An outstanding scientific question, that merits further investigation, is whether dilation of intracranial arteries is implicated in the pathogenesis of cephalic pain in migraine. Here, we hypothesize that experimentally-induced dilation of intracranial arteries using intake of sildenafil (a potent vasodilator) can induce cephalic pain with migraine-like features in people with migraine, who prior to the infusion are administered erenumab (anti-calcitonin gene-related peptide (CGRP) receptor monoclonal antibody.

An outstanding scientific question, that merits further investigation, is whether dilation of intracranial arteries is implicated in the pathogenesis of cephalic pain in migraine. Here, we hypothesize that experimentally-induced dilation of intracranial arteries using intravenous infusion of levcromakalim (a potent vasodilator) induces cephalic pain with migraine-like features in people with migraine, who prior to the infusion are administered erenumab (anti-calcitonin gene-related peptide (CGRP) receptor monoclonal antibody).

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TNP are a considerable burden and affects significantly the quality of life of the sufferer. There are medications for their management but while they may work for some patients, may not work for the others; in addition, side effects may be present for some patients with the need to decrease dosage to not optimal levels. Furthermore, the indications of these drugs are for other neuropathic pain disorders and currently there is no medication specifically indicated for the management of TNP based on its molecular pathophysiology. The calcitonin gene‐related peptide (CGRP) is a key neuropeptide involved in migraine pathophysiology. There is evidence showing that CGRP has a role in other disorders mediated by the trigeminal system in addition to migraine; CGRP has shown to have a role in orofacial pain such as in TMD and in trigeminal neuropathic pain. Erenumab‐aooe is the first antibody therapeutic targeting the CGRP receptor with FDA approval for migraine prevention that is well tolerated and with a good safety profile. Therefore, the scientific premise for this study is that inhibiting the CGRP pathway in trigeminal neuropathic pain will decrease pain and pain related outcomes in a safe and well tolerated manner for this patient population. Potential participants will be pre‐screened at the Brotman Facial Pain clinic, at the Oral and Maxillofacial Surgery Clinic both at the University of Maryland, School of Dentistry, at the Pain Medicine Clinic at the University of Maryland, School of Medicine or by telephone; those willing to participate will be scheduled for a screening and baseline visit (Visit 0). During this visit, potential participants will be evaluated for eligibility for trigeminal neuropathic pain (subjects with diagnosis based on the International classification of headache disorders ICHD‐3 and International classification of Orofacial Pains ICOP of idiopathic trigeminal neuralgia with concomitant continuous pain, painful posttraumatic trigeminal neuropathy or idiopathic painful trigeminal neuropathy) and written informed consent will be obtained. The screening and baseline procedures include medical history review, clinical examinations, tests and administration of questionnaires. Instructions will be given for the completion of a Daily Symptom Diary (DSD) and other questionnaires at home or online. Participants who show compliance with 80 % completion of the DSD and who meet the pain score (inclusion criteria) for 4 weeks/28 days during the baseline period from Visit 0, will be randomly assigned to one of two groups either the investigational drug or placebo and will be scheduled for Visit 1. The study drug is Erenumab 140 mg, SC injection. Participants will attend 6 clinic visits (Visit 0‐Visit 5). After randomization and on Visit 1, the participant will receive the drug or placebo. This same treatment will be administered once a month for 3 months (3 cycles/12weeks).

BACKGROUND:

To date, it remains challenging for clinicians to make informed decisions about which dosage of erenumab is more effective for treating adult patients with migraine. Thus, we sought to examine the safety and efficacy of different doses of erenumab in this group of patients.

METHODS:

We searched several databases from inception to May 31, 2021, irrespective of language. We included only RCTs that compared erenumab 70 mg, erenumab 140 mg, and placebo in migraine patients. The primary efficacy outcome was change in monthly migraine days (MMDs). The primary safety outcome was defined as treatment-emergent adverse events (TEAEs). We reported relative risks (RRs) with 95% credible intervals (CrIs) from the analysis.

RESULTS:

Overall, eight trials comprising 4281 participants were included in this study. Network meta-analysis showed that both erenumab 70 mg (MD: - 1.43, 95% CrI: - 1.71 to - 1.16) and erenumab 140 mg (MD: - 1.78, 95% CrI: - 2.21 to - 1.45) were associated with decreased MMDs. Also, erenumab 140 mg was associated with significantly lower MMDs than erenumab 70 mg (MD: - 0.34, 95% CrI: - 0.68 to - 0.01). In terms of primary safety outcome, neither erenumab 70 mg (RR: 0.98, 95% CrI: 0.92 to 1.05) nor erenumab 140 mg (RR: 0.99, 95% CrI: 0.91 to 1.07) was associated with increased risk of TEAEs.

CONCLUSIONS:

The results from this study suggested erenumab 140 mg might provide better efficacy than 70 mg among adult patients with migraine, without increasing TEAEs. Future elaborated RCTs with a larger number of participants are warranted to validate these discoveries.

Erenumab (Aimovig®, erenumab-aooe), a fully human monoclonal antibody (MAb) calcitonin gene-related peptide (CGRP) receptor antagonist, is the first MAb approved for the prophylaxis of migraine in adults. Erenumab is subcutaneously administered and has a convenient once-monthly/every-4-week dosing regimen. In patients with episodic or chronic migraine, erenumab is effective and generally well tolerated, significantly reducing the frequency of migraines and the use of migraine-specific medications during weeks 9–12 and months 4–6 relative to placebo. Erenumab also displays efficacy in numerous subgroup analyses, including in patients with episodic or chronic migraine with prior prophylactic treatment failure and/or patients with a history of aura. Although the efficacy and tolerability profiles of erenumab remain to be determined in specific populations (for example, in patients with major cardiovascular disease), it is a promising candidate for alleviating the widespread personal, societal and economic burdens that are presently associated with migraine.

Researchers are trying to determine if there is a difference between brain images of subjects that do respond to treatment with erenumab and subjects who do not respond to treatment with erenumab using Magnetic Resonance Imaging (MRI).

To explore the relationship between clinical response to erenumab and genetic biomarkers

The investigators will evaluate the efficacy for use of intravenous erenumab 140mg for treatment of status migrainosus in an open-label, pilot study.

The preventive treatment for cluster headache is often limited by a lack of efficacy or side effects. Calcitonin gene-related peptide (CGRP) has been implicated in the pathophysiology of cluster headache. Galcanezumab, a monoclonal antibody against calcitonin gene-related peptide (CGRP), significantly reduced the frequency of episodic cluster headache attacks. We report the case of a 38-year-old woman with chronic refractory cluster headache and comorbid migraine who received erenumab in 4 repeated doses of 70 mg subcutaneously over 25 weeks. Attack frequency decreased from three attacks per day to several attacks per week. Erenumab seemed to be highly effective in the prevention of cluster headache attacks in this patient. We suggest that randomized control trials should be performed.