Place of next generation acute migraine specific treatments among triptans, non-responders and contraindications to triptans and possible combination therapies

Abstract

Background: For many years triptans have been the cornerstone of acute migraine treatment. Nevertheless, treatment with triptans may not always be initiated due to contraindications (seen in approximately one fifth of patients) or inadequate response (seen in approximately one third of patients). New acute therapies, including 5-hydroxytryptamine (5-HT)1F receptor agonists, also known as ditans (lasmiditan) and small molecule antagonists of the calcitonin gene-related peptide receptor, also known as gepants (rimegepant and ubrogepant), may be an effective alternative. Methods: We searched Pubmed for keywords, summarized the literature and provided a comprehensive review on the place of next generation acute migraine specific treatments among triptans. Results and conclusion: Post-hoc analyses reported no differences in efficacy of gepants/ditans between responders and non-responders to triptans, but research is hampered by lack of consensus on the definition of non-responder. Due to (partially) overlapping mechanisms of action, it remains unknown whether combination therapy with lasmiditan, gepants and triptans will have added value over monotherapy. Preclinical studies and post-hoc analyses cautiously indicate that these new drugs are safe for patients with cardiovascular risk factors. However, long-term studies are needed to prove cardiovascular safety. The risk of developing medication overuse headache may differ between triptans, ditans and gepants, but further studies are needed to confirm this difference. Head-to-head randomized controlled trials of acute therapies and combinations of therapies are needed to determine their place in migraine treatment among established therapies.

Efficacy, safety and indirect comparisons of lasmiditan, rimegepant, and ubrogepant for the acute treatment of migraine: A systematic review and network meta-analysis of the literature

“…Further, study populations tended to be very homogeneous, as most studies excluded either non-responders, patients with medication overuse or patients with chronic migraine, limiting their generalizability. Some of these aspects are investigated with more detail in other papers within this Special Collection (37,38). Moreover, placebo response rate variations for two-hour pain free outcomes vary by nearly two-fold, which offers caution in terms of consistency of effect as a key assumption in network meta-analysis (39).…”

New migraine drugs

“…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).…”

Neues bei Kopfschmerzen 2022–2023

“…Post-hoc-Analysen ergaben keine Unterschiede in der Wirksamkeit von Gepanten und Lasmiditan bei Personen, bei denen Triptane nicht oder nicht ausreichend wirksam waren [20], d. h. die neuen Substanzen könnten für Patienten eine Therapieoption darstellen, die bisher nur unzureichend behandelt werden konnten. Die Interpretation der Ergebnisse ist schwierig, da es keinen Konsens über die Definition von Non-Respondern gibt [21].…”