Efficacy of rimegepant for the acute treatment of migraine based on triptan treatment experience: Pooled results from three phase 3 randomized clinical trials.

Background: This post-hoc analysis from three phase 3 treatment trials of rimegepant 75 mg - an oral small molecule calcitonin gene-related peptide receptor antagonist for acute and preventive treatment of migraine - assessed efficacy in adults with migraine based on triptan treatment experience.

Methods: Participants were assigned to one of four groups based on triptan treatment experience: insufficient response (e.g.

Once-daily oral atogepant for the long-term preventive treatment of migraine: Findings from a multicenter, randomized, open-label, phase 3 trial.

Objective: To assess long-term safety, tolerability, and efficacy of once-daily oral atogepant 60 mg in adults with migraine.

Background: Atogepant is an oral, small-molecule, calcitonin gene-related peptide receptor antagonist approved for the preventive treatment of episodic migraine.

Methods: A 52-week, multicenter, randomized, open-label trial of adults (18-80 years) with migraine.

Phase Ib, open-label, fixed-sequence, drug-drug interaction, safety, and tolerability study between atogepant and ubrogepant in participants with a history of migraine.

Objective: To evaluate potential drug-drug interactions of ubrogepant and atogepant.

Background: Ubrogepant and atogepant, calcitonin gene-related peptide (CGRP) receptor antagonists, are recently approved drugs for acute and preventive treatment of migraine, respectively. For patients with migraine who are prescribed atogepant for the preventive treatment of migraine, health care providers could prescribe ubrogepant for the acute treatment of breakthrough migraine attacks.

Effect of Atogepant for Preventive Migraine Treatment on Patient-Reported Outcomes in the Randomized, Double-blind, Phase 3 ADVANCE Trial.

Background And Objectives: The oral calcitonin gene-related peptide receptor antagonist atogepant is indicated for the preventive treatment of episodic migraine. We evaluated changes in patient-reported outcomes with atogepant in adults with migraine.

Methods: In this phase 3, 12-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group trial (ADVANCE), adults with 4-14 migraine days per month received atogepant (10, 30, or 60 mg) once daily or placebo.

Adverse Events Reported with Therapies Targeting the CGRP Pathway During the First 6 Months Post-launch: A Retrospective Analysis Using the FDA Adverse Events Reporting System.

Introduction: Through 2018, three calcitonin gene-related peptide pathway-targeted monoclonal antibodies (CGRP mAbs) had received US Food and Drug Administration (FDA) approval for migraine prevention: erenumab, fremanezumab, and galcanezumab.

Methods: This retrospective analysis evaluated adverse events (AEs) spontaneously reported to the FDA Adverse Event Reporting System (FAERS) safety surveillance database during the first 6 months post-approval of erenumab (May 2018 to November 2018), fremanezumab (September 2018 to March 2019), and galcanezumab (September 2018 to March 2019). Reporting rates (RR) per 1000 exposed patients were calculated from number of reported events (when product classified as "primary suspect") in each AE category and estimated number of treated patients based on de-identified prescription data (IQVIA database) and were ranked on the basis of frequency for each product.

Post hoc analysis of clinical trial data and pharmacokinetic data to assess wearing-off of erenumab within monthly treatment cycle.

Background: Treatment wearing-off has been reported for calcitonin gene-related peptide-pathway monoclonal antibodies, including erenumab, specifically in the last week of the monthly dosing cycle.

Objective: We sought to determine the consistency of erenumab effect throughout the monthly treatment cycle.

Methods: In this post hoc analysis of four pivotal double-blind, randomized controlled studies of erenumab in episodic and chronic migraine, we assessed wearing-off based on change in weekly migraine days at week 4 versus average over weeks 1-3 in each monthly dosing cycle.

The importance of an early onset of migraine prevention: an evidence-based, hypothesis-driven scoping literature review.

Recently approved migraine preventive therapies facilitate rapid control of migraine activity, potentially improving patients' lives and minimizing the societal burden of migraine. This review synthesizes available evidence on rates and timing of early onset of migraine prevention and identifies patient-level outcomes related to early onset prevention. This evidence-based scoping review identified all available clinical trial evidence regarding the early onset of prevention of migraine, under the hypothesis '.

Likelihood of response with subsequent dosing for patients with migraine and initial suboptimal response with eptinezumab: A post hoc analysis of two placebo-controlled randomized clinical trials.

Objective: To develop a multivariable model assessing factors predicting a second-dose response to eptinezumab treatment over weeks 13-24 in patients with migraine initially reporting a suboptimal response over weeks 1-12.

Background: Eptinezumab is a monoclonal antibody used for migraine prevention, administered every 12 weeks. In the PROMISE-1 and PROMISE-2 studies, the first-dose response to eptinezumab treatment (≥50% monthly migraine day [MMD] reduction over weeks 1-12) occurred in ~50-60% of patients with episodic (EM) and chronic migraine (CM), respectively.

Practical Insights on the Identification and Management of Patients with Chronic Migraine.

Chronic migraine (CM) is one of the most disabling diseases, and it is commonly misdiagnosed and mistreated. Despite the importance of a timely and accurate diagnosis for the effective management of CM, recent surveys have shown that only 20-25% of individuals with CM receive a correct diagnosis. The obvious consequences of misdiagnosed CM are prolongation of symptoms and their associated effects on disability and health-related quality of life.

Does "wearing off" of efficacy occur in galcanezumab-treated patients at the end of the monthly treatment cycle? Post hoc analyses of four phase III randomized trials.

Objective: The purpose of this study was to propose a definition of "wearing off" at the individual patient-level and determine the percentage of patients with migraine who experience "wearing off" of efficacy of galcanezumab at the end of a treatment cycle using this predefined threshold.

Background: Anecdotal reports suggest that some patients may experience "wearing off" of efficacy during the last week of their calcitonin gene-related peptide monoclonal antibody treatment cycle. A previous post hoc analysis of galcanezumab demonstrated consistent efficacy at each week throughout all monthly dosing intervals at the population-level, but "wearing off" has not been assessed at the individual patient-level.

Ubrogepant Is Safe and Efficacious in Participants Taking Concomitant Preventive Medication for Migraine: A Pooled Analysis of Phase 3 Trials.

Introduction: Ubrogepant is a calcitonin gene-related peptide receptor antagonist indicated for acute treatment of migraine that can be used to treat breakthrough attacks in individuals taking preventive treatment for migraine. We evaluated the impact of preventive medication use on the efficacy and safety of ubrogepant for the acute treatment of migraine.

Methods: This was an analysis of pooled efficacy data from the ACHIEVE I and ACHIEVE II phase 3 trials, in which efficacy of ubrogepant was assessed at 2 h after taking study medication for pain freedom, absence of most bothersome symptom (MBS), and pain relief.

Hypervigilance, Allostatic Load, and Migraine Prevention: Antibodies to CGRP or Receptor.

Migraine involves brain hypersensitivity with episodic dysfunction triggered by behavioral or physiological stressors. During an acute migraine attack the trigeminal nerve is activated (peripheral sensitization). This leads to central sensitization with activation of the central pathways including the trigeminal nucleus caudalis, the trigemino-thalamic tract, and the thalamus.

Real-World Evidence for Control of Chronic Migraine Patients Receiving CGRP Monoclonal Antibody Therapy Added to OnabotulinumtoxinA: A Retrospective Chart Review.

Introduction: Combination use of onabotulinumtoxinA and calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) has the potential to be more effective than either therapy alone for migraine prevention.

Methods: This retrospective, longitudinal chart review included adults with chronic migraine treated at one clinical site with ≥ 2 consecutive cycles of onabotulinumtoxinA and ≥ 1 month of subsequent combination treatment with CGRP mAbs. Charts at time of mAb prescription (baseline) and up to four visits ~ 3, 6, 9, and 12 months post-baseline were reviewed for safety, tolerability, and outcome measures (monthly headache days [MHDs], headache intensity, and migraine-related disability [MIDAS]).

Safety and efficacy of ubrogepant in participants with major cardiovascular risk factors in two single-attack phase 3 randomized trials: ACHIEVE I and II.

Objective: To examine the safety and efficacy of ubrogepant for acute treatment of migraine across cardiovascular (CV) disease risk categories.

Methods: ACHIEVE I and II were multicenter, double-blind, single-attack, phase 3 trials in adults with migraine, with or without aura. Participants were randomized 1:1:1 to placebo or ubrogepant (50 or 100 mg in ACHIEVE I; 25 or 50 mg in ACHIEVE II), to treat one migraine attack of moderate or severe headache pain intensity.

Real-World Treatment Profiles, Clinical Outcomes, and Healthcare Resource Utilization of Patients with Migraine Prescribed Erenumab: A Multicenter Chart-Review Study of US Headache Centers.

Introduction: Erenumab, a first-in-class monoclonal antibody targeting the calcitonin gene-related peptide pathway, was approved by the US Food and Drug Administration in 2018 for the prevention of migraine in adults. There is limited data available on its impact in real-world settings. The study aim was to characterize the real-world treatment profiles, clinical outcomes, and healthcare resource utilization of patients prescribed erenumab from select major US headache centers.

Pharmacokinetics and safety of ubrogepant when coadministered with calcitonin gene-related peptide-targeted monoclonal antibody migraine preventives in participants with migraine: A randomized phase 1b drug-drug interaction study.

Objective: To evaluate the impact of two calcitonin gene-related peptide (CGRP)-targeted monoclonal antibodies (mAbs), erenumab and galcanezumab, on the pharmacokinetic (PK) profile, safety, and tolerability of ubrogepant.

Background: People taking CGRP-targeted mAbs for migraine prevention sometimes take ubrogepant, an oral small-molecule CGRP receptor antagonist, for acute treatment of breakthrough migraine attacks.

Design: In this two-arm, multicenter, open-label, phase 1b trial, adults with migraine were randomized to arm 1 (ubrogepant ± erenumab) or arm 2 (ubrogepant ± galcanezumab).

Efficacy of ubrogepant based on prior exposure and response to triptans: A post hoc analysis.

Objective: To determine the potential efficacy of ubrogepant for acute treatment of migraine based on historical experience with triptans.

Background: Although triptans have improved migraine treatment, their efficacy and tolerability may limit their utility in some individuals. Ubrogepant is a small-molecule, oral calcitonin gene-related peptide receptor antagonist approved by the Food and Drug Administration for acute treatment of migraine in adults.

Time course of efficacy of ubrogepant for the acute treatment of migraine: Clinical implications.

Background: The full utility of an acute treatment requires examination of the entire time course of effect during a migraine attack. Here the time course of effect of ubrogepant is evaluated.

Methods: ACHIEVE-I and -II were double-blind, single-attack, Phase 3 trials.

No "Wearing-Off Effect" Seen in Quarterly or Monthly Dosing of Fremanezumab: Subanalysis of a Randomized Long-Term Study.

Objective: To evaluate whether quarterly or monthly administration of fremanezumab for migraine prevention exhibits a pattern of decreased efficacy toward the end of the dosing interval (wearing-off effect).

Background: The main goals of migraine preventive treatment are to reduce the frequency, severity, and duration of migraine attacks, and migraine-associated disability. Wearing-off refers to the phenomenon whereby clinical symptoms return or worsen before the next dose of a drug is due and has been reported previously with migraine preventive medications.

Clinician-Patient Dialogue About Preventive Chronic Migraine Treatment.

Many new medications for the treatment of migraine are now available on the market. In the current evolving migraine treatment landscape, an individualized treatment approach is needed. This review provides practical recommendations on how to obtain a correct diagnosis and then engage in a long-term partnership with patients with the most severe form of migraine: chronic migraine (CM).

Patient-Reported Outcomes from a 1-Year, Real-World, Head-to-Head Comparison of OnabotulinumtoxinA and Topiramate for Headache Prevention in Adults With Chronic Migraine.

Introduction/objective: Chronic migraine (CM) is associated with impaired health-related quality of life and substantial socioeconomic burden, but many people with CM are underdiagnosed and do not receive appropriate preventive treatment. OnabotulinumtoxinA and topiramate have demonstrated (treatment benefit under ideal conditions) for the prevention of headaches in people with CM in clinical trials, but real-world studies suggest markedly different clinical (treatment benefit based on a blend of efficacy and tolerability). This study sought to evaluate patient-reported outcomes (PROs) of onabotulinumtoxinA versus topiramate immediate release for people with CM.

Mechanism of Action of OnabotulinumtoxinA in Chronic Migraine: A Narrative Review.

Objective: To review the literature on the mechanism of action of onabotulinumtoxinA in chronic migraine.

Background: OnabotulinumtoxinA is a chronic migraine preventive treatment that significantly reduces headache frequency. The traditional mechanism described for onabotulinumtoxinA - reducing muscle contractions - is insufficient to explain its efficacy in migraine, which is primarily a sensory neurological disease.

Lasmiditan mechanism of action - review of a selective 5-HT agonist.

Migraine is a leading cause of disability worldwide, but it is still underdiagnosed and undertreated. Research on the pathophysiology of this neurological disease led to the discovery that calcitonin gene-related peptide (CGRP) is a key neuropeptide involved in pain signaling during a migraine attack. CGRP-mediated neuronal sensitization and glutamate-based second- and third-order neuronal signaling may be an important component involved in migraine pain.