Effects of galcanezumab on acute medication use and health care resource utilization in treatment-resistant migraine: results from randomized, double blind, placebo-controlled clinical trial, conquer

IntroductionAcute headache medication use (AHM) and health care resource utilization (HCRU) in patients with protocol-defined treatment-resistant migraine treated with galcanezumab (GMB).Material and methodsIn the 3-month double-blind (DB) study phase, patients with episodic or chronic migraine and 2-4 migraine preventive category failures due to lack of effectiveness or safety/tolerability, received GMB 120 mg/month (following initial 240 mg loading dose) or placebo (PBO); an optional 3-month open-label (OL) GMB treatment followed. AHM was self-reported daily with eDiary and paper-forms. HCRU was reported at baseline (retrospectively for previous 6 months) and at monthly visits.ResultsOf the 462 patients (GMB n=232, PBO n=230), baseline mean (±SD) days/month of AHM was 12.3 (±6.0); 44.8% had AHM overuse. The percentage of patients reporting migraine-specific HCRU at baseline in the GMB and PBO groups were respectively: 40% and 50% healthcare-professional visits (HCP), 6% and 5% emergency-room (ER) visits, and in each, 2% hospitalizations. LS mean reductions from baseline in the mean number of days/month with AHM in the DB was greater for the GMB group (3.9 to 4.5 days) compared to PBO (0.4 to 1.0 days) in each of the first 3 months; change difference, -3.1 to -3.5, p<0.001 at each month during Months 1-3. During theOL, reductions from baseline ranged -4.7 to -5.3 days; prior PBO group reductions were comparable to that observed in GMB. During the DB, reductions from baseline of migraine-specific HCP (per 100 person- years) were numerically greater with GMB than PBO (-215.5 vs -155.3); during OL, the prior PBO group reductions (-212.9) were similar to GMB (-222.6). For both groups, migraine-specific ER visits were <13 and hospitalizations were <2 per 100 person-years during the DB and OL.ConclusionsGMB-treated patients with treatment-resistant migraine had clinically meaningful reductions in days with AHM and numerically greater reductions in migraine-specific HCP. The abstract was previously presented at EHF (2020)

Preventing episodic migraine with caloric vestibular stimulation: a randomized controlled trial

Objective: To evaluate the safety and efficacy of a novel solid-state, caloric vestibular stimulation (CVS) device to provide adjuvant therapy for the prevention of episodic migraine in adult migraineurs. Background: Migraine causes significant disability in ~12% of the world population. No current migraine preventive treatment provides full clinical relief, and many exhibit high rates of discontinuation due to adverse events. Thus, new therapeutic options are needed. CVS may be an effective and safe adjuvant-therapy for the prevention of episodic migraine. Methods: In a multicenter, parallel-arm, block-randomized, placebo-controlled clinical trial (clinicaltrials.gov: NCT01899040), subjects completed a 3-month treatment with the TNMTM device for CVS (refer to Figure 2 for patient enrollment and allocation). The primary endpoint was the change in monthly migraine days from baseline to the third treatment month. Secondary endpoints were 50% responder rates, change in prescription analgesic usage and difference in total subjective headache-related pain scores. Device safety assessments included evaluation of any impact on mood, cognition or balance. Results: Per-protocol, active-arm subjects showed immediate and steady declines in migraine frequency over the treatment period. After three months of treatment, active-arm subjects exhibited significantly fewer migraine days (-3.8 ± 0.5 from a baseline burden of 7.7 ± 0.5 migraine days). These improvements were significantly greater than those observed in control subjects (-1.1 ± 0.6 from a baseline burden = 6.9 ± 0.7 migraine days) and represented a therapeutic gain of -2.7 migraine days, CI = -0.9 to -4.7, p = 0.012. Active arm subjects also reported greater reductions in acute medication usage and monthly pain scores compared to controls. No adverse effects on mood, cognition or balance were reported. Subjects completed the trial with an average rate of 90% treatment adherence. No serious or unexpected adverse events were recorded. The rate of expected adverse events was similar across the active and the placebo groups, and evaluation confirmed that subject blinding remained intact. Conclusion: The TNM device for CVS appears to provide a clinically efficacious and highly tolerable adjuvant therapy for the prevention of episodic migraine

Migraine day frequency in migraine prevention: longitudinal modelling approaches

Background Health economic models are critical tools to inform reimbursement agencies on health care interventions. Many clinical trials report outcomes using the frequency of an event over a set period of time, for example, the primary efficacy outcome in most clinical trials of migraine prevention is mean change in the frequency of migraine days (MDs) per 28 days (monthly MDs [MMD]) relative to baseline for active treatment versus placebo. Using these cohort-level endpoints in economic models, accounting for variation among patients is challenging. In this analysis, parametric models of change in MMD for migraine preventives were assessed using data from erenumab clinical studies. Methods MMD observations from the double-blind phases of two studies of erenumab were used: one in episodic migraine (EM) (NCT02456740) and one in chronic migraine (CM) (NCT02066415). For each trial, two longitudinal regression models were fitted: negative binomial and beta binomial. For a thorough comparison we also present the fitting from the standard multilevel Poisson and the zero inflated negative binomial. Results Using the erenumab study data, both the negative binomial and beta-binomial models provided unbiased estimates relative to observed trial data with well-fitting distribution at various time points. Conclusions This proposed methodology, which has not been previously applied in migraine, has shown that these models may be suitable for estimating MMD frequency. Modelling MMD using negative binomial and beta-binomial distributions can be advantageous because these models can capture intra- and inter-patient variability so that trial observations can be modelled parametrically for the purposes of economic evaluation of migraine prevention. Such models have implications for use in a wide range of disease areas when assessing repeated measured utility values

Preventive treatment in migraine and the new US guidelines

E Estemalik, S TepperCleveland Clinic, Neurological Center for Pain, Cleveland, Ohio, USAAbstract: Migraine headaches are among the most common headache disorders seen in various practices. The prevalence of migraine headaches is 18% in women and 6% in men. While millions of Americans suffer from migraine headaches, roughly 3%&ndash;13% of identified migraine patients are on preventive therapy, while an estimated 38% actually need a preventive agent. The challenge among physicians is not only when to start a daily preventive agent but which preventive agent to choose. Circumstances warranting prevention have been described in the past, and in 2012, a new set of guidelines with an evidence review on preventive medications was published. A second set of guidelines provided evidence on nonsteroidal anti-inflammatory drugs, herbs, minerals, and vitamins for prevention of episodic migraine. This article describes the updated US guidelines for the prevention of migraines and also outlines the major studies from which these guidelines were derived.Keywords: US guidelines, Canadian guidelines, classification, preventive medicatio