Novel synthetic treatment options for migraine

ABSTRACT

Introduction: Migraine is one of the most common neurological disorders. Nowadays, the 5-HT_1B/1D receptor agonists, namely triptans, are considered as the standard of care for migraine acute treatment. However, triptans have limitations in some patients, such as incomplete pain relief, headache recurrence, and cardiovascular contraindications. New 5-HT_1F receptor agonists, namely ditans, and calcitonin gene-related peptide receptor antagonists, namely gepants, have been developed as migraine-specific treatments.

Areas covered: This paper reviews the available data from RCTs to assess the clinical efficacy, safety, and tolerability profile of lasmiditan, rimegepant, and ubrogepant for the acute treatment of migraine and atogepant for the prevention of migraine.

Expert opinion: Available data suggest that lasmiditan, rimegepant, and ubrogepant might not have a clinical efficacy similar to triptans. Lasmiditan did not cause the typical triptan side effects but was associated with central nervous system side effects, causing temporary driving impairment. On the contrary, the new generation of gepants showed a placebo-like tolerability profile and the absence of a specific pattern of side effects. Future studies on lasmiditan and gepants with respect to established effective comparators are mandatory to support phase III results and to help clinicians to balance the benefit/risk profiles of the various acute and preventive medications.

KEYWORDS:

• Acute treatment
• atogepant
• ditans
• gepants
• lasmiditan
• preventive treatment
• rimegepant
• ubrogepant

Article highlights

• Migraine is the leading cause of years of life lived with disabilities in under 50s in both genders.

• The pharmacological treatment of migraine involves the use of abortive medications and preventative medications.

• The 5-HT_1B/1D receptor agonists, namely triptans, are the gold standard for migraine acute treatment but have class contraindications that limit their use in patients with cardiovascular diseases.

• Lasmitidan, the first compound of ditans class, presents an acute antimigraine activity via 5-HT_1F receptor agonism without vasoconstrictive action.

• Lasmitidan showed to be superior to placebo in acute migraine treatment, but patients are not allowed to drive for 8 h after its intake according to prescribing information.

• Gepants present an antimigraine activity via calcitonin gene-related peptide receptor antagonism and the second generation of molecules does not cause hepatoxicity based on available clinical trial data and real-world surveillance.

• Rimegepant and ubrogepant showed to be superior to placebo in acute migraine treatment and atogepant showed to be superior to placebo in migraine prevention.

• Future studies on lasmiditan and gepants with respect to established effective comparators are needed to help clinicians to balance the benefit/risk profiles of the various acute and preventive medications.

This box summarizes key points contained in the article.

Declaration of interest

A Negro has received speaking honoraria and has served on the advisory boards of Allergan, Eli Lilly and Company and Novartis. P Martelletti has meanwhile received speaker’s honoraria and has served on the advisory boards of Allergan, Eli Lilly and Company, Novartis and Teva Pharmaceuticals. He is also an EMA Expert and has served as Editor in Chief for The Journal of Headache and Pain and as Editor in Chief for Springer Nature Comprehensive Clinical Medicine. He also declares received royalties from Springer Nature.

Reviewer disclosures

One referee has served as a consultant for Eli Lilly and Company, Amgen Inc, BioHaven, and Allergan. They also have served as a Data and Safety Monitoring Board Member for Allergan. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This manuscript has not been funded.