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

Håkan Ashina,Amalie Middelboe Andersen,Henrik Winther Schytz,Anna Kristina Eigenbrodt,Thomas Mørch-Jessen,Eigil Lindekilde Larsen,Haidar Muhsen Al-Khazali,Karoline Bendix Bräuner,Afrim Iljazi,Sonja Antic,Messoud Ashina,Basit Chaudhry,Faisal Mohammad Amin,Kevin John Hansen,Casper Emil Christensen

doi:10.1186/s10194-020-01136-z

Abstract

BackgroundCalcitonin 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.MethodsA 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).ResultsEighty-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.ConclusionsAmong 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 registrationClinicalTrials.Gov, NCT03974360. Registered on April 17, 2019 - Retrospectively registered

Highlights

Post-traumatic headache (PTH) is a common sequela of mild traumatic brain injury (TBI) [1, 2], with a lifetime prevalence of 4.7% in men and 2.4% in women [3]
Among patients with persistent posttraumatic headache (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

Summary

Introduction

Post-traumatic headache (PTH) is a common sequela of mild traumatic brain injury (TBI) [1, 2], with a lifetime prevalence of 4.7% in men and 2.4% in women [3]. Clinicians often choose a preventive treatment based on the individual patients’ headache phenotype This approach has not been systematically investigated and, lacks evidence. There remains a considerable unmet need for mechanism-based treatments that are effective and well-tolerated In this context, monoclonal antibodies targeting calcitonin gene-related peptide (CGRP) or its receptor might hold great promise as PTH often mimics a migraine-like headache [6] and anti-CGRP monoclonal antibodies have proven effective for preventive treatment of migraine [7–11]. Preclinical data have emerged and demonstrated hypersensitivity to CGRP in concussed rodents [12, 13] We find it timely to assess the efficacy, tolerability, and safety of erenumab for preventive treatment of persistent PTH attributed to mild TBI. We decided to assess the efficacy, tolerability, and safety of erenumab for prevention of persistent PTH attributed to mild traumatic brain injury

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