Gepants

Small molecule calcitonin gene-related peptide (CGRP) receptor antagonists are commonly referred to as gepants. The first generation of gepants provided the first line of evidence of CGRP-mediated antimigraine medication in 2004-2011. However, further development was halted due to either lack of oral availability or concerns of hepatotoxicity. More than 15 years later, the first second generation of gepants, ubrogepant and rimegepant, are now approved for the acute treatment of migraine with or without aura...

Menstrually related migraine is a disabling condition affecting 35% to 54% females with migraine during their fertile years. The International Headache Classification distinguishes menstrually related migraine from pure menstrual migraine based on the occurrence of the attacks even outside the perimenstrual periods. Hormonal fluctuations are the main driver for the disease in subjects with genetic susceptibility and alterations of brain structures and connectivity. Menstrually related attacks are often particularly severe and disabling requiring proper management...

Symptomatic treatment of migraine includes patient education, mainly to avoid medication overuse and known trigger factors, as well as pharmaceutical and nonpharmaceutical interventions. Disease-specific and mechanism-based agents include ergotamine and dihydroergotamine targeting the adrenergic, dopaminergic, and serotoninergic systems followed by triptans, specific agonists for 5-HT1B/1D/1F receptors, the latest being more favorable in terms of safety and documentation of efficacy. Recently, antagonists of calcitonin gene-related peptide (gepants) and selective agonists of the 5-HT1F receptor (ditans) have been added, with promising efficacy and safety...

Migraine is a prevalent and disabling neurological disease. Its preventive treatment for decades has been rather limited due to the absence of disease-specific therapies with limited efficacy and tolerability. The advances made in migraine research have led to the discovery of the calcitonin gene-related peptide (CGRP) and its role in migraine pathophysiology. CGRP is a neuropeptide that acts as potent vasodilator and is involved in pain processing. Increased levels of plasma CGRP have been observed during migraine attacks as well as interictally when comparing patients with migraine and healthy controls...

Since the discovery of calcitonin gene-related peptide (CGRP) in 1982, its integral role in migraine pathophysiology, specifically migraine pain, has been demonstrated through cumulative scientific discoveries that have led to the development and approval of migraine-specific therapeutics. Today, eight drugs, including monoclonal antibodies and small molecule CGRP receptor antagonists, known as gepants, have received approval for acute or preventive treatment of migraine. The primary mechanism of these drugs is to block CGRP signaling, thus preventing CGRP-mediated nociception and neurogenic inflammation...

In recent years, the treatment of migraine has experienced a breakthrough in the development of drugs that target the calcitonin gene-related peptide (CGRP) signaling pathway. Monoclonal antibodies against the receptor or ligand have been developed for the preventive treatment of migraine; whereas, orally administered small molecule CGRP receptor antagonists, called gepants, have been developed for both acute and/or preventive treatment. Both modalities have demonstrated safe and effective treatment of migraine, reducing the number of migraine days for patients as well as reducing symptoms and improving patient function and overall quality of life...

The study of migraine is based on the complexity of the pathology, both at the pathophysiological and epidemiological levels. Although it affects more than a billion people worldwide, it is often underestimated and underreported by patients. Migraine must not be confused with a simple headache; it is a serious and disabling disease that causes considerable limitations in the daily life of afflicted people, including social, work, and emotional effects. Therefore, it causes a daily state of suffering and discomfort...

INTRODUCTION: Migraine, characterized by recurrent headaches and often accompanied by other symptoms like nausea, vomiting, and sensitivity to light and sound, significantly impacts patients' quality of life (QoL) and daily functioning. The global burden of migraines is reflected not only in terms of reduced QoL but also in the form of increased healthcare costs and missed work or school days. While UAE (United Arab Emirates)-specific consensus-based recommendations for the effective use of preventive calcitonin gene-related peptide (CGRP)-based migraine therapies have been published previously, an absence of such regional guidance on the management of acute migraine represents a gap that needs to be urgently addressed...

Treatment of migraine attacks is advised in all patients, using non-steroidal anti-inflammatory drugs when the pain is mild and triptans when the pain intensity is moderate-severe. However, the effectiveness of these drugs is moderate, a high percentage of patients have side effects, and triptans are contraindicated in people with a history of stroke, ischaemic heart disease or poorly controlled hypertension. Hence, there is an urgent need for new therapeutic alternatives. In recent years, new drugs for migraine attacks have become available, most notably ditans (lasmiditan) and gepants (ubrogepant and rimegepant)...

INTRODUCTION: Migraine as headache attacks with autonomic symptoms is a serious condition and it is important to treat a single attack effectively in order to improve not only the patient's quality of life at a given moment but also to prevent the migraine from becoming a chronic one. AREA COVERED: The article briefly presents the guidance in selecting the most appropriate pharmacological treatment of migraine attack, indicating a personalized approach to migraine patient...

Migraine is one of the most prevalent and disabling diseases in the world. Migraine attack treatments and prophylactic treatments of this disease are essential to lessen its individual, social, and economic impact. This is a narrative review of the main drugs used for treating migraine, as well as the experimental models and the theoretical frameworks that led to their development. Ergot derivatives, triptans, non-steroid anti-inflammatory drugs, tricyclic antidepressants, beta-blockers,: flunarizine,: valproic acid,: topiramate, onabotulinumtoxin A, ditans, monoclonal antibodies against CGRP and its receptor, and gepants are discussed...

No abstract text is available yet for this article.

In this editorial we aim to provide potential therapeutic options in patients who do not benefit from treatment with CGRP(r) monoclonal antibodies. Based on current real-life studies and analysis of practical and economic aspects, we will analyze the potential benefits of changing CGRP-targeted treatment.

BACKGROUND AND OBJECTIVES: Many acute treatment options exist for migraine. However, large-scale, head-to-head comparisons of treatment effectiveness from real-world patient experience reports are lacking. METHODS: This is a retrospective analysis of 10,842,795 migraine attack records extracted from an e-diary smartphone application between June 30, 2014, and July 2, 2020. We analyzed 25 acute medications among 7 classes-acetaminophen, nonsteroid anti-inflammatory drugs (NSAIDs), triptans, combination analgesics, ergots, antiemetics, and opioids...

INTRODUCTION: Significant advances in migraine research have contributed to the development of new drugs for the treatment of migraine. Monoclonal antibodies (mAbs) against Calcitonin Gene-Related Peptide (CGRP) or its receptor and CGRP receptor antagonists (gepants) have been associated with a good safety profile and resulted in an overall efficacy in reducing the number of monthly migraine days both in episodic and chronic forms of migraine. AREAS COVERED: The results from main investigation studies (phase 2 or 3) of CGRP-targeting drugs (both anti-CGRP mAbs and gepants) are reported in this expert-opinion review...

INTRODUCTION: There have been no prior trials directly comparing the efficacy of different calcitonin gene-related peptide (CGRP) antagonists for migraine prevention. Reported are the results from the first head-to-head study of two CGRP antagonists, galcanezumab (monoclonal antibody) versus rimegepant (gepant), for the prevention of episodic migraine. METHODS: In this 3-month, double-blind, double-dummy study, participants were randomized (1:1) to subcutaneous (SC) galcanezumab 120 mg per month (after a 240 mg loading dose) and a placebo oral disintegrating tablet (ODT) every other day (q...

Migraine represents the most common neurologic disorder, ranking second among the world's causes of disability [expressed as years lived with disability (YLDs)]. Patients often do not receive the best therapy because of safety issues, tolerance, and prescription accessibility. General practitioners are not always educated about the disease, and specialists are few and often difficult to reach. Therapies are limited and have many side effects that can impede the prescription. Prophylactic therapy is recommended in case of four or more headaches a month, eight or more headache days a month, debilitating headaches, and medication-overuse headaches...

No abstract text is available yet for this article.

INTRODUCTION: Migraine pharmacological therapies targeting calcitonin gene-related peptide (CGRP), including monoclonal antibodies and gepants, have shown clinical effect and optimal tolerability. Interactions between treatments of COVID-19 and CGRP-related drugs have not been reviewed. AREAS COVERED: An overview of CGRP, a description of the characteristics of each CGRP-related drug and its response predictors, COVID-19 and its treatment, the interactions between CGRP-related drugs and COVID-19 treatment, COVID-19 and vaccination-induced headache, and the neurological consequences of Covid-19...

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...