Sandhya Sapra

A Controlled Trial of Erenumab for Episodic Migraine

BACKGROUND We tested erenumab, a fully human monoclonal antibody that inhibits the calcitonin gene–related peptide receptor, for the prevention of episodic migraine. METHODS We randomly assigned patients to receive a subcutaneous injection of either erenumab, at a dose of 70 mg or 140 mg, or placebo monthly for 6 months. The primary end point was the change from baseline to months 4 through 6 in the mean number of migraine days per month. Secondary end points were a 50% or greater reduction in mean migraine days per month, change in the number of days of use of acute migraine–specific medication, and change in scores on the physical‐impairment and everyday‐activities domains of the Migraine Physical Function Impact Diary (scale transformed to 0 to 100, with higher scores representing greater migraine burden on functioning). RESULTS A total of 955 patients underwent randomization: 317 were assigned to the 70‐mg erenumab group, 319 to the 140‐mg erenumab group, and 319 to the placebo group. The mean number of migraine days per month at baseline was 8.3 in the overall population; by months 4 through 6, the number of days was reduced by 3.2 in the 70‐mg erenumab group and by 3.7 in the 140‐mg erenumab group, as compared with 1.8 days in the placebo group (P<0.001 for each dose vs. placebo). A 50% or greater reduction in the mean number of migraine days per month was achieved for 43.3% of patients in the 70‐mg erenumab group and 50.0% of patients in the 140‐mg erenumab group, as compared with 26.6% in the placebo group (P<0.001 for each dose vs. placebo), and the number of days of use of acute migraine–specific medication was reduced by 1.1 days in the 70‐mg erenumab group and by 1.6 days in the 140‐mg erenumab group, as compared with 0.2 days in the placebo group (P<0.001 for each dose vs. placebo). Physical‐impairment scores improved by 4.2 and 4.8 points in the 70‐mg and 140‐mg erenumab groups, respectively, as compared with 2.4 points in the placebo group (P<0.001 for each dose vs. placebo), and everyday‐activities scores improved by 5.5 and 5.9 points in the 70‐mg and 140‐mg erenumab groups, respectively, as compared with 3.3 points in the placebo group (P<0.001 for each dose vs. placebo). The rates of adverse events were similar between erenumab and placebo. CONCLUSIONS Erenumab administered subcutaneously at a monthly dose of 70 mg or 140 mg significantly reduced migraine frequency, the effects of migraines on daily activities, and the use of acute migraine–specific medication over a period of 6 months. The long‐term safety and durability of the effect of erenumab require further study. (Funded by Amgen and Novartis; STRIVE ClinicalTrials.gov number, NCT02456740.)

Adherence and persistence with omalizumab and fluticasone/salmeterol within a managed care population.

Asthma control requires adherence with pharmacologic therapy. A medications mode of delivery may affect adherence. The purpose of this study was to compare medication persistence and adherence between patients newly treated with either an inhaled or injected asthma medication. Using a propensity-score-matched retrospective cohort study, we evaluated medication persistence and adherence over 1 year in adult asthma patients newly treated with omalizumab or fluticasone (500 microg)/salmeterol (50 microg) (FSC 500/50). Kaplan-Meier analysis was conducted to compare persistence between users of FSC 500/50 and omalizumab using the log-rank test. We conducted four sensitivity analyses. After propensity matching, the study sample included 213 omalizumab patients and 426 FSC 500/50 patients, with no statistically significant differences between groups on baseline measures. Mean adherence rates were 64.6% for omalizumab and 29.5% for FSC 500/50 (p < 0.0001). Fifty-four percent of omalizumab users were persistent at 1 year compared with 18.5% of FSC 500/50 users (p < 0.0001). In sensitivity analyses, we stratified patients by evidence of allergy and the results did not change. Adherence was more than twice as high and persistence was almost twice as high among omalizumab compared with FSC 500/50 users. The direction of our findings was consistent across all sensitivity analyses. In both omalizumab and FSC 500/50 cohorts, persistence decreased substantially over 1 year. Our study suggests that injected medications may have advantages in asthma treatment. A comprehensive program to improve adherence should address not just administration route but also patient factors that prevent proper medication use.

Poor disease control among insured users of high-dose combination therapy for asthma

Adherence to asthma treatment may not completely prevent exacerbations. Clinical trial results indicate that many highly adherent asthma patients still have symptoms. Little is known about the level of control achieved by adherent patients outside clinical trials. This study was designed to evaluate the extent of asthma control among insured patients who were highly adherent to combination controller therapy. We used an administrative claims database for this cohort study of patients aged 12-64 years. Patients were newly treated with fluticasone, 500 micrograms/salmeterol, 50 micrograms, between January 1, 2003 and June 30, 2004. Patients were stratified according to adherence levels: low (<50%), moderate (50-74%), and high (> or =75%). We compared rates of poor control. A logistic regression model was used to control for baseline differences. Among 3357 patients, the mean age was 40.5 +/- 13.6 years, and 64.1% were women. Sixty-one percent had low adherence, 20% had moderate adherence, and 19% had high adherence. Highly adherent patients were older, and more used fluticasone, 250 micrograms/salmeterol, 50 micrograms, during the preindex period than the other groups. Even after starting high-dose fluticasone/salmeterol, many patients with low, moderate, and high adherence had indicators of poor symptom control (28.9% [587/2030], 30.6% [209/682], and 30.7% [198/645], respectively). Patients who were highly adherent and used additional controller medications had rates of poor control that ranged from 23.1 to 31.2%. After adjusting for age, gender, and baseline characteristics, results were similar. Many patients continue to have poor asthma control despite being adherent to high-dose combination therapy or using additional controller medications.

Measuring the impact of migraine for evaluating outcomes of preventive treatments for migraine headaches

BackgroundMigraine is characterized by headache with symptoms such as intense pain, nausea, vomiting, photophobia, and phonophobia that significantly impact individuals’ lives. The objective of this study was to develop a strategy to measure outcomes from the patients’ perspectives for use in evaluating preventive treatments for migraine.MethodsThis study used a multi-stage process. The first stage included concept identification research through literature review, patient-reported outcome (PRO) instrument content review, and clinician interviews, and resulted in a list of concepts relevant to understand the migraine experience. These results informed the design of the subsequent concept elicitation stage that involved qualitative interviews of adults with migraine to understand their experiences. Information from these two stages was used to develop a conceptual disease model (CDM) of the migraine experience. This CDM was used to identify concepts of interest (COI) to evaluate patient-relevant outcomes for assessing treatment benefit of migraine prophylactics. In the final stage, existing PRO instruments were reviewed to assess coverage of concepts related to the selected COI.ResultsNine articles from 563 screened abstracts underwent full review to identify migraine-relevant concepts. This concept identification and subsequent concept elicitation interviews (N = 32; 21 episodic migraine; 11 chronic migraine) indicated that people with migraine experience difficulties during and between migraine attacks with considerable day-to-day variability in the impact on movement, ability to perform every day and social activities, and emotion. The CDM organized concepts as proximal to and more distal from disease-defining migraine symptoms, and was used to identify impact on physical function as the key COI. The item level review of PRO instruments revealed that none of the existing PRO instruments were suitable to collect data on impact of migraine on physical functioning, to evaluate treatment benefit.ConclusionsThe impact of migraine includes impairments in functioning during and between migraine attacks that vary considerably on a daily basis. There is a need for novel PRO instruments that reflect patients’ migraine experience to assess treatment benefit of migraine prophylactics. These instruments must evaluate the concepts identified and be able to capture the variability of patients’ experience.

Care of asthma patients in relation to guidelines.

Clinical asthma care may have to change to be brought in line with Expert Panel Report 3 (EPR3) guidelines, which recommend increased intensity of therapy (steps) to treat uncontrolled asthma. This study determined if asthma therapy steps can be identified using claims data and if patients have appropriate step-up in therapy if their disease is not controlled. A cohort study was performed using an administrative claims database and involving patients 12-64 years old with uncontrolled asthma events (either impairment or risk). Patients were assigned to a preindex step (6 months before the index date) and postindex steps (1 year after the index date). The primary study outcome was a change in therapy steps. We used logistic regression to identify variables predictive of an increase in step. Our algorithm for assigning steps appeared internally valid; patients identified as being at higher steps saw more specialists and had higher levels of asthma risk. Among 14,781 patients for which a step-up option existed, 12.4-41.3% had a step-up in therapy after an uncontrolled asthma event. For all steps, high-risk patients had higher odds of having a step-up in therapy than low-risk patients. The odds ratio for appropriate therapy increased with increasing baseline step: from 1.50 for step 2 versus step 1, to 11.41 for step 5 versus step 1. Steps can be assigned using claims data. Bringing care in line with EPR3 guidelines will require significant changes from current practice but will improve quality by reducing use of oral corticosteroids and increasing use of inhaled steroids.

Psychometric Evaluation of a Novel Instrument Assessing the Impact of Migraine on Physical Functioning: The Migraine Physical Function Impact Diary

The objective of this study was to evaluate the measurement properties of the Migraine Physical Function Impact Diary (MPFID), a novel patient‐reported outcome (PRO) measure for assessing the impact of migraine on physical functioning.

Estimating the clinical effectiveness and value-based price range of erenumab for the prevention of migraine in patients with prior treatment failures: a US societal perspective

Abstract Background: Frequent migraine with four or more headache days per month is a common, disabling neurovascular disease. From a US societal perspective, this analysis models the clinical efficacy and estimates the value-based price (VBP) for erenumab, a fully human monoclonal antibody that inhibits the calcitonin gene-related peptide receptor. Methods: A Markov health state transition model was developed to estimate the incremental costs, quality-adjusted life-years (QALYs), and value-based price range for erenumab in migraine prevention. The model comprises “on preventive treatment”, “off preventive treatment”, and “death” health states across a 10-year time horizon. The evaluation compared erenumab to no preventive treatment in episodic and chronic migraine patients that have failed at least one preventive therapy. Therapeutic benefits are based on estimated changes in monthly migraine days (MMD) from erenumab pivotal clinical trials and a network meta-analysis of migraine studies. Utilities were estimated using previously published mapping algorithms. A VBP analysis was performed to identify maximum erenumab annual prices at willingness-to-pay (WTP) thresholds of

Phase 3, randomised, double-blind, placebo-controlled study to evaluate the efficacy and safety of erenumab (amg 334) in migraine prevention: primary results of the strive trial

100,000–

Factors Associated with Direct Health Care Costs Among Patients with Migraine

200,000 per QALY. Estimates of VBP under different scenarios such as choice of different comparators, assumptions around inclusion of placebo effect, and exclusion of work productivity losses were also generated. Results: Erenumab resulted in incremental QALYs of 0.185 vs supportive care (SC) and estimated cost offsets due to reduced MMD of

Direct and Indirect Healthcare Resource Utilization and Costs Among Migraine Patients in the United States

8,482 over 10 years, with an average duration of treatment of 2.01 years. The estimated VBP at WTP thresholds of