Abstract
New drugs for the acute treatment of migraine attacks and for migraine prevention: A special issue of Cephalalgia
In some patients, triptans are not effective for the acute treatment of migraine attacks or are contraindicated due to concomitant vascular diseases. For these patients, there was a need to develop new substances for the acute treatment of migraine, which can be used specifically for patients with contraindications to triptans, as they do not have vasoconstrictive properties.
Patients with frequent and severe migraine attacks require a preventive treatment. Until a few years ago, migraine prevention included substances originally developed for other indications, such as the beta-blockers, flunarizine, valproic acid, topiramate, and amitriptyline. OnabotulinumtoxinA, which is indicated for the prevention of chronic migraine, was originally developed for the treatment of focal dystonia. Most oral preventive drugs induce a 50% reduction of monthly migraine days in a percentage of patients that varies between 30% and 50%. The main problem with traditional oral migraine prophylactics has been adverse drug reactions, which have led to discontinuation of therapy in 10% to 40% of patients within the first six to 12 months.
In recent years, there have been spectacular advances in the development of specific drugs for the acute treatment of migraine attacks and for migraine prevention. One approach is monoclonal humanized or fully human antibodies against the polypeptide CGRP or the CGRP-receptor. Another approach is antagonists at the CGRP receptor itself such as rimegepant and atogepant.
There has also been progress in the acute therapy of migraine especially for patients who have contraindication to triptans. New drugs for the acute treatment of migraine include the 5HT1F-agonist lasmiditan (belonging to the “ditans” family) and the CGRP receptor blockers rimegepant and ubrogepant (so called “gepants”).
All publications on phase II and phase III studies of the new migraine preventive drugs, as well as of gepants and ditans, respectively, were written with the support of pharmaceutical companies. This also applies to secondary analyses and subgroup analyses. Naturally, there is a conscious or unconscious bias in the presentation of study results in these publications.
The International Headache Society has therefore decided to present the current state of knowledge on the new migraine drugs in a special issue of Cephalalgia. To ensure this is as uninfluenced as possible, two or more members of the junior headache research group with no or minimal conflicts of interest were selected for each of the reviews. The author group was supplemented by an experienced senior author and, when required, by a statistician. The International Headache Society deems, therefore, that the composition of the author groups will provide a presentation of the efficacy and potential side effects or safety aspects of the new drugs for the treatment of acute migraine attacks and for the prevention of migraine that is as objective as possible and can be used for clinical practice. In addition to meta-analyses of efficacy and tolerability or safety for both acute and preventive medications (1–3), some of the publications address practical aspects of use, such as migraine prevention in patients with medication overuse or medication overuse headache (4), the results of open-label long-term studies for both drugs for acute therapy (5) and for migraine prophylaxis (6), and other aspects such as nonresponders to previous therapies, combination therapy switching, and termination of therapy (7,8).
