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

Abstract

Background: Calcitonin gene-related peptide (CGRP) has recently been implicated in the pathogenesis of post-traumatic headache (PTH), which raises the prospect for therapeutic use of monoclonal antibodies targeting CGRP or its receptor. Therefore, we decided to assess the efficacy, tolerability, and safety of erenumab for prevention of persistent PTH attributed to mild traumatic brain injury.

Methods: A single-center, non-randomized, single-arm, open-label study of erenumab for adults aged 18-65 years with persistent PTH. Patients were assigned to receive 140-mg erenumab monthly by two subcutaneous 1-mL injections, given every 4 weeks for 12 weeks. The primary outcome measure was the mean change in number of monthly headache days of moderate to severe intensity from baseline (4-week pretreatment period) to week 9 through 12. Tolerability and safety endpoints were adverse events (i.e. number and type).

Results: Eighty-nine of 100 patients completed the open-label trial. At baseline, the mean monthly number of headache days of moderate to severe intensity was 15.7. By week 9 through 12, the number was reduced by 2.8 days. The most common adverse events were constipation (n = 30) and injection-site reactions (n = 15). Of 100 patients who received at least one dose of erenumab, two patients discontinued the treatment regimen due to adverse events.

Conclusions: Among patients with persistent PTH, erenumab resulted in a lower frequency of moderate to severe headache days in this 12-week open-label trial. In addition, 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.

Trial registration: ClinicalTrials.Gov, NCT03974360. Registered on April 17, 2019 - Retrospectively registered.

Keywords: Clinical management; Concussion; Head injury; Head trauma; Secondary headache.

Conflict of interest statement

The authors declared the following potential conflicts of interest with respect to the research, authorship and/or publication of this article: Dr. Casper Emil Christensen has lectured and been a scientific advisor for Teva. Dr. Messoud Ashina has received personal fees from Alder BioPharmaceuticals, Allergan, Amgen, Eli Lilly, Novartis, and Teva. Dr. Messoud Ashina has been or currently is a principal investigator on clinical trials for Alder, Amgen, electroCore, Novartis, and Teva. Dr. Messoud Ashina also serves as an Associate Editor of Cephalalgia, Associate Editor of Headache, and Co-Editor of the Journal of Headache and Pain. Dr. Messoud Ashina reports research grants from Lundbeck Foundation, Novo Nordisk Foundation, and Research Foundation of the Capital Region of Denmark. Dr. Faisal Mohammad Amin has received personal fees from Eli Lilly, Novartis and Teva. Dr. Faisal Mohammad Amin is currently a principal investigator on clinical trials for Novartis and Teva. Dr. Faisal Mohammad Amin also serves as an Associate Editor of Headache Medicine. Dr. Henrik Winther Schytz has received speaking fees from Novartis and Teva. The other authors declare no conflicts of interest.

Figures

Fig. 1

Flow of Participants in an Open-Label Study of Erenumab for Prevention of Persistent Post-Traumatic Headache attributed to Mild Traumatic Brain Injury

Fig. 2

Overview of 25%, 50%, and 75% Responder Rates. The responder rates were calculated as a percent reduction from baseline to week 9 through 12 in the number of headache days of moderate to severe intensity