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 posttraumatic 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.

Hypersensitivity to Calcitonin Gene–Related Peptide in Post‐Traumatic Headache

“…One recent open-label study reported promising data suggestive of CGRP antagonism having therapeutic benefit in prevention of persistent PTH. 12…”

“…8 Intravenous infusion of CGRP provokes migraine attacks in patients with migraine, 9,10 and CGRP antagonism has proven beneficial for the acute and preventive treatment of migraine. 11 In support of CGRP involvement in PTH, one open-label study found that CGRP antagonism might have therapeutic benefit in patients with persistent PTH, 12 and two animal studies reported findings suggestive of hypersensitivity to CGRP in concussed rodents. 13,14 Thus, it is timely to ascertain whether, and if so by what mechanisms, CGRP is involved in the genesis of persistent PTH.…”

The analysis of calcitonin gene-related peptide – a narrow path between useful and misleading findings

“…In this context, preclinical studies show that mechanisms involving CGRP drive TBI-related development of central sensitization as well as the response to bright light stress and may therefore be relevant for the expression of PTH ( 11 ). In line with these findings, erenumab, a monoclonal antibody targeting the CGRP receptor, has been shown to reduce headache intensity in PTH ( 12 ). These findings strongly support a role of CGRP in PTH.…”

Position Paper on Post-Traumatic Headache: The Relationship Between Head Trauma, Stress Disorder, and Migraine

“…This finding may support the use of CGRP modulators in the acute and preventive treatment of PTH. If the mechanisms driving the persistent head pain in PPTH are shared with those of CM, then it is likely that a subgroup of patients with PPTH with a CM phenotype will benefit from these approaches [68].…”

“…The role of CGRP monoclonal antibodies in PTH is being studied. Initial open-label shortterm evidence on the effectiveness of erenumab in PPTH with a predominant CM phenotype showed a meaningful response in 28% of the patients, which is lower than the responder rate that emerged from the CM studies in difficultto-treat populations [74][75][76]. Fremanezumab is being studied for the treatment for PTH in a phase 2 multicentre randomized controlled study (ClinicalTrials.gov Identifier: NCT03347188).…”