Efficacy and Safety of Erenumab for Nonopioid Medication Overuse Headache in Chronic Migraine: A Phase 4, Randomized, Placebo-Controlled Trial.

Importance: Patients with chronic migraine and medication overuse headaches (CM-MOH) represent a particularly burdened subpopulation. This trial provides first, to our knowledge, American Academy of Neurology class I evidence for a preventive therapy in CM-MOH.

Objective: To assess erenumab efficacy and safety in patients with nonopioid CM-MOH.

Treatment patterns of patients with migraine eligible for anti-CGRP pathway monoclonal antibodies.

Introduction: Migraine is a debilitating neurological disorder, with a wide range of symptoms and disease burden, underscoring the heterogeneity of patients' disease characteristics and treatment needs. To characterize the profile of migraine patients in the US who may be eligible for preventive treatment with an anti-CGRP pathway mAb and to better understand treatment patterns and real-world use of acute and preventive medications for migraine, we conducted a retrospective cohort study of adult patients.

Methods: These patients were identified as having migraine using diagnosis codes or migraine-specific medication use (first = index) in the IQVIA PharMetrics® Plus database.

Situational prevention: Pharmacotherapy during periods of increased risk for migraine attacks.

The small molecule calcitonin gene-related peptide receptor antagonists (gepants) are the only drug class with medicines indicated for both the acute and preventive treatment of migraine. Given this dual capacity to both treat and prevent, along with their favorable tolerability profiles and lack of an association with medication-overuse headache, headache specialists have begun to use gepants in ways that transcend the traditional categories of acute and preventive treatment. One approach, called situational prevention, directs patients to treat during the interictal phase, before symptoms develop, in situations of increased risk for migraine attacks.

Commentary on 2022 guidelines on clinical trial design in cluster headache and further suggestions.

Background: New guidelines for cluster headache clinical trials were recently published. We welcome these new guidelines and raise additional considerations in trial methodologies.

Main Body: We present non-inferiority trials to overcome ethical issues with placebo use, and additionally discuss issues with trial recruitment.

Management of medication overuse headache.

Medication overuse headache (MOH) is a secondary headache characterized by frequent use of acute or symptomatic migraine medications at a sufficient frequency to transform patients from episodic to chronic migraine. MOH represents a significant medical problem, with a serious burden on patients' lives and on society as a whole. MOH patients often have additional comorbidities, and the clinical challenge of helping patients reduce acute medication use and revert to episodic headache can be marked.

Eptinezumab Demonstrated Efficacy Regardless of Prior Preventive Migraine Treatment Failure Type: Post Hoc Analyses of the DELIVER Study.

Introduction: In the DELIVER study, eptinezumab reduced monthly migraine days (MMDs) more than placebo in patients with 2-4 prior preventive migraine treatment failures. This post hoc analysis evaluated the efficacy of eptinezumab across the 24-week placebo-controlled period of the DELIVER study in subgroups defined by prior treatment failure type.

Methods: DELIVER (NCT04418765) randomized adults with migraine to eptinezumab 100 mg, 300 mg, or placebo, administered intravenously every 12 weeks.

Long-term effectiveness of eptinezumab in patients with migraine and prior preventive treatment failures: extension of a randomized controlled trial.

Background: Eptinezumab demonstrated efficacy in adults with migraine and prior preventive treatment failures in the placebo-controlled phase of the DELIVER clinical trial; its long-term effectiveness in this population has not yet been reported. The objective of this study was to evaluate the long-term effectiveness of eptinezumab in a migraine patient population during the 48-week extension phase of DELIVER.

Methods: DELIVER was conducted June 1, 2020 to September 15, 2022.

Healthcare costs and resource utilization in patients with migraine treated with erenumab: A retrospective, non-interventional study using claims data from the United States.

Objective: To assess healthcare costs and healthcare resource utilization (HCRU) among adult patients who newly initiated erenumab in the United States.

Methods: This retrospective, non-interventional analysis included adult patients (aged ≥18 years) newly initiating erenumab and who had three consecutive monthly claims for erenumab (11/1/2017-9/1/2019) from the Komodo Health database. Outcomes included migraine-related and all-cause costs, use of other preventive/acute migraine medications, and HCRU.

Multimodal Migraine Management and the Pursuit of Migraine Freedom: A Narrative Review.

Migraine is a neurologic disease with a complex pathophysiology that can be controlled with current treatment options but not cured. Therefore, treatment expectations are highly variable. The concept of migraine freedom was recently introduced and can mean different things, with some, for example, expecting complete freedom from headache and associated symptoms and others accepting the occasional migraine attack if it does not impact functioning.

Long-term efficacy and safety of erenumab in patients with chronic migraine and acute medication overuse: A subgroup analysis.

Objective: Assess the long-term efficacy and safety of erenumab in patients with chronic migraine with acute medication overuse.

Background: Overuse of acute medication in patients with chronic migraine has been linked to greater pain intensity and disability and may diminish the effectiveness of preventive therapies.

Methods: This 52-week open-label extension study followed a 12-week double-blind placebo-controlled study in which patients with chronic migraine were randomized 3:2:2 to placebo or once-monthly erenumab 70 mg or 140 mg.

The temporal trend of placebo response in migraine prevention from 1990 to 2021: a systematic literature review and meta-analysis with regression.

Background: Migraine affects 1.1 billion people globally and is the second leading cause of disability worldwide. In clinical trials, treatment efficacy is evaluated by comparing the differential responses in the treatment and placebo arms.

Sustained response of galcanezumab in migraine prevention: Patient-level data from a post hoc analysis in patients with episodic or chronic migraine.

Objective: To evaluate, at population and individual patient levels, the sustained response of reduction in migraine headache days in patients with migraine treated with galcanezumab.

Methods: This was a post hoc analysis of double-blind galcanezumab studies in patients with migraine: two 6-month episodic migraine (EM; EVOLVE-1/EVOLVE-2), one 3-month chronic migraine (CM; REGAIN), and one 3-month treatment-resistant migraine (CONQUER). Patients received monthly subcutaneous galcanezumab 120 mg (after 240 mg initial loading dose), galcanezumab 240 mg, or placebo.

Novel Migraine Treatments: A Review.

To present a review of the mechanisms of action, available clinical data, and safety profiles of novel migraine therapeutics to inform practice. PubMed, Medline, and Google Scholar were searched for randomized controlled trials (24 publications), review articles (15 publications), and other pertinent literature (16 publications) discussing the novel migraine therapeutics available between the years 2010 and 2021. All publications were reviewed to assess the mechanism of action, relevant clinical data, and side effect profile for each novel treatment.

Adding eptinezumab to brief patient education to treat chronic migraine and medication-overuse headache: Protocol for RESOLUTION-A phase 4, multinational, randomized, double-blind, placebo-controlled study.

Introduction: Migraine is a highly prevalent and disabling neurological disease. Excessive use of acute medications can lead to medication-overuse headache (MOH), occurring when a patient experiences an increasing number of headache and migraine days, despite taking greater amounts of acute medication. To treat MOH, a preventive migraine treatment and/or withdrawal of the overused medication(s) are advised.

Remote electrical neuromodulation for migraine prevention: A double-blind, randomized, placebo-controlled clinical trial.

Objective: To assess the clinical efficacy of remote electrical neuromodulation (REN), used every other day, for the prevention of migraine.

Background: Preventive treatment is key to managing migraine, but it is often underutilized. REN, a non-pharmacological acute treatment for migraine, was evaluated as a method of migraine prevention in patients with episodic and chronic migraine.

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.

Variability in recurrence rates with acute treatments for migraine: why recurrence is not an appropriate outcome measure.

Background: Headache recurrence is a common feature of acute therapies, whether approved or still in development, and continues to be a significant problem for both the patient and the clinician. Further complicating this issue is lack of standardization in definitions of recurrence used in clinical trials, as well as disparity in patient characteristics, rendering a comparison of different acute medications challenging. Recurrence has serious clinical implications, which can include an increased risk for new-onset chronic migraine and/or development of medication overuse headache.

Guidelines of the International Headache Society for Controlled Clinical Trials in Cluster Headache.

In 1995, a committee of the International Headache Society developed and published the first edition of the These have not been revised. With the emergence of new medications, neuromodulation devices and trial designs, an updated version of the International Headache Society is warranted. Given the scarcity of evidence-based data for cluster headache therapies, the update is largely consensus-based, but takes into account lessons learned from recent trials and demands by patients.

Role of Calcitonin Gene-Related Peptide on the Gastrointestinal Symptoms of Migraine-Clinical Considerations: A Narrative Review.

Calcitonin gene-related peptide (CGRP) is involved in several of the pathophysiologic processes underpinning migraine attacks. Therapies that target CGRP or its receptor have shown efficacy as preventive or acute treatments for migraine. Two small-molecule CGRP receptor antagonists (rimegepant and ubrogepant) are approved for the acute treatment of migraine, and 4 monoclonal antibodies (eptinezumab, erenumab, fremanezumab, and galcanezumab) are approved for migraine prevention; erenumab targets the canonical CGRP receptor, the others CGRP ligand.

Migraine treatment with external concurrent occipital and trigeminal neurostimulation-A randomized controlled trial.

Objective: To evaluate the efficacy and safety of concurrent non-invasive stimulation of occipital and trigeminal nerves in acute treatment of migraine with or without aura.

Background: Non-invasive neuromodulation devices stimulating a single peripheral nerve or anatomic distribution are routinely used by patients with migraine refractory to the first-line drugs or those who opt out of pharmaceutical treatment. Concurrent occipital and trigeminal stimulation was described in an invasive setting, and its safety cost outweighed its efficacy gain.

External Concurrent Occipital and Trigeminal Neurostimulation Relieves Migraine Headache: A Prospective, Randomized, Double-Blind, Sham-Controlled Trial.

Introduction: Current external peripheral nerve stimulation devices stimulate only one nerve. This prospective, randomized, double-blind, sham-controlled trial assessed efficacy, safety, and tolerability of a novel external combined occipital and trigeminal neurostimulation (eCOT-NS) device as a self-administered home treatment for migraine (RelivionMG, Neurolief Ltd; Netanya, Israel).

Methods: Episodic and chronic migraine subjects (N = 55) were randomized to receive active (n = 27) or sham (n = 28) treatment.