https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1524-4733.2008.00404.x

The Burden of Migraine in the United States: Current and Emerging Perspectives on Disease Management and Economic Analysis

Background:This study is meant to compare the direct and indirect cost of migraine headache care before and after migraine surgery and to evaluate any postoperative changes in patient participation in daily activities.Methods:Eighty-nine patients enrolled in a migraine surgery clinical trial complet

A socioeconomic analysis of surgical treatment of migraine headaches.

The use of botulinum toxin type A (BoNT-A) as a preventive headache treatment is increasing but remains controversial and the subject of much discussion. Several factors contribute to this discussion, the most important of which is the question of the evidence of its efficacy in headache prevention. The limited number of conclusive placebo-controlled trials has led to the challenge that the data do not differentiate a genuine treatment effect from a placebo response. Without doubt, an intensive neurologic consultation involving muscle palpation and injection of a highprofile treatment inevitably will create some element of placebo response. Questions also arise as to how the muscle-relaxing effects of BoNT-A could be relevant to the pathophysiology of migraine. To confound matters further, the cost of BoNT-A therapy is relatively high. Should these issues rule out a role for BoNT-A in the long-term treatment of headache? Unfortunately, the current arsenal of preventive headache treatments is not replete with effective, proven, welltolerated, low-cost pharmacotherapeutic agents. Patients are frequently dissatisfied with their treatment, and physicians need to explore new approaches if

Botulinum Toxin Type A for the Treatment of Headache: Pro

Objective.—To examine the characteristics of chronic daily headache sufferers who use emergency departments (EDs) and identify factors predictive of ED visits.



Background.—Several large clinical trials have found that a sizable subset of headache patients uses EDs frequently, although such visits should be preventable.



Methods.—Participants in two large clinical trials provided baseline data on ED use, hospitalizations, disability, daily activities, and quality of life.



Results.—Of the 785 patients included, 182 (23.2%) reported at least 1 ED visit over the past year. Most of these patients (82.9%) reported one to six visits; however, 4.4% reported ≥21 visits (mean 5.0; SD 8.5). The percentage of patients with overnight hospitalizations during the previous year was significantly greater in the ED user group than non-ED user group (17.6% vs 1.7%; P < .001), as was the number of visits to healthcare practitioners (median 24.3 vs 11.8; P < .001). Compared with non-ED users, a higher percentage of ED users reported severe disability on the Migraine Disability Assessment Scale (MIDAS) (85.7% vs 69.3%, P < .001) and indicated that their headache more negatively impacted mood and daily activities (all P < .05). ED users also had significantly higher depression scores and lower scores on all domains of the Short Form-36 (SF-36) (all P < .05). In a logistic regression model, patient age, neurologist visit, severe (vs not severe) rating on the MIDAS, Role Physical (SF-36), and prior overnight hospitalization were significant predictors of ED use (max-rescaled R2= 21.0%).



Conclusions.—Patients seeking ED treatment for chronic daily headache are more severely affected and have more unmet medical needs than those who do not use the ED. Management strategies that help prevent frequent ED use might be possible.

Characterization and Prediction of Emergency Department Use in Chronic Daily Headache Patients

Objective Investigate the safety and pharmacokinetics (PK) of INP104, intranasal dihydroergotamine mesylate (DHE) administered via a Precision Olfactory Delivery (POD® ) device, (Impel NeuroPharma, Seattle, WA) vs intravenous (IV) DHE and DHE nasal spray (Migranal® ) in healthy adult subjects. Methods This was a Phase 1, open-label, randomized, single-dose, 3-period, 3-way crossover study. Subjects received a single dose of A) INP104 1.45 mg (a drug-device combination product composed of DHE and the I123 POD device); B) DHE 45® Injection (IV) 1.0 mg; and C) DHE by Migranal® Nasal Spray 2.0 mg. Plasma levels of DHE and the major bioactive metabolite, 8'OH-DHE, were measured, and PK parameters were determined for both. Comparative bioavailability (BA) was assessed by calculating the ratio of the geometric means between treatments for Cmax and AUC0-inf on the ln-transformed data. Safety was assessed from adverse events, vital signs, electrocardiograms, and clinical laboratory values. Results Thirty-eight subjects were enrolled, 36 were dosed with at least 1 IP and 27 were included in the evaluation of PK and comparative BA. DHE plasma levels following INP104 1.45 mg administration reached 93% of Cmax by 20 minutes and were comparable to IV DHE 1.0 mg by 30 minutes (1219 ng/mL for INP104 vs 1224 ng/mL for IV DHE), which was the Tmax for INP104. From 30 minutes onward, DHE levels for INP104 closely matched those of IV DHE to 48 hours, the last time point measured. In comparison, the Cmax for Migranal was 299.6 pg/mL (approximately 4-fold less than INP104) and occurred at 47 minutes, 17 minutes later than INP104. Plasma DHE AUC0-inf were 6275, 7490, and 2199 h*pg/mL for INP104, IV DHE, and Migranal, respectively. Variability (coefficient of variation [CV%]) for Cmax and AUC0-inf for INP104 compared to Migranal indicated more consistent delivery with INP104. In the BA comparison using the PK population (subjects who had received all 3 treatments), the ratios of geometric means (percent) for Cmax and AUC0-inf were 7.9% and 74.2%, respectively, for INP104: IV DHE, and 445% and 308% for INP104: Migranal. Mean plasma concentration profiles for 8'-OH-DHE were proportionately lower and followed a similar profile to the parent compound, regardless of route of administration (IN vs IV) or delivery system (Migranal vs INP104). Treatment emergent AEs (TEAEs), of mostly mild intensity, were reported by 15/31 (48.4%), 21/32 (65.6%), and 14/34 (41.2%) subjects after INP104, IV DHE, and Migranal, respectively. Treatment-related TEAEs occurred in 6/31 (19.4%), 16/32 (50.0%), and 4/34 (11.8%) subjects after INP104, IV DHE, and Migranal, respectively. Conclusion INP104 met the predefined statistical criteria for comparative bioavailability with IV DHE and Migranal. The shorter time to reach Cmax and at 4 times the plasma concentration of DHE in comparison to Migranal combined with a favorable tolerability profile support further investigation of INP104 as an effective, well tolerated, and non-invasive treatment for acute episodic migraine.

https://headachejournal.onlinelibrary.wiley.com/doi/epdf/10.1111/head.13476

STOP 101: A Phase 1, Randomized, Open-Label, Comparative Bioavailability Study of INP104, Dihydroergotamine Mesylate (DHE) Administered Intranasally by a I123 Precision Olfactory Delivery (POD® ) Device, in Healthy Adult Subjects.

To provide a more comprehensive accounting of direct cost of treating headaches, it is imperative to quantify the cost of emergency room (ER) services specific to treating headaches. Published cost...

John Carlsen

Papers

Estimating the cost of an emergency room visit for migraine headache