Benefit-Risk Assessment of Galcanezumab Versus Placebo for the Treatment of Episodic and Chronic Migraine Using the Metrics of Number Needed to Treat and Number Needed to Harm.

Introduction: Subcutaneous galcanezumab was an effective, well-tolerated preventive treatment for adults with episodic (EM) or chronic migraine (CM) in 4 phase 3 randomized controlled trials: EVOLVE-1, EVOLVE-2, REGAIN, and CONQUER. Number needed to treat (NNT) and to harm (NNH) are metrics of effect size used to evaluate benefit-risk profiles. This study evaluated NNT, NNH, and benefit-risk profiles (measured as likelihood to be helped or harmed, LHH) of galcanezumab 120 mg versus placebo in patients with EM or CM.

Patient Perspectives and Experiences of Preventive Treatments and Self-Injectable Devices for Migraine: A Focus Group Study.

Background: Although several self-injectable preventive treatments for migraine have become available, they are not yet widely used. Thus, understanding patients' perceptions towards them is limited.

Objective: This study aimed to inform the design of a preference-elicitation instrument, which is being developed to quantify preventive treatment preferences of people with migraine.

Shift from high-frequency to low-frequency episodic migraine in patients treated with Galcanezumab: results from two global randomized clinical trials.

Background: Patients with episodic migraine (EM) with a higher-frequency of migraine headache days (HFEM: 8-14 migraine headache days/month) have a greater disease burden and a higher risk of progressing to chronic migraine (CM) with associated acute treatment overuse versus those with low-frequency EM (LFEM: 4-7 migraine headache days/month). In this post hoc analysis, we assessed the proportions of patients who shifted from HFEM to LFEM and to very low-frequency EM (VLFEM: 0-3 migraine headache days/month) status following treatment with galcanezumab versus placebo.

Methods: EVOLVE-1 and EVOLVE-2 were double-blind, Phase 3 studies in patients with EM.

Effect of galcanezumab on severity and symptoms of migraine in phase 3 trials in patients with episodic or chronic migraine.

Background: Galcanezumab, a humanized monoclonal antibody that binds calcitonin gene-related peptide, has demonstrated a significant reduction in monthly migraine headache days compared with placebo. Here, we analyze data from 3 randomized clinical trials (2 episodic trials [EVOLVE-1, EVOLVE-2] and 1 chronic trial [REGAIN]), to examine if galcanezumab also alleviates the severity and symptoms of migraine.

Methods: The episodic migraine trials were 6-month, double-blind studies in patients with episodic migraine (4-14 monthly migraine headache days).

Medication overuse in a subgroup analysis of phase 3 placebo-controlled studies of galcanezumab in the prevention of episodic and chronic migraine.

Introduction: Acute medication overuse is prevalent in patients with migraine.

Methods: In three phase 3, double-blind, randomized, placebo-controlled studies, patients with episodic migraine (EVOLVE-1 and EVOLVE-2) or chronic migraine (REGAIN) were randomized 2:1:1 to monthly subcutaneous injections of placebo or galcanezumab 120 or 240 mg for 3 or 6 months. This subgroup analysis evaluated mean changes in the number of monthly migraine headache days in each treatment among patients with versus without baseline acute medication overuse via mixing modelling with repeated measures.

Functional impairment and disability among patients with migraine: evaluation of galcanezumab in a long-term, open-label study.

Purpose: Migraine can negatively impact patient functioning and quality of life. Here, we report the effects of galcanezumab (GMB), a humanized monoclonal antibody that binds to calcitonin gene-related peptide, on patient-reported outcome (PRO) measures in migraine.

Methods: CGAJ was a Phase III, randomized, open-label study (12-month open-label and 4-month post-treatment follow-up) in patients with episodic or chronic migraine.

Effect of age on pharmacokinetics, efficacy, and safety of galcanezumab treatment in adult patients with migraine: results from six phase 2 and phase 3 randomized clinical trials.

Background: Migraine clinical profile may change with age, making it necessary to verify that migraine treatments are equally safe and effective in older patients. These analyses evaluated the effects of patient age on the pharmacokinetics (PK), efficacy, and safety of galcanezumab for prevention of migraine.

Methods: Analyses included efficacy data from three double-blind phase 3 clinical trials: two 6-month studies in episodic migraine (EVOLVE-1, EVOLVE-2: N = 1773) and one 3-month study in chronic migraine (REGAIN:N = 1113).

Evaluation of injection-site-related adverse events with galcanezumab: a post hoc analysis of phase 3 studies in participants with migraine.

Background: Injection-site reactions have been reported with biologicals. In this post hoc analysis of Phase 3 studies in participants with migraine, we provide a comprehensive overview and detailed summary of injection-site reaction with galcanezumab.

Methods: Data were obtained from two randomised clinical studies in participants with episodic migraine (EVOLVE-1 and EVOLVE-2), one randomised study in participants with chronic migraine (REGAIN) and one open-label study (Study CGAJ) in participants with episodic or chronic migraine.

Correction to: Safety and tolerability of monthly galcanezumab injections in patients with migraine: integrated results from migraine clinical studies.

Following publication of the original article [1], the authors noticed an error in the values for 'Hypersensitivity SMQ' and 'Rash' in Table 7.

Safety and tolerability of monthly galcanezumab injections in patients with migraine: integrated results from migraine clinical studies.

Background: Galcanezumab, a humanized monoclonal antibody that selectively binds to calcitonin gene-related peptide, has demonstrated a significant reduction in monthly migraine headache days in phase 2 and 3 trials. In these analyses, we aimed to evaluate the safety and tolerability of galcanezumab compared with placebo for prevention of episodic or chronic migraine.

Methods: Data were integrated from three double-blind clinical studies for the up to 6-month galcanezumab exposure group (N = 1435), and from five clinical studies for the up to 1-year all-galcanezumab exposure group (N = 2276).

Correction to: Galcanezumab in episodic migraine: subgroup analyses of efficacy by high versus low frequency of migraine headaches in phase 3 studies (EVOLVE-1 & EVOLVE-2).

After publication of our article [1] we were notified that the data presented in the upper row of Fig. 7 was inadvertently the least square mean change from baseline (standard error) at Month 6 rather than the overall average of Month 3 and Month 6. The figure legend and discussion of the data in the text were and are correct.

Galcanezumab in episodic migraine: subgroup analyses of efficacy by high versus low frequency of migraine headaches in phase 3 studies (EVOLVE-1 & EVOLVE-2).

Background: Patients with high-frequency episodic migraine (HFEM) have a greater disease burden than those with low-frequency episodic migraine (LFEM). Acute treatment overuse increases the risk of migraine chronification in patients with HFEM. Galcanezumab, a humanized monoclonal antibody binding calcitonin gene-related peptide (CGRP), is effective for migraine prevention with a favorable safety profile.

Effect of Galcanezumab Following Treatment Cessation in Patients With Migraine: Results From 2 Randomized Phase 3 Trials.

Objective: We examined the efficacy and safety of galcanezumab after treatment cessation in randomized double-blind, placebo-controlled, migraine prevention studies (EVOLVE-1; EVOLVE-2).

Background: Galcanezumab is indicated for migraine prevention in adults.

Methods: Adults with episodic migraine were enrolled into EVOLVE-1 and EVOLVE-2, which randomized 858 and 915 patients, respectively, to galcanezumab 120 mg (an initial 240-mg loading dose), galcanezumab 240 mg, or placebo, administered subcutaneously once monthly for 6 months.

Preventive effects of galcanezumab in adult patients with episodic or chronic migraine are persistent: data from the phase 3, randomized, double-blind, placebo-controlled EVOLVE-1, EVOLVE-2, and REGAIN studies.

Background: Maintenance of effect following treatment with galcanezumab compared to placebo in adult patients with episodic or chronic migraine was evaluated.

Methods: In 2 similarly designed studies of patients with episodic migraine (6 months) and 1 study of patients with chronic migraine (3 months), patients randomized in a 1:1:2 ratio received a subcutaneous injection of galcanezumab 120 mg/month (after an initial loading dose of 240 mg) or 240 mg/month or placebo. Maintenance of effect during the double-blind phase was evaluated based on a comparison of the percentages of galcanezumab- and placebo-treated patients with maintenance of 30, 50, 75, and 100% response (defined as ≥30, ≥50, ≥75, and 100% reduction from baseline in monthly migraine headache days [MHD]) at an individual patient level.

Patient satisfaction, health care resource utilization, and acute headache medication use with galcanezumab: results from a 12-month open-label study in patients with migraine.

Background: Effects of galcanezumab, a monoclonal antibody against calcitonin gene-related peptide, on patient satisfaction, health care resource utilization (HCRU), and acute medication use were evaluated in a long-term, open-label study in patients with migraine.

Methods: Patients with episodic (78.9%) or chronic migraine (21.

A phase 3, long-term, open-label safety study of Galcanezumab in patients with migraine.

Background: Galcanezumab, a humanized monoclonal antibody that selectively binds to the calcitonin gene-related peptide, has demonstrated in previous Phase 2 and Phase 3 clinical studies (≤6-month of treatment) a reduction in the number of migraine headache days and improved patients' functioning. This study evaluated the safety and tolerability, as well as the effectiveness of galcanezumab for up to 12 months of treatment in patients with migraine.

Methods: Patients diagnosed with episodic or chronic migraine, 18 to 65 years old, that were not exposed previously to galcanezumab, were randomized to receive galcanezumab 120 mg or 240 mg, administered subcutaneously once monthly for a year.

Comparison between prefilled syringe and autoinjector devices on patient-reported experiences and pharmacokinetics in galcanezumab studies.

Purpose: The aim of this study was to compare the usability and patient-rated experiences of an autoinjector with a prefilled syringe in patients with migraine, who self-administered galcanezumab, and to compare pharmacokinetic parameters between these devices.

Materials And Methods: Patient-rated experiences with an investigational autoinjector and a prefilled syringe were compared in an open-label, 12-month study of once-monthly injections of galcanezumab 120 or 240 mg (NCT02614287). Patient-rated ease of usability was assessed with the Subcutaneous Administration Assessment Questionnaire (SQAAQ) and compared between devices.

Evaluation of Galcanezumab for the Prevention of Episodic Migraine: The EVOLVE-1 Randomized Clinical Trial.

Importance: Migraine is a disabling neurological disease characterized by severe headache attacks. Treatment options reduce migraine frequency for many patients, but adverse effects lead to discontinuation in many patients.

Objective: To demonstrate that galcanezumab is superior to placebo in the prevention of episodic migraine with or without aura.

Is the Noradrenergic Symptom Cluster a Valid Construct in Adjunctive Treatment of Major Depressive Disorder?

Objective: To identify symptoms potentially representative of a noradrenergic symptom cluster as possible predictors of response to the selective norepinephrine reuptake inhibitor (NRI) edivoxetine when used as monotherapy or adjunctive treatment in patients with DSM-IV-TR major depressive disorder (MDD).

Methods: Pooled data from 4 adjunctive treatment trials (selective serotonin reuptake inhibitor [SSRI] + edivoxetine 6-18 mg/d vs SSRI + placebo; N = 2,066) and data from 1 monotherapy trial (edivoxetine 6-18 mg/d versus placebo; N = 495) were used to identify predictors of response related to noradrenergic symptoms using a resampling-based ensemble tree method. The trials were conducted from 2008 to 2013.

Impact of non-remission of depression on costs and resource utilization: from the COmorbidities and symptoms of DEpression (CODE) study.

Objective: To determine the economic impact of sustained non-remission of depression on the total annual all-cause healthcare costs of patients with a history of depression.

Methods: Adults with ≥2 claims with depression diagnosis codes from the HealthCore Integrated Research Database were invited to participate in this retrospective/prospective fixed-cohort repeated-measures study. Patients with scores >5 at initial survey and 6 month assessment on the Quick Inventory of Depressive Symptomatology (QIDS-SR) were considered to be in 'sustained non-remission', while those with scores ≤5 at both assessments were considered to be in 'sustained remission'.

Incidence of tardive dyskinesia in older adult patients treated with olanzapine or conventional antipsychotics.

Background: The risk of persistent tardive dyskinesia (TD) was compared in patients with acute psychosis or agitation aged 55 years or older who were treated with olanzapine (OLZ) or conventional antipsychotic (CNV) drug therapy.

Methods: Patients without TD were randomized to treatment with OLZ (2.5-20 mg/d; n = 150) or CNV (dosed per label; n = 143).

A short-term, multicenter, placebo-controlled, randomized withdrawal study of a metabotropic glutamate 2/3 receptor agonist using an electronic patient-reported outcome device in patients with schizophrenia.

This 6-week, multicenter, randomized withdrawal, placebo-controlled trial sought to determine whether symptoms of physical dependence occur after abrupt cessation of pomaglumetad methionil (LY2140023 monohydrate), a metabotropic glutamate 2/3 receptor agonist, in patients with schizophrenia. Eligible outpatients, 18 to 65 years old who required a modification or initiation of antipsychotic medication received 4 weeks of pomaglumetad methionil during open-label treatment and then were randomized, double-blind, to continue pomaglumetad methionil or receive placebo for 2 weeks. The primary outcome compared results of the 3-day moving mean of the total score on the Discontinuation Symptom Checklist-Modified Rickels for pomaglumetad methionil-treated patients with those on placebo during the randomized withdrawal phase.