186/s10194- 020- 01136- z

Abstract-Summary We decided to assess the efficacy, tolerability, and safety of erenumab for preven- tion of persistent PTH attributed to mild traumatic brain injury.

A single-center, non-randomized, single-arm, open-label study of erenumab for

adults aged 18–65 years with persistent PTH.

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Post-concussion Syndrome

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Patients were assigned to receive 140-mg erenumab monthly by two subcutane-

ous 1-mL injections, given every 4 weeks for 12 weeks.

The primary outcome measure was the mean change in number of monthly head- ache days of moderate to severe intensity from baseline (4-week pretreatment period) to week 9–12.

The mean monthly number of headache days of moderate to severe intensity

was 15.7.

Of 100 patients who received at least one dose of erenumab, 2 patients discontin-

ued the treatment regimen due to adverse events.

Among patients with persistent PTH, erenumab resulted in a lower frequency of

moderate to severe headache days in this 12-week open-label trial.

Erenumab was well-tolerated as discontinuations due to adverse events were low. Placebo-controlled randomized clinical trials are needed to adequately evaluate

the efficacy and safety of erenumab in patients with persistent PTH.

Extended: Efficacy outcome measures were evaluated using a headache diary in

paper format, which does not allow monitoring of daily entries.

Introduction Post-traumatic headache (PTH) is a common sequela of mild traumatic brain injury (TBI) [12, 201], with a lifetime prevalence of 4.7% in men and 2.4% in women [202].

No pharmacological agent has been approved for the treatment of PTH. Clinicians often choose a preventive treatment based on the individual patients’

headache phenotype.

We find it timely to assess the efficacy, tolerability, and safety of erenumab for

preventive treatment of persistent PTH attributed to mild TBI.

Methods Patients were allowed to use one concomitant preventive headache medication taken at a stable dose, i.e. no changes to the dose within 2 months before the base- line phase.

The patients had five scheduled study site visits: screening, baseline (dose 1),

week 4 (dose 2), week 8 (dose 3), and week 12 (final evaluation).

Patients were instructed to complete a 4-week headache diary in paper format to establish headache characteristics and medication use (available in Supplement 2). During the open-label treatment phase, patients received 140-mg erenumab monthly by two subcutaneous 1-mL injections at study visits on baseline (day 1), week 4, and week 8.

At the follow-up visits (weeks 4, 8, and 12), protocol-specified study procedures were performed, and site investigators assessed efficacy and safety as well as head- ache diary compliance.

The latter included patients who received all three doses of erenumab and had at

least 80% compliance throughout the open-label treatment phase.

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Results Of the 11 patients who did not complete the open-label treatment phase, 8 patients were excluded due to protocol violations, i.e. lack of compliance with daily entries in the headache diary (n = 4), logistical issues (n = 3), and unwillingness to maintain stable dosing of a concomitant preventive medication during the treatment phase (n = 1).

Another patient withdrew due to personal issues related to a stressful life events, while two patients were excluded due to adverse events (n = 1, worsened headache; n = 1, dizziness).

The corresponding reduction was 3.0 ± 5.2 headache days of moderate to severe

intensity in patients with at least two preventive treatment failures.

No serious adverse events were reported, although two patients experienced adverse events (dizziness and worsened headache) that led to treatment discontinuation.

Discussion One randomized clinical trial (RCT) found that erenumab yielded a reduction of 1.8 migraine days by week 9–12 in patients with high-frequency episodic migraine who had failed at least 2 preventive treatments [203].

In a study of 91 patients with persistent PTH who had a migraine-like phenotype,

the mean monthly number of migraine-like days was 14.5 [162].

Our findings should be interpreted with caution, although they provide context to observations made by clinicians who currently use erenumab as an off-label preven- tive treatment for individuals with persistent PTH.

Ample data from migraine trials with erenumab have consistently shown a lower placebo response in patients who reported previous failure of preventive medica- tions [203–205].

As a migraine-like headache phenotype was present in 87 of the 100 included patients, it should be reasonable to assume that a similar placebo response is found in individuals with persistent PTH.

Conclusions The present study suggests that erenumab might be a useful preventive treatment for persistent PTH.

As discontinuations due to adverse events were low, further research is much needed to assess the effectiveness of erenumab against placebo as well as other preventive medications.

Acknowledgement A machine generated summary based on the work of Ashina, Håkan; Iljazi, Afrim; Al-Khazali, Haidar Muhsen; Eigenbrodt, Anna Kristina; Larsen, Eigil Lindekilde; Andersen, Amalie Middelboe; Hansen, Kevin John; Bräuner, Karoline Bendix; Mørch-Jessen, Thomas; Chaudhry, Basit; Antic, Sonja; Christensen, Casper Emil; Ashina, Messoud; Amin, Faisal Mohammad; Schytz, Henrik Winther 2020 in The Journal of Headache and Pain.

5.2

COVID-19 and SARS-COV2 Vaccines

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5.2

COVID-19 and SARS-COV2 Vaccines

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