Real-world effectiveness of dupilumab in patients with asthma: Findings from the US ADVANTAGE study.

BACKGROUND: Dupilumab is approved as an add-on maintenance therapy for patients (≥6 years) with moderate-to-severe asthma. Better understanding of real-world effectiveness is needed. OBJECTIVE: To characterize the real-world effectiveness of dupilumab in asthma management. METHODS: This retrospective study included patients (≥12 years of age) diagnosed with asthma, initiating dupilumab between November 2018 and September 2020. The study used a US electronic medical record database (TriNetX Dataworks, Cambridge, Massachusetts). Asthma exacerbation rates before and after the initiation of dupilumab were analyzed using generalized estimating equations models with Poisson probabilistic link to estimate incidence rate ratios (IRRs). Sensitivity analyses were conducted based on previous exacerbation data, eosinophil levels, history of atopic dermatitis or chronic rhinosinusitis with nasal polyps, previous use of biologics, and presence of SARS-CoV-2 (COVID-19). RESULTS: A total of 2400 patients initiating dupilumab met all study criteria. After initiation of dupilumab, risk of asthma exacerbation was reduced by 44% (IRR, 0.56; 95% CI, 0.47-0.57; P = <0.0001) and systemic corticosteroid prescriptions by 48% (IRR, 0.52; 95% CI, 0.48, 0.56; P = <0.0001) compared with those before initiation of dupilumab. Adjustment for COVID-19 showed a greater reduction in asthma exacerbations (IRR, 0.50; 95% CI, 0.45-0.55; P = <0.0001). CONCLUSION: Current real-world efficacy evidence indicates that dupilumab reduces asthma exacerbations and total systemic corticosteroid prescriptions in clinical practice. The effectiveness of dupilumab was observed independent of exacerbation history, eosinophil levels, or COVID-19 impact.

Effectiveness of Nirmatrelvir-Ritonavir for the Prevention of COVID-19-Related Hospitalization and Mortality: A Systematic Literature Review.

BACKGROUND: Nirmatrelvir/ritonavir (NMV/r) is an oral antiviral drug used to treat mild-to-moderate coronavirus disease 2019 (COVID-19) in patients aged 12 years or older at high risk of progression to severe disease (eg, hospitalization and death). Despite being the preferred option for outpatient treatment in the majority of countries worldwide, NMV/r is currently underutilized in real-world clinical practice. AREAS OF UNCERTAINTY: As numerous real-world studies have described patient outcomes following treatment with NMV/r, this systematic literature review provides a comprehensive summary of evidence on NMV/r effectiveness against hospitalization and mortality further organized by clinically meaningful categories, such as acute versus longer-term follow-up, age, underlying health conditions, and vaccination status, to help inform health care decision making. DATA SOURCES: We searched Embase and PubMed (December 22, 2021-March 31, 2023) and congress abstracts (December 1, 2021-December 31, 2022) for reports describing NMV/r effectiveness. THERAPEUTIC ADVANCES: In total, 18 real-world studies met final selection criteria. The evidence showed that NMV/r significantly reduced postinfection risk of all-cause and COVID-19-related hospitalization and mortality in both acute (≤30 days) (21%-92%) and longer-term (>30 days) (1%-61%) follow-up. The reduction in postinfection risk was higher when treatment was received within 5 days of symptom onset. Real-world effectiveness of NMV/r treatment was observed regardless of age, underlying high-risk conditions, and vaccination status. CONCLUSION: The systematic literature review findings demonstrated the effectiveness of NMV/r against hospitalization and mortality during the Omicron period among individuals at high risk of progression to severe COVID-19 disease.

Real-world effectiveness of dupilumab versus benralizumab and mepolizumab.

INTRODUCTION: In the United States, this real-world study compared the effectiveness of dupilumab, benralizumab, andmepolizumab in reducing exacerbations and systemic corticosteroid (SCS) prescriptions among patients with asthma. METHODS: Patients (12 years old) who initiated dupilumab, benralizumab, or mepolizumab (index) between November 2018 and September 2020 were identified by using electronic medical record data. Subjects were included if they had greater than or equal to 12 months of data before and after the index date and two or more severe asthma-related exacerbations before the index date. Differences in baseline characteristics were addressed by using inverse probability treatment weighting (IPTW). Pairwisecomparisons between dupilumab and benralizumab, or mepolizumab were conducted by using negative binomial regression, adjusting for baseline rates and unbalance characteristics (greater than or equal to 10% standardized differences) after IPTW. RESULTS: Overall, a total of 1737 subjects met all criteria: 825 dupilumab, 461 benralizumab, and 451 mepolizumab initiators.In the postindex period, dupilumab was associated with a 24% and 28% significant reduction in the risk of severe asthmaexacerbations versus benralizumab (incidence rate ratio [IRR] 0.76 [95% confidence interval {CI}, 0.67-0.86)] and mepolizumab(IRR 0.72 [95% CI, 0.63-0.82]), respectively. In addition, dupilumab treatment significantly reduced SCS prescriptionsby 16% and 25% versus benralizumab and mepolizumab, respectively (p < 0.05). CONCLUSION: This study represents one of the largest real-world comparisons of biologics (dupilumab, benralizumab, and mepolizumab) for asthma in the United States to date. This analysis shows that the use of dupilumab was associated with a significantly greater reduction in both severe asthma exacerbations and SCS prescriptions compared with benralizumab and mepolizumab.

A structured review evaluating content validity of the Asthma Control Test, and its consistency with U.S. guidelines and patient expectations for asthma control.

OBJECTIVE: To assess whether the content of the Asthma Control Test (ACT) served as a valid measure of asthma control (i.e., content validity) by mapping ACT items to the National Heart, Lung and Blood Institute (NHLBI) guideline asthma control definitions, and to language used by patients to describe their asthma. DATA SOURCES: PubMed and EMBASE databases were used for a structured literature analysis. STUDY SELECTIONS: Full-text, English-language articles that reported findings from qualitative studies conducted in adults, focusing on patient descriptors of asthma symptoms, impacts, or severity, were included. Pediatric studies, studies conducted in patients without asthma, and studies that did not contain qualitative data were excluded. RESULTS: ACT items reflected all domains of asthma impairment described in the NHLBI guidelines, except pulmonary function. Following the literature review, 28 full-text publications were identified that included patient descriptors that could be mapped to ACT items. For example, per ACT Item 1, patients described having trouble at work, school, and completing household chores; and, per ACT Item 2, patients used the phrase "short of breath" to describe asthma-associated symptoms. CONCLUSION: ACT item content corresponded well with the NHLBI guideline definitions of the impairment domain of asthma control (focused on asthma symptoms and impact), and we identified numerous examples in the literature indicating that ACT concepts and item content mirror the language patients use when discussing asthma symptoms and impact, and their degree of asthma control. This provides further evidence to support content validity of the ACT as a measure of asthma control.

Medication adherence in patients with asthma using once-daily versus twice-daily ICS/LABAs.

OBJECTIVE: This real-world observational study compared medication adherence and persistence among patients with asthma receiving the once-daily inhaled corticosteroid/long-acting ß2-agonist (ICS/LABA) fluticasone furoate/vilanterol (FF/VI) versus the twice-daily ICS/LABAs budesonide/formoterol (B/F) and fluticasone propionate/salmeterol (FP/SAL). METHODS: This retrospective cohort study conducted using IQVIATM Health Plan Claims Data included patients with asthma ≥18 years of age initiating ICS/LABA therapy with FF/VI, B/F, or FP/SAL between January 1, 2014 and June 30, 2016 (index date). Patients had ≥12 months and ≥3 months of continuous eligibility pre- and post-index date, respectively. Patients receiving FF/VI were separately matched 1:1 with patients receiving B/F or FP/SAL using propensity score matching (PSM) and multivariable regression to balance baseline covariates between cohorts. The primary endpoint was medication adherence, measured by proportion of days covered (PDC). Secondary endpoints included proportion of patients achieving PDC ≥ 0.5 and PDC ≥ 0.8 and persistence with index medication, measured by time to discontinuation (>45-day gap in therapy). RESULTS: After PSM, 3,764 and 3,339 patients receiving FF/VI were matched with patients receiving B/F or FP/SAL, respectively. Mean PDC was significantly higher for FF/VI versus B/F (0.453 vs 0.345; adjusted p < 0.001) and FP/SAL (0.446 vs 0.341; adjusted p < 0.001). The proportion of patients achieving PDC ≥ 0.5 or PDC ≥ 0.8, and treatment persistence were significantly higher for FF/VI versus B/F and FP/SAL (all p < 0.001). CONCLUSIONS: In this real-world study, patients initiating FF/VI had better adherence and lower risk of discontinuing treatment versus B/F or FP/SAL, suggesting that once-daily ICS/LABA treatment might improve adherence and persistence compared with twice-daily alternatives.

Adherence and usage patterns of inhaled corticosteroids-long-acting beta-agonists by using inhaler-monitoring technology.

Background: Results of previous research indicate that adherence to prescribed inhaled corticosteroid-long-acting beta2-agonist (ICS-LABA) asthma controller medications is suboptimal, yet actual daily-use patterns are unclear and may be influenced by regimen complexity or dosing frequency. Objective: To investigate real-world use of asthma medications by using inhaler sensors for the ICS-LABA controllers: twice-daily fluticasone propionate (FP) plus salmeterol (SAL) and once-daily fluticasone furoate (FF) plus vilanterol (VI); and albuterol rescue medication. Methods: This longitudinal, two-phase, observational study included adults with asthma-prescribed FP-SAL (phase I) or FF-VI (phase II), and albuterol metered-dose inhalers. The participants completed baseline and follow-up surveys, and used clip-on inhaler sensors to monitor real-time inhaler use over the 6-month study period. Pharmacy claims data for the 6-month follow-up period were used to assess refills of ICS-LABA and albuterol inhalers. Results: Patients who used twice-daily FP-SAL received a sufficient dose (≥2 actuations/day) approximately one third of the time, those on once-daily FF-VI received a sufficient dose (≥1 actuation/day) ∼60% of the time. Patients who used once-daily FF-VI were more likely to take their medication as prescribed versus those who used twice-daily FP-SAL. There were no significant differences in the percentage of albuterol-free days (FP-SAL, 68.06% [n = 241]; FF-VI, 72.67% [n = 127]; p = 0.230). Exploratory outcomes are reported in this article's Online Supplemental Material. Claims-based measures of adherence were higher than sensor-based measures, hence claims data may have overestimated adherence, whereas sensors may have more accurately measured patients' medication use. Conclusion: These data supported the use of inhaler sensors as tools to directly and accurately measure ICS-LABA adherence and rescue medication use, and the adherence benefits of once-daily versus twice-daily ICS-LABA regimens.

The Identification and Cost of Acute Chronic Obstructive Pulmonary Disease Exacerbations in a United States Population Healthcare Claims Database.

Almost half of chronic obstructive pulmonary disease (COPD) exacerbations are estimated to be inaccurately reported by patients, inconsistently recorded in medical records, or not measured due to coding errors inherent to administrative claims. This retrospective observational study aimed to develop an algorithm capable of detecting acute COPD exacerbations (AECOPD) in healthcare claims and estimate costs associated with AECOPD over a 12-month period. Commercial and Medicare Advantage healthcare plan members (≥40 years old) with evidence of COPD were identified from US healthcare-claims database. To refine the algorithm detecting AECOPD in claims data, sensitivity and positive-predictive value calculations were performed to compare AECOPD identification in healthcare claims versus medical charts. Analyses were also performed to examine total exacerbation-related costs for events identified with the new claims algorithm plus events missed. The final algorithm had a sensitivity of 84.9%, with a positive-predictive value of 67.5%. Medical records were abstracted for 402 patients. In the overall sample of healthcare claims (n = 243,998), the algorithm detected ≥1 AECOPD event in 61.3% of patients. The mean cost per patient during an AECOPD episode, identified by the final algorithm, was USD 6,760 (n = 301), with an incremental average cost of USD 607 (n = 122) to 'unobserved' episodes (not reported in claims data) among the chart sample. After multivariate modeling, predicted yearly exacerbation costs translated to USD 1.12 billion per 100,000 patients (USD 12,000 per patient), with 35.76 million associated with unobserved exacerbations. While the final algorithm warrants further validation and study, these findings highlight unobserved AECOPD and their economic burden.

Cross-sectional survey study to examine underuse of twice daily inhaled maintenance therapy among patients with asthma.

Objective: Anecdotal evidence suggests that some patients with asthma intentionally use their twice-daily (BID) inhaled controller therapy once daily (QD), thus not achieving optimal dosing levels. This study identified the prevalence of and factors associated with intentional QD use of BID-indicated controllers among adult patients with asthma. Methods: This was a cross-sectional survey study of adults using inhaled controllers intended for BID dosing for treatment of asthma and/or COPD. Survey responses were linked to administrative claims data for the prior 12 months (baseline). Results of patients indicating both an asthma diagnosis and current intentional QD or BID use of controllers are presented. Results: Of 1401 patients with asthma, 30.9% reported intentional QD use of their controller and 69.1% reported BID use. Intentional QD use was mostly a function of patients' lack of perceived need for BID treatment (44.1%) or physician orders to take their controller QD (34.0%). Patients reporting intentional QD use tended to be healthier (higher health status scores, and lower Charlson comorbidity scores, ambulatory and ER visits, and healthcare costs) with better asthma control (lower asthma-related ER and ambulatory visits and rescue medication use, and higher Asthma Control Test scores) compared with patients reporting BID use. Conclusions: Perceptions regarding health and the necessity of controller use to control or treat asthma were the main drivers of medication-taking behavior. Patients with less severe asthma were more likely to report once daily use of their inhaled controller, but still maintained asthma control.

Assessment of symptom burden and adherence to respiratory medications in individuals self-reporting a diagnosis of COPD within a community pharmacy setting.

OBJECTIVES: Data on symptom burden or medication adherence in patients with chronic obstructive pulmonary disease (COPD) within a community pharmacy setting are limited. This study assessed symptom burden and adherence to respiratory medications in individuals reporting COPD, chronic bronchitis, or emphysema diagnoses visiting community pharmacies. DESIGN: This cross-sectional study enrolled participants visiting 35 community pharmacies in Missouri (October 2016 to April 2017). PARTICIPANTS: Eligible participants (aged 40 years or more with a self-reported history of COPD, prescription for at least 1 COPD maintenance medication during the previous 12 months, and able to complete an English questionnaire) were identified from pharmacy dispensing records. MAIN OUTCOME MEASURES: Participants completed a questionnaire assessing demographics, clinical characteristics, health literacy, COPD Assessment Test (CAT) modified Medical Research Council (mMRC) dyspnea scale scores, and exacerbation history. Recent spirometry data were obtained, if available, from participants' physicians. COPD was classified according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2016 criteria. Medication adherence was assessed as proportion of days covered (PDC) from dispensing records. RESULTS: Of 682 participants (mean age 63.0 years; 57% female) with available pharmacy data, 251 (36.8%) had available spirometry data. Most participants had mMRC scores ≥ 2 (60.9%) and CAT scores ≥ 10 (90.2%); 57.2% reported at least 2 moderate or 1 or more severe exacerbations within the previous 12 months. GOLD classifications varied depending on the scale used (mMRC vs. CAT); more participants were classified as group C/D than group A/B, with the highest proportion classified as group D (higher symptom burden and exacerbation risk). Mean PDC was 0.46 ± 0.37; only 28.7% of participants were adherent (PDC ≥ 80%) to at least 1 COPD maintenance medication. CONCLUSION: Individuals self-reporting a COPD diagnosis receiving respiratory medications from community pharmacies in Missouri have a high symptom burden and low medication adherence. Further research should determine reasons for low adherence and ways to reduce COPD symptoms.

A Randomized Clinical Trial Comparing the ELLIPTA and HandiHaler Dry Powder Inhalers in Patients With COPD: Inhaler-Specific Attributes and Overall Patient Preference.

This randomised, open-label, cross-over, placebo-containing inhaler study assessed patient preference indicators for ELLIPTA and HandiHaler dry powder inhalers in patients with COPD (NCT02786927; GSK identifier: 204983). The primary objective of this study was to assess patient preference between ELLIPTA and HandiHaler based on the number of steps needed to use the inhaler. Eligible patients ≥40 years of age with COPD were randomised 1:1 to receive their current COPD medication plus a placebo-containing ELLIPTA or HandiHaler inhaler once daily for 7 ± 2 days (treatment period 1); this was followed by a 7 ± 2-day placebo treatment with the alternative inhaler. A 5-item questionnaire assessed inhaler-related patient preferences. A total of 212 patients (mean age, 65.1 years) were enrolled at 22 US sites; 73% had a COPD duration ≥5 years. Median (range) exposure was 8 ( 5 , 13 ) days for ELLIPTA and 8 ( 1 , 16) days for HandiHaler. Significantly more patients preferred ELLIPTA to HandiHaler in terms of the number of steps to use and all secondary attributes (size, comfort of the mouthpiece, remaining doses, and ease of use of the two inhalers; all p < 0.001). Similar results were observed irrespective of the order of inhaler use. Eighteen patients (8%) reported at least one AE and two (<1%) patients reported four non-fatal SAEs; none were related to the study treatment. Patient attitude toward a particular inhaler and their experiences in using it can affect adherence to therapy, which can in turn strongly influence effectiveness of inhaled medications. This study uses a robust methodology to assess patient preference.

Characteristics and health care resource use of subjects with COPD in the year before initiating LAMA monotherapy or LAMA+LABA combination therapy: A U.S. database study.

PURPOSE: To characterize subjects with chronic obstructive pulmonary disease (COPD) newly initiated on long-acting muscarinic antagonists (LAMA) or dual LAMA/long-acting ß2-adrenergic agonist (LABA) therapy. DESIGN: This pilot/preliminary analysis was a retrospective crosssectional study of subjects with COPD from the Optum Impact National Managed Care Benchmark Database. METHODOLOGY: Subjects with at least one LAMA prescription in the index period (July 2008-June 2009) were included and stratified by treatment. Data were collected in the year before the index date and included comorbidities, medication use, COPD-related costs, health care resource use, and exacerbations. RESULTS: Of 5,311 eligible subjects, 2,057 initiated LAMA therapy (LAMA cohort) and 191 initiated LAMA+LABA therapy (LAMA+LABA cohort). The Charlson comorbidity index was slightly lower in the LAMA+LABA cohort than the LAMA cohort (mean±SD: 0.63±1.13 vs. 0.66±1.28), but the number of prescriptions was higher (mean±SD: 42.9±23.2 vs. 30.5±27.2). The LAMA+LABA cohort had higher short-acting inhaled ß2 agonist (56.0% vs. 35.7%), oral corticosteroid (37.7% vs. 32.6%), and home oxygen therapy use (14.1% vs. 3.2%) than the LAMA cohort. Total medical costs were greater in the LAMA+LABA cohort than the LAMA cohort (mean±SD: $3,320.40±4085.9 vs. $1,226.20±3602.9), although emergency department ($11.00±66.8 vs. $30.70±259.2) and outpatient visit ($39.60±163.1 vs. $41.70±424.3) costs were lower. Resource use and exacerbation incidence were similar between cohorts. CONCLUSION: In this first look, subjects with COPD initiating LAMA or LAMA+LABA therapy exhibited different clinical and resource use characteristics in the year before treatment. Subjects receiving LAMA+LABA were older, with higher COPD co-medication use, more prescriptions, and associated higher pharmacy costs compared with subjects initiating LAMA. These differences may reflect a higher severity of COPD in those starting LABA+LAMA treatment.

A Preference Study of Two Placebo Dry Powder Inhalers in Adults with COPD: ELLIPTA® Dry Powder Inhaler (DPI) versus DISKUS® DPI.

Patients' preference is an important factor in selecting an inhaler treatment for COPD. The DISKUS® dry powder inhaler (DPI), which has been available to deliver several COPD medications for a decade, and the ELLIPTA® DPI, developed for the delivery of newer once-daily medications for patients with COPD, were studied in terms of patient preference and inhaler-specific attributes. We conducted a randomized, open-label, crossover study in patients with COPD. Patients used placebo ELLIPTA DPI once daily and placebo DISKUS DPI twice daily, for ∼1 week each, while continuing their COPD medications. Endpoints were: inhaler preference based on size of the numbers on the dose-counter (primary); the number of steps needed and inhaler size (secondary); and based on comfort of the mouthpiece, ease of opening, overall preference, and dosing regimen preference ('other'). Safety assessments included adverse events (AEs). A total of 287 patients were randomized. A significantly (p < 0.001) larger proportion of patients preferred the ELLIPTA DPI over DISKUS DPI for each of the tested attributes and overall, and preferred once-daily over twice-daily dosing. AEs were reported for 36 patients (13%); one (dry mouth) was considered to be related to the placebo-containing DISKUS DPI. Three patients had five non-fatal serious AEs, none were deemed inhaler-related. This study demonstrated that more patients with COPD preferred five specific inhaler attributes of the ELLIPTA DPI over DISKUS DPI and overall, and preferred once-daily versus twice-daily dosing. Safety profiles were consistent with those expected for COPD.

Health-care utilization and costs with fluticasone propionate and fluticasone propionate/salmeterol in asthma patients at risk for exacerbations.

Although studies have established that adding long-acting beta agonists (LABA) to inhaled corticosteroid (ICS) monotherapy among patients with inadequately controlled asthma is associated with better outcomes than increasing ICS dosage, outcomes with ICS versus fixed-dose ICS/LABA combination among patients with recent asthma exacerbation or frequent use of rescue medication are unavailable. This study was designed to compare health-care utilization/costs among patients with recent asthma exacerbation or frequent rescue medication use who received fluticasone propionate (FP) alone versus fixed-dose FP/salmeterol combination (FSC). A retrospective cohort study was conducted using a large health insurance data set. Patients with one or more claims with asthma diagnosis, two or more prescriptions for FSC (250/50- or 100/50-mg formulations) or FP (220- or 110-mg formulations), and one or more asthma exacerbations or five or more short-acting beta agonist (SABA) prescriptions within 1 year before initial receipt of study medications were included. Health-care utilization/costs and controller therapy compliance were compared for patients receiving FSC versus FP using multivariate regression analysis controlling for FP dose and baseline characteristics. A total of 7779 patients met inclusion criteria (5769, FSC, and 2010, FP) with comparable mean follow-up (FSC, 685 days; FP, 670 days; p = 0.151). Controlling for FP dosage and baseline characteristics, FSC patients had lower risks of asthma-related exacerbations, fewer SABAs and systemic corticosteroids, higher costs of asthma medications and total asthma-related health care, and lower total asthma-related health-care costs excluding study medication cost. In asthma patients with recent exacerbation or frequent SABA use, receipt of FSC reduced asthma-related exacerbation risks and rescue medication use versus receipt of FP.

Reliability, validity, and responsiveness of the Rhinitis Control Assessment Test in patients with rhinitis.

BACKGROUND: The Rhinitis Control Assessment Test (RCAT) is a brief, patient-completed tool to evaluate rhinitis symptom control. OBJECTIVE: We sought to test the reliability, validity, and responsiveness of RCAT and to estimate a cut-point score and minimal important difference (MID). METHODS: A total of 402 patients 12 years of age and older with allergic or nonallergic rhinitis were enrolled in a noninterventional study. Patients completed the RCAT (6 items; score range, 6-30) and had Total Nasal Symptom Scores (TNSSs) measured at baseline and 2 weeks later. Physicians completed a global assessment of rhinitis symptom control (Physician's Global Assessment) and disease severity. Internal consistency, test-retest reliability, convergent validity, known-groups validity, and responsiveness were evaluated. The MID was determined by using distribution- and anchor-based methods. Content validity of the RCAT was assessed in individual interviews with a separate group of 58 adult patients. RESULTS: Internal consistency and test-retest reliability of RCAT scores were 0.77 and 0.78, respectively. Convergent validity correlation between RCAT and TNSS scores was 0.57, and that between RCAT and Physician's Global Assessment scores was 0.34. Mean RCAT scores differed significantly (P < .001) across patient groups, differing in TNSS (F = 72.7), Physician's Global Assessment score (F = 28.6), and disease severity (F = 34.1) in the hypothesized direction. Results suggested a cut-point score of 21 or less can be used to identify patients who are experiencing rhinitis symptom control problems. The preliminary estimate of the MID was 3 points. Patients found RCAT items comprehensive, easy to understand, and relevant. CONCLUSION: The RCAT demonstrated adequate reliability, validity, and responsiveness and was deemed acceptable and appropriate by patients. This tool can facilitate the detection of rhinitis symptom control problems, and its brevity supports its usefulness in clinical care.

Hereditary factor X deficiency in America survey: impact on quality of life and burden of disease in patients and caregivers.

Hereditary factor X deficiency (HFXD) is a rare bleeding disorder causing delayed haemostasis and potentially life-threatening bleeds. Patient/caregiver burden and diagnosis path have not been well characterized. THE AIM OF THIS STUDY WAS TO: describe the diagnosis path, disease burden, and HFXD impact on quality of life (QoL) in patients and caregivers.This was a prospective, cross-sectional, web-based survey of patients with HFXD and caregivers addressing the patient/caregiver experience, QoL, humanistic and unmet needs.Thirty patients and 38 caregivers completed the survey with mean ages 24.7 and 44.6 years, respectively. Mean age at diagnosis was 4.1 years. The diagnostic process was somewhat/very difficult for 23% of patients and 26% of caregivers. Approximately half (53%) received single factor replacement (SFR) as prophylaxis or on-demand. Most patients (71%) reported regular prophylaxis treatment. Over one-fourth (27%) reported treatment with fresh frozen plasma. Bleeding episodes were less common in patients using SFR versus non-SFR: three bleeds or fewer were reported by 92% SFR and 75% non-SFR patients. HFXD patients reported low well being in work/school/social activities with mean HFXD-adapted Hemophilia Well being Index. Patient symptoms negatively impacted caregiver burden with a mean HFXD-adapted Hemophilia Caregiver Index (±SD) of 15.9 (4.6), but also unexpectedly had a positive impact on self-worth and inner strength.To our knowledge, this is the first study to assess patient and caregiver burden of HFXD and impact on QoL. Improvements in symptom recognition, prompt diagnosis, and adherence to expert recommendations for treatment could improve QoL and decrease burden on HFXD patients and caregivers.

Risk of asthma exacerbation, asthma-related health care utilization and costs, and adherence to controller therapy in patients with asthma receiving fluticasone propionate/salmeterol inhalation powder 100 µg/50 µg versus mometasone furoate inhalation powder.

OBJECTIVE: National asthma treatment guidelines recommend low/medium-dose inhaled corticosteroids (ICSs) as initial therapy in mild asthma patients. However, low doses of a fixed-dose combination of ICS and long-acting ß-agonists are sometimes used. This study compares asthma-related outcomes and health care utilization and costs in clinical practice in patients starting fluticasone propionate 100 µg and salmeterol 50 µg via Diskus (FSC) or mometasone furoate (MF). METHODS: A retrospective cohort study was conducted to compare asthma-related outcomes in asthma patients who received FSC or MF, using a large health insurance claims dataset spanning January 2004-December 2008. Patients with ≥1 claim with an asthma ICD-9-CM diagnosis code and ≥2 FSC or MF prescriptions were included, stratified into FSC or MF groups by study drug received first and matched using propensity score. RESULTS: A total of 18,283 patients met inclusion criteria (14,044 FSC and 4239 MF); 3799 matched pairs were identified (mean follow-up: FSC 548 days, MF 537 days). FSC patients had lower risk of asthma-related exacerbation (Hazard ratio = 0.88, 95% CI 0.81-0.95, p = .002), defined as either asthma-related emergency department (ED) visits/hospitalizations or receipt of systemic corticosteroids (SCSs); fewer SCS claims (mean 0.28 vs. 0.33, p = .021); and fewer asthma-related physician office (PO) and hospital outpatient (HO) visits (mean 1.17 vs. 1.63, p < .001). However, asthma-related ED visits were higher with FSC (p = .004), and FSC patients had higher total costs of asthma-related health care ($953 vs. $862, p = .002). CONCLUSIONS: In asthma patients initiating ICS therapy, MF had lower asthma-related ED visits. However, FSC may reduce the use of SCS and asthma-related PO/HO visits.

RDS-NExT workshop: consensus statements for the use of surfactant in preterm neonates with RDS.

OBJECTIVE: To provide the best clinical practice guidance for surfactant use in preterm neonates with respiratory distress syndrome (RDS). The RDS-Neonatal Expert Taskforce (RDS-NExT) initiative was intended to add to existing evidence and clinical guidelines, where evidence is lacking, with input from an expert panel. STUDY DESIGN: An expert panel of healthcare providers specializing in neonatal intensive care was convened and administered a survey questionnaire, followed by 3 virtual workshops. A modified Delphi method was used to obtain consensus around topics in surfactant use in neonatal RDS. RESULT: Statements focused on establishing RDS diagnosis and indicators for surfactant administration, surfactant administration methods and techniques, and other considerations. After discussion and voting, consensus was achieved on 20 statements. CONCLUSION: These consensus statements provide practical guidance for surfactant administration in preterm neonates with RDS, with a goal to contribute to improving the care of neonates and providing a stimulus for further investigation to bridge existing knowledge gaps.

Short-acting ß-agonist use and its ability to predict future asthma-related outcomes.

BACKGROUND: Short-acting ß-agonist (SABA) use is well established in predicting asthma events in adults. However, this predictive ability has yet to be established in a pediatric population together with an assessment of amount of use. OBJECTIVE: To identify the number of SABA canisters that best predicts future asthma-related exacerbations and the optimal length of time for measurement of SABA use in pediatric and adult asthma patients. METHODS: Asthma patients were identified from a Medicaid and a commercially insured database (January 1, 2004, through December 31, 2005, and January 1, 2004, through June 30, 2006, respectively). Following the date of first asthma medication, an assessment period (3, 6, or 12 months) was used to measure SABA use. Asthma-related exacerbations were identified in the subsequent 12-month period. Receiver operating characteristic curve analyses and logistic regression were used to select the critical values of SABA use and optimal assessment periods and to conduct incremental analysis, respectively. RESULTS: A total of 33,793 Medicaid and 101,437 commercial patients met the study criteria. Use of 3 or more SABA canisters during 12 months was identified in both pediatric Medicaid and commercial populations to best predict an increased risk of an asthma-related exacerbation. For adults, use of 2 or more SABA canisters was found as the critical value with shorter optimal assessment periods of 3 and 6 months. Each additional SABA canister resulted in an 8% to 14% and 14% to 18% increase in risk of an asthma-related exacerbation in children and adults, respectively. CONCLUSION: The study identified critical values of SABA use that predict future asthma events. Each additional SABA canister predicted increases in exacerbation risk in children and adults.

Retrospective comparison of early versus late treatment with fluticasone propionate/salmeterol after an asthma exacerbation.

BACKGROUND: The benefits of inhaled corticosteroids in asthma are well established. Early use of inhaled anti-inflammatories following and exacerbation could be beneficial. METHODS: A retrospective observational cohort study compared the risk of asthma-related exacerbations [hospitalization, emergency department visit, and/or treatment with systemic corticosteroid] in patients receiving treatment with fluticasone propionate/salmeterol in a single inhaler (FSC) within 90 days following an initial asthma-related exacerbation (early treatment) versus patients receiving the treatment subsequently (late treatment). Data were from a large health insurance claims database spanning from January 1998 to April 2008. Subjects included patients with ≥1 prescription for FSC ≤ 1 year after first asthma-related exacerbation. Patients with early treatment were matched to those with late treatment by propensity score and compared in terms of healthcare utilization and costs after initiation of FSC. RESULTS: A total of 14,861 patients met study inclusion criteria, including 10,793 early and 4068 late treatment patients. After matching, 3555 pairs were well matched on all pretreatment characteristics and duration of follow-up (mean 722 vs. 717 days, p = .634). Early versus late treatment was associated with longer time to first asthma-related exacerbation (hazard ratio = 0.82, 95% CI 0.75-0.88, p < .001), fewer short-acting ß-agonists prescriptions (3.3 vs. 3.6, p = .031), higher outpatient yearly per patient pharmacy costs ($1320 vs. $1163, p = .008), and lower yearly per patient asthma-related emergency department visit costs ($80 vs. $105, p = .032). Total yearly per patient asthma-related costs were similar ($2197 vs. $2064, p = .203). CONCLUSIONS: Earlier use of FSC following an asthma exacerbation was associated with reduced risk of future asthma-related exacerbation and lower use of rescue medications.

Development and validation of a drug adherence index for COPD.

BACKGROUND: Inhaled medications are the mainstay of treatment for chronic obstructive pulmonary disease (COPD). Despite their importance, adherence to these medications is low. Low adherence is linked to increased exacerbation rates, mortality rates, health care utilization, and, ultimately, increased costs. A drug adherence index (DAI) is a predictive modeling tool that identifies patients most likely to change adherence status so that they can be targeted for support programs. Optum has previously developed DAI tools for diabetes, hypertension, and high cholesterol. In this study, a COPD-specific DAI was developed. This DAI tool could be used to better target medication adherence support in patients with COPD, aiming to increase adherence. OBJECTIVES: To develop a COPD-specific DAI using (a) enrollment, medical, and pharmacy variables and (b) only enrollment and pharmacy variables for potential application to pharmacy benefit managers and pharmacy plans. METHODS: This was a retrospective observational study using health care claims among Medicare Advantage with Part D beneficiaries with COPD in the United States. Potential predictors of adherence were measured during a 1-year baseline period. The adherence outcome was measured during a subsequent 1-year at-risk period. Adherence to long-acting bronchodilators was defined as a proportion of days covered (PDC) ≥80%. Nonadherence was defined as a PDC of <80%. Patients were stratified according to their adherence status at baseline, and logistic regression models were developed separately for each set of patients. Separate models were also developed using enrollment, medical, and pharmacy variables (primary objective) or using enrollment and pharmacy variables only (secondary objective). RESULTS: A total of 61,507 patients met all inclusion and exclusion criteria. For the primary objective, at baseline, 31,142 patients were adherent and 30,365 patients were nonadherent. The final DAI model used to predict future nonadherence included 30 covariates, with 7 predictors from medical claims. The validated model c-statistic was 0.752. The final DAI model used to predict future adherence included 29 covariates; only 4 predictors were from medical claims. The validated model c-statistic was 0.691. Findings were similar for the secondary objective using only enrollment and pharmacy variables. CONCLUSIONS: This DAI was developed and validated specifically to predict future adherence status to long-acting bronchodilator medications among patients with COPD. The DAI models performed better for predicting nonadherence than predicting adherence. Both organizations with medical and pharmacy data and organizations with only pharmacy data could utilize the DAI tool to target patients for adherence programs, as results were similar with and without the use of medical variables. DISCLOSURES: This study was sponsored and funded by GlaxoSmithKline (HO-16-17938). The study sponsor participated in the conception and design of the study, analysis and interpretation of the data, and drafting and critical revision of the report and approved submission of the manuscript. All authors had access to the results of the analyses, reviewed and edited the manuscript, approved the final draft, and were involved in the decision to submit the manuscript for publication. The data contained in the Optum database contain proprietary elements owned by Optum and, therefore, cannot be broadly disclosed or made publicly available at this time. The disclosure of these data to third parties assumes certain data security and privacy protocols are in place and that the third party has executed a license agreement that includes restrictive agreements governing the use of the data. Bengtson, Buikema, and Bankcroft are employees at Optum, and Schilling is a former employee of Optum; their employment was not contingent on this work. Optum was funded by GlaxoSmithKline to conduct the study. Stanford was an employee of GlaxoSmithKline at the time of this study and holds stock in GlaxoSmithKline.