Treatment of posttraumatic headache migraine phenotype with erenumab – An observational study

Introduction

The prevalence of posttraumatic headache (PTH) is approximately three million of which 20% are adolescence. ¹ Most patients who present with PTH will manifest migraine phenotype which has all the characteristics of migraine with and without aura.^2,3 All patients represented in this observational study fell under the International Classification of Headache Disorders-vs 3 (ICHD3) classification as acute headache attributed to mild traumatic injury to the head 5.1.2. ⁴ The PTH phenotype was migraine: typical features include throbbing pounding headache, photophobia, nausea, vomiting, visual aura, brainstem aura, and inability to engage socially, in school, or work. Most of these patients are treated with preventatives used in non-traumatic migraine patients, but the response is usually inadequate.

Erenumab is a CRRP-receptor monoclonal antibody which is Food and Drug Administration (FDA)approved for the preventative treatment of migraine. It has an excellent safety profile, impressive efficacy data, can be effective as quickly as one week, and has virtually no adverse effects except for very low incidence of injection site reactions and constipation. Erenumab was the first of the three current FDA approved CGRP monoclonal antibodies. It is the only antibody targeting the CGRP receptor. Of the three FDA approved CGRP monoclonal antibodies, erenumab has the longest (3 yr) open label extension data. ⁵ Six patients were treated with erenumab with clinical migraine phenotype following PTH.

Methods

All patients met the criteria for migraine with or without aura as delineated in ICHD3. The etiology of their migraines was head trauma which was defined as PTH secondary to mild traumatic injury to the head. All patients had normal exams and head imaging. Three patients had a remote history of migraine six months or longer with symptoms that differed from the PTH-induced migraine phenotype and their history of migraine. General informed consent was obtained from all patients. Erenumab is FDA approved for the preventative treatment of migraine with and without aura. An AHS publication recently recommended using CGRP mAbs in the pediatric population where other preventives have failed or not tolerated. ⁶ All patients failed prior treatments and were disabled from migraine with intense high-frequency headache, and inability to work, attend school, or engage in social circles. Ineffective preventative treatments given for at least four weeks alone or in combination which were discontinued with erenumab administration included daily topiramate, amitriptyline, gabapentin, doxepin, venlaxafine, memantine, ibuprofen, naproxen, and ondesterone. Abortives such as non-steroidal anti-inflammatory drugs (NSAIDS) triptans, or over the counter non prescription (OTC) analgesics were allowed but were never taken daily and their need tapered off quickly with the rapid response to erenumab. The patients were relatively healthy and confounding variables such as non-morbid obesity and concurrent minor illnesses were not significant to be considered in the outcome analysis. No patient had medication overuse headache syndrome, pregnancy, secondary gain motivation, or psychiatric disorders. Baseline monthly headache days (MHDs) and Head Impact Test-6 (HIT-6) were recorded and restated two months after receiving erenumab 140 mg. Only one patient (patient 5) required a second dose, and the MHD and HIT-6 were recorded two months after the second dose. Doses were administered in the office by a certified medical assistant. Data were assessed retrospectively.

Discussion

These seven patients were severely symptomatic from migraine that followed mild posttraumatic head injury. Each patient went from severe disability to no headache disability and 95% reduction of MHDs with the reduction often commencing within a few weeks of receiving erenumab 140 mg. There were no adverse effects.

The real impact of erenumab on these patients was striking. Patient 6 was a 29 y/o laborer who fell off a truck, hit head, and experienced daily migraine with no history of migraine. For 11 weeks he could not return to work and was unresponsive to vestibular therapy, topiramate, amitriptyline, gabapentin, and non-daily triptan and NSAID abortives. Three weeks after one dose of erenumab, he went back to work with rare headaches. Patient 4 was a 15 y/o male student wrestler who was thrown to the floor during wrestling with head trauma, had daily migraines and could not attend school due to severe pounding headaches and photophobia worsened with academic engagement. Within five days of erenumab, he was asymptomatic and back to his academic classes.

There are no FDA approved treatments for PTH with migraine phenotype. Studies have shown that conventional treatment of PTH migraine phenotype results in 26% relief and 74% no relief.^7,8 Differences in regional volumes, cortical thickness, surface area, and curvature were noted comparing PTH migraine phenotype to migraine patients using functional magnetic resonance imaging. ⁹ However, CGRP receptors are ubiquitous in the cortex of the entire brain. ¹⁰ The trigeminal vascular access of CGRP-R mAbs via the meninges may explain the robust response of these patients to erenumab. Perhaps there is amplification of the trigeminovascular system in PTH migraine phenotype which would account for the failure of conventional migraine preventatives which do not directly antagonize CGRP receptors which is the mechanism of action of erenumab. The presence of pre- and postsynaptic receptors can explain the efficacy of CGRP-mAbs. In a rat model of concussion, headache and pain-related behaviors were mediated through a CGRP-dependent mechanism. Concussed rats’ tactile pain and hypersensitivity were inhibited by anti-CGRP antibody treatment. ¹¹

Conclusions

This is a small observational study on the effect of erenumab on patients with PTH-migraine phenotype with no control group. A placebo effect cannot be excluded, and the original studies that led to FDA approval of erenumab for episodic and chronic migraine demonstrated efficacy with a placebo effect of approximately 30%. None of these patients had psychiatric or secondary gain issues, or currently active preexistent migraine. Many had failed previous migraine preventatives. The efficacy and safety of erenumab 140 mg in the virtual elimination of migraine was extremely impressive with no adverse effects. Concussion with PTH migraine phenotype is a public health problem. This pilot observation study should lead to larger studies to validate these findings and determine if erenumab, which is safe and effective, should be in the forefront for the treatment of PTH with migraine phenotype.