Gepants

BACKGROUND: Triptans are effective for many migraine patients, but some do not experience adequate efficacy and tolerability. The European Headache Federation (EHF) has proposed that patients with lack of efficacy and/or tolerability of ≥ 2 triptans ('triptan resistance') could be considered eligible for treatment with the novel medications from the ditan and gepant groups. There is little data on the frequency of 'triptan resistance'. METHODS: We used patient self-report data from the German Migraine and Headache Society (DMKG) Headache Registry to assess triptan response and triptan efficacy and/or tolerability failure...

INTRODUCTION: Migraine is a common debilitating neurological disorder affecting a large proportion of the general population. Calcitonin gene-related peptide (CGRP), a 37-amino acid neuropeptide, plays a key role in the pathophysiology of migraine, and the development of therapies targeting the anti-CGRP pathway has revolutionized the field of migraine treatment. METHODS: An expert task force of neurologists in the United Arab Emirates (UAE) developed and critically assessed recommendations on the use of CGRP-based therapies in migraine treatment and management in the UAE, based on available published literature...

Targeting CGRP has proved to be efficacious, tolerable, and safe to treat migraine; however, many patients with migraine do not benefit from drugs that antagonize the CGRPergic system. Therefore, this review focuses on summarizing the general pharmacology of the different types of treatments currently available, which target directly or indirectly the CGRP receptor or its ligand. Moreover, the latest evidence regarding the selectivity and site of action of CGRP small molecule antagonists (gepants) and monoclonal antibodies is critically discussed...

After 35 years since the introduction of the International Classification of Headache Disorders (ICHD), we are living in the era of the second great revolution in migraine therapies. First, discoveries of triptans provided a breakthrough in acute migraine treatment utilizing bench-to-bedside research results on the role of serotonin in migraine. Next, the discovery of the role of neuropeptides, more specifically calcitonin gene-related peptide (CGRP) in migraine attack led to the development of anti-CGRP therapies that are effective both in acute and preventive treatment, and are also able to reduce migraine-related burden...

PURPOSE OF REVIEW: Despite the unmet therapeutic needs of patients with chronic migraine (CM) and/or medication overuse, available treatment options are limited. Recently, four calcitonin gene-related peptide receptor antagonists, known as gepants, have been approved for the treatment of migraine. This review focuses on the preventive treatment of CM with gepants and highlights recent findings. RECENT FINDINGS: Two randomized controlled trials (RCTs) have shown promising results for rimegepant and atogepant as preventive treatments for CM...

Multiple drugs targeting the calcitonin gene-related peptide (CGRP) receptor have been developed for the treatment of migraine. Here, the effect of the small-molecule CGRP receptor antagonist zavegepant (0.1 nM-1 µM) on CGRP-induced relaxation in isolated human coronary arteries (HCAs) was investigated. A Schild plot was constructed and a pA2 value was calculated to determine the potency of zavegepant. The potency and Schild plot slopes of atogepant, olcegepant, rimegepant, telcagepant, ubrogepant and zavegepant in HCAs and human middle meningeal arteries (HMMAs), obtained from our earlier studies, were compared...

OBJECTIVE: To characterize migraine pathophysiology, presentation, and current treatment strategies, specifically in regard to vestibulocochlear manifestations of migraine. METHODS: Narrative review of available literature. RESULTS: Migraine disorder can be described as a spectrum of otologic manifestations, with vestibular migraine now recognized with fully-fledged diagnostic criteria. Otologic manifestations are theorized to be due, in part, to trigeminal innervation of the inner ear structures and calcitonin gene-related peptide (CGRP) expression within the labyrinth...

Migraine is common in children and adolescents and can cause significant disability. There are relatively limited evidence-based treatment options available, especially when compared with treatment of migraine in adults. The Pediatric Research Equity Act requires the study of a new drug or biologic in pediatric populations. As such it is mandatory that the newest migraine treatment options available for adults be evaluated in children and adolescents. It will take years before results from clinical trials in pediatric patients become available...

Drugs that act on the calcitonin gene-related peptide (CGRP) pathway herald the dawn of a new era in the management of migraine headaches. The blockade of CGRP alleviates neural inflammation and has been associated with reduced pain sensitization. Zavegepant is a third-generation drug and is the first intranasal CGRP antagonist to be developed. This systematic review aims to assess the safety, efficacy, pharmacokinetics, and tolerability of Zavegepant as an abortive treatment for migraine. Studies that assessed the safety, tolerability, and efficacy of Zavegepant for migraine were identified through a systematic literature review of PubMed, Clinicaltrials...

Migraine is a debilitating neurological condition affecting millions of people worldwide. Until a few years ago, preventive migraine treatments were based on molecules with pleiotropic targets, developed for other indications, and discovered by serendipity to be effective in migraine prevention, although often burdened by tolerability issues leading to low adherence. However, the progresses in unravelling the migraine pathophysiology allowed identifying novel putative targets as calcitonin gene-related peptide (CGRP)...

Advancements in molecular biology and neuroscience have uncovered calcitonin gene-related peptide (CGRP), a neuropeptide consisting of thirty-seven amino acids that plays a crucial role in migraine pathogenesis. CGRP receptor antagonist or gepant is an oral medication that can impede the nociceptive signaling pathway related to CGRP. Atogepant, the latest CGRP antagonist approved by the Food and Drug Administration (FDA) for prophylaxis of episodic migraine, works by non-competitively blocking CGRP receptors, thereby curtailing neurogenic inflammation and pain sensitization...

PURPOSE OF REVIEW: This review examines recent evidence and applies bioethical principles to evaluate the benefits and risks of using step therapy in the treatment of migraine. RECENT FINDINGS: With the CGRP mAbs, gepants, and lasmiditan now on the market for up to 5 years, new research, including network meta-analyses and long-term use studies, can evaluate the comparative efficacy, tolerability, and adherence of these medications relative to older acute and preventive medications for the treatment of migraine...

PURPOSE OF REVIEW: Gepants are small molecules that antagonize calcitonin gene-related peptide (CGRP) receptors. Due to their favorable side effect profile and versatility in treating headaches acutely and preventively, gepants are preferred over triptans. We will cover the indications for the four FDA-approved gepants in adults: rimegepant, atogepant, ubrogepant, and zavegepant. This review will illustrate how gepants will continue to revolutionize the acute and preventive treatment of headaches...

The monoclonal antibodies (mAbs) blocking the calcitonin-gene related peptide (CGRP) pathway, collectively called here "anti-CGRP/rec mAbs", have dramatically improved preventive migraine treatment. Although their efficacy and tolerability were proven in a number of randomized controlled trials (RCTs) and, maybe even more convincingly, in real world settings, a number of open questions remain. In this narrative review, we will analyze published data allowing insight in some of the uncertainties related to the use of anti-CGRP/rec mAbs in clinical practice: their differential efficacy in migraine subtypes, outcome predictors, switching between molecules, use in children and adolescents, long-term treatment adherence and persistence, effect persistence after discontinuation, combined treatment with botulinum toxin or gepants, added-value and cost effectiveness, effectiveness in other headache types, and potential contraindications based on known physiological effects of CGRP...

Migraine is a leading cause of disability worldwide, and acute migraine attacks are a common reason for patients to seek care in the emergency department (ED). There have been recent advancements in the care of patients with migraine, specifically emerging evidence for nerve blocks and new pharmacological classes of medications like gepants and ditans. This article serves as a comprehensive review of migraine in the ED, including diagnosis and management of acute complications of migraine (eg, status migrainosus, migrainous infarct, persistent aura without infarction, and aura-triggered seizure) and use of evidence-based migraine-specific treatments in the ED...

BACKGROUND: Rimegepant is an oral, small molecule calcitonin gene-related peptide receptor antagonist for acute treatment of migraine and migraine prevention. METHODS: This was a single-site, placebo-controlled, sequential, single and multiple ascending dose study in healthy males and females, aged 18-55 years, with no clinically significant medical history. The objectives were to assess the safety, tolerability, and pharmacokinetics of the oral capsule free-base formulation...

OBJECTIVE: While there are several trials that support the efficacy of various drugs for migraine prophylaxis against placebo, there is limited evidence addressing the comparative safety and efficacy of these drugs. We conducted a systematic review and network meta-analysis to facilitate comparison between drugs for migraine prophylaxis. METHODS: We searched MEDLINE, EMBASE, CENTRAL, and clinicaltrials.gov from inception to August 13, 2022, for randomized trials of pharmacological treatments for migraine prophylaxis in adults...

INTRODUCTION: Migraine is a leading cause of years lived with disability and preventive strategies represent a mainstay to reduce health-related disability and improve quality of life of migraine patients. Until a few years ago, migraine prevention was based on drugs developed for other clinical indications and relocated in the migraine therapeutic armamentarium, characterized by unfavorable tolerability profiles. The advent of monoclonal antibodies against Calcitonin Gene-Related Peptide (CGRP) and gepants, CGRP receptor antagonists, has been a turning point in migraine prevention owing to advantageous efficacy, safety and tolerability profiles...

INTRODUCTION: Migraine is a prevalent neurological condition characterised by disabling headache attacks. In recent decades, new drugs have been developed specifically for the acute and preventive treatment of migraine based on its pathophysiology. These include calcitonin gene-related peptide (CGRP) antagonists (CGRP) (gepants) and selective serotoninergic 5-HT1F receptor agonists (ditans). CGRP is a neuropeptide released by trigeminal terminals that acts as a vasodilator, causes neurogenic inflammation and thus generates pain and sensitisation in migraine...

Rimegepant is a small-molecule calcitonin gene-related peptide receptor antagonist (gepant) with demonstrated efficacy and safety in the acute and preventive treatment of migraine. Here, we report the pharmacokinetics and safety of a single 75-mg oral dose of rimegepant in subjects with severe, moderate, or mild hepatic impairment and matched healthy subjects from an open-label, single-dose, 4-group phase 1 study. Thirty-six subjects aged 41-71 years were enrolled, including 6 each with severe, moderate, or mild hepatic impairment and 18 healthy subjects...