Dual-combination maintenance inhaler preferences in asthma and chronic obstructive pulmonary disease: A patient-centered benefit-risk assessment.

BACKGROUND: A variety of dual-combination maintenance inhalers are used to treat asthma and chronic obstructive pulmonary disease (COPD). Understanding patient preferences for treatment attributes may help select an optimal treatment from the patient perspective. METHODS: Patient preferences for maintenance inhaler device and medication attributes were elicited through a discrete choice experiment and used in benefit-risk assessments to calculate predicted choice probabilities (PrCPs) for 14 dual-combination maintenance inhalers in four treatment classes: lower- and higher-dose inhaled corticosteroid (ICS)/long-acting beta agonist (LABA) inhalers for asthma, and ICS/LABA and long-acting muscarinic antagonist (LAMA)/LABA inhalers for COPD. RESULTS: For all treatment classes, reduced exacerbations and faster onset of action were the most important attributes. For all classes, patients were willing to tolerate an extra yearly exacerbation to decrease the medication's onset of action from 30 to 5 min. For patients with asthma using lower-dose ICS/LABA (n = 497), budesonide/formoterol fumarate dihydrate (80 µg/4.5 µg) pressurized metered-dose inhaler (pMDI) had the highest PrCP (28.4%), and for those using a higher-dose ICS/LABA (n = 285), PrCPs were highest for mometasone furoate/formoterol fumarate dihydrate (200 µg/5 µg) pMDI (27.0%) and budesonide/formoterol fumarate dihydrate (160 µg/4.5 µg) pMDI (26.9%). For patients with COPD using an ICS/LABA (n = 574), budesonide/formoterol fumarate dihydrate (160 µg/4.5 µg) pMDI had the highest PrCP (56.6%), and for those using a LAMA/LABA inhaler (n = 217), tiotropium/olodaterol (2.5 µg/2.5 µg) soft mist inhaler had the highest PrCP (42.3%). CONCLUSIONS: Patient preference data for maintenance inhaler attributes can be used to identify a preference order of inhalers in different treatment classes.

Medication Discontinuation in Adults With COPD Discharged From the Hospital: A Population-Based Cohort Study.

BACKGROUND: Patients admitted to the hospital with COPD are commonly managed with inhaled short-acting bronchodilators, sometimes in lieu of the long-acting bronchodilators they take as outpatients. If held on admission, these long-acting inhalers should be re-initiated upon discharge; however, health-care transitions sometimes result in unintentional discontinuation. RESEARCH QUESTION: What is the risk of unintentional discontinuation of long-acting muscarinic antagonist (LAMA) and long-acting beta-agonist and inhaled corticosteroid (LABA-ICS) combination medications following hospital discharge in older adults with COPD? STUDY DESIGN AND METHODS: A retrospective cohort study was conducted by using health administrative data from 2004 to 2016 from Ontario, Canada. Adults with COPD aged ≥ 66 years who had filled prescriptions for a LAMA or LABA-ICS continuously for ≥ 1 year were included. Log-binomial regression models were used to determine risk of medication discontinuation following hospitalization in each medication cohort. RESULTS: Of the 27,613 hospitalization discharges included in this study, medications were discontinued 1,466 times. Among 78,953 patients with COPD continuously taking a LAMA or LABA-ICS, those hospitalized had a higher risk of having medications being discontinued than those who remained in the community (adjusted risk ratios of 1.50 [95% CI, 1.34-1.67; P < .001] and 1.62 [95% CI, 1.39, 1.90; P < .001] for LAMA and LABA-ICS, respectively). Crude rates of discontinuation for people taking LAMAs were 5.2% in the hospitalization group and 3.3% in the community group; for people taking LABA-ICS, these rates were 5.5% in the hospitalization group and 3.1% in the community group. INTERPRETATION: In an observational study of highly compliant patients with COPD, hospitalization was associated with an increased risk of long-acting inhaler discontinuation. These Results suggest a likely larger discontinuation problem among less adherent patients and should be confirmed and quantified in a prospective cohort of patients with COPD and average compliance. Quality improvement efforts should focus on safe transitions and patient medication reconciliation following discharge.

Trends and Factors Associated with Nebulized Therapy Prescription in Older Adults with Chronic Obstructive Pulmonary Disease from 2008 to 2015.

Background: Medical management of patients with chronic obstructive pulmonary disease (COPD) includes nebulized therapy as an option for inhalational drug delivery. A broad variety of short- and long-acting bronchodilators and inhaled corticosteroids in the nebulized form are available. Despite this, limited information exists on the pattern and predictors of nebulized prescription. We examined the trend and factors associated with prescription of nebulized therapy among Medicare beneficiaries with COPD. Methods: A retrospective cross-sectional study of 5% Medicare beneficiaries with COPD (n = 66,032) who were enrolled in parts A, B, and D and received nebulized prescription from 2008 to 2015 was conducted. This sample has shown to be representative of the entire fee-for-service Medicare population. The primary outcome was a prescription of nebulized medications. Reliever nebulized medications included short-acting beta agonist (SABA), short-acting muscarinic agents (SAMAs), and a combination of SABA and SAMA, while maintenance nebulized medications included long-acting beta agonists, long-acting muscarinic agents, and corticosteroid solutions as well as combinations of these agents. The secondary outcome was prescription of other inhaler respiratory medications not administered with a nebulizer. Results: Overall, 38.9% patients were prescribed nebulized medication and their prescription significantly declined from 42.4% in 2008 to 35.1% in 2015, majority of which was related to decreased prescriptions of nebulized relievers. Factors associated with the prescription of nebulized medications include female gender (odds ratio [OR] = 1.06; 95% confidence interval [CI] = 1.02-1.09), dual eligibility or low-income subsidy beneficiaries (OR = 1.49; CI = 1.44-1.53), hospitalization for COPD in the previous year (OR = 1.29; CI = 1.25-1.34), home oxygen therapy (OR = 2.29; CI = 2.23-2.36), pulmonary specialist visit (OR = 1.24; CI = 1.20-1.27), and moderate (OR = 1.61; CI = 1.57-1.65) or high (OR = 1.52; CI = 1.46-1.59) severity of COPD. Conclusion: Between 2008 and 2015, prescriptions for nebulized therapy for COPD declined among Medicare beneficiaries, probably related to increase in use of maintenance non-nebulized medications.

Reducing pediatric asthma hospital length of stay through evidence-based quality improvement and deployment of computerized provider order entry.

Objective: Evaluate the impact of multi-component quality improvement for pediatric asthma care focusing on serial use of an evidence-based clinical pathway via paper order sets, pathway integration into computerized provider order entry (CPOE), use of a clinical respiratory score (CRS) and a discharge checklist. Methods: Outcomes were assessed over three intervention periods and 50 months on: time to beta-agonist and steroid first administration, frequency of readmissions and hospital length of stay. A general linear model estimated mean log(LOS) over time and between study periods. Time to discharge was transformed using the natural logarithm. Results: No improvements in time to first beta-agonist or steroid administration were observed. There was a reduction in 100-day readmissions (p = 0.008): decreasing from 7.4 to 2.1% after introduction of paper order sets and CRS (adjusted p = 0.04); to 3.9% after CPOE implementation (adjusted p = 0.53) and to 2.2% when a discharge checklist was added (adjusted p = 0.01). There was a statistically significant reduction in LOS between study periods (p = 0.015). The geometric mean LOS in hours during study periods 1-4 were: 34.8 (95% CI: 32.2, 37.6), 29.3 (95% CI: 27.5, 31.3), 29.0 (95% CI: 27.0, 31.3) and 23.1 (95% CI: 22.1, 24.2). Pair-wise comparisons between periods were statistically significant (adjusted p ≤ 0.003), except for Periods 2 and 3 (adjusted p = 0.83). Conclusions: Hospital length of stay and 100-day readmissions rate in a predominantly Hispanic, Medicaid patient population were reduced by utilization of an evidence-based best practices asthma management pathway and CRS within CPOE, combined with a checklist to expedite discharge.

Cost saving of switching to equivalent inhalers and its effect on health outcomes.

BACKGROUND: Switching inhalers to cheaper equivalent products is often advocated as a necessary cost saving measure, yet the impact on patient's health and healthcare utilisation has not been measured. METHODS: We identified asthma and chronic obstructive pulmonary disease (COPD) patients from UK primary care electronic healthcare records between 2000 and 2016. A self-controlled case series was used to estimate incidence rate ratios (IRR); comparing outcome rates during the risk period, 3 months after the exposure (financially motivated switch), and control periods (preswitch and postrisk period). Four outcomes were assessed: disease exacerbation, general practitioner consultation, non-specific respiratory events and adverse-medication events. Medication possession ratio (MPR) was calculated to assess adherence. 2017 National Health Service indicative prices were used to estimate cost differences per equivalent dose. RESULTS: We identified a cohort of 569 901 asthma and 171 231 COPD regular inhaler users, 2% and 6% had been switched, respectively. Inhaler switches between a brand-to-generic inhaler, and all other switches (brand-to-brand, generic-to-generic, generic-to-brand), were associated with reduced exacerbations (brand-to-generic: IRR=0.75, 95% CI 0.64 to 0.88; all other: IRR=0.79, 95% CI 0.71 to 0.88). Gender, age, therapeutic class, inhaler device and inhaler-technique checks did not significantly modify this association (p<0.05). The rate of consultations, respiratory-events and adverse-medication events did not change significantly (consultations: IRR=1.00, 95% CI 0.99 to 1.01; respiratory-events: IRR=0.96, 95% CI 0.95 to 0.97; adverse-medication-events: IRR=1.05, 95% CI 0.96 to 1.15). Adherence significantly increased post-switch (median MPR: pre-switch=54%, post-switch=62%; p<0.001). Switching patients, in the cohort of regular inhaler users, to the cheapest equivalent inhaler, could have saved around £6 million annually. CONCLUSION: Switching to an equivalent inhaler in patients with asthma or COPD appeared safe and did not negatively affect patient's health or healthcare utilisation.

Medication adherence and persistence in chronic obstructive pulmonary disease patients receiving triple therapy in a USA commercially insured population.

INTRODUCTION: This longitudinal, retrospective cohort study of patients with COPD describes baseline characteristics, adherence, and persistence following initiation of inhaled corticosteroids (ICS)/long-acting ß2-agonists (LABA)/long-acting muscarinic antagonists (LAMA) from multiple inhaler triple therapy (MITT). METHODS: Patients aged ≥40 years receiving MITT between January 2012 and September 2015 were identified from the IQVIA™ Real-world Data Adjudicated Claims-USA database. MITT was defined as subjects with ≥1 overlapping days' supply of three COPD medications (ICS, LABA, and LAMA). Adherence (proportion of days covered, PDC) and discontinuation (defined as a gap of 1, 30, 60, or 90 days of supply in any of the three components of the triple therapy) were calculated for each patient over 12 months of follow-up. In addition, analyses were stratified by number of inhalers. RESULTS: In total, 14,635 MITT users were identified (mean age, 62 years). Mean PDC for MITT at 12 months was 0.37%. Mean PDC for the ICS/LABA and LAMA component at 12 months was 49% (0.49±0.31; median, 0.47) and 54% (0.54±0.33; 0.56), respectively. The proportion of adherent patients (PDC ≥0.8) at 12 months was 14% for MITT. Allowing for a 30-day gap from last day of therapy, 86% of MITT users discontinued therapy during follow-up. CONCLUSION: Patients with COPD had low adherence to and persistence with MITT in a real-world setting. Mean PDC for each single inhaler component was higher than the mean PDC observed with MITT. Reducing the number of inhalers may improve overall adherence to intended triple therapy.

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.

Predictors of inappropriate and excessive use of reliever medications in asthma: a 16-year population-based study.

BACKGROUND: Understanding factors associated with the inappropriate or excessive use of short-acting beta agonists (SABA) can help develop better policies. METHODS: We used British Columbian (BC)'s administrative health data (1997-2014) to create a retrospective cohort of asthma patients aged between 14 and 55 years. The primary and secondary outcomes were, respectively, inappropriate and excessive use of SABA based on a previously validated definition. Exposures were categorised into groups comprising socio-demographic variables, indicators of type and quality of asthma care, and burden of comorbid conditions. RESULTS: 343,520 individuals (56.3% female, average age 30.5) satisfied the asthma case definition, contributing 2.6 million person-years. 7.3% of person-years were categorised as inappropriate SABA use and 0.9% as excessive use. Several factors were associated with lower likelihood of inappropriate use, including female sex, higher socio-economic status, higher continuity of care, having received pulmonary function test in the previous year, visited a specialist in the previous year, and the use of inhaled corticosteroids in the previous year. An asthma-related outpatient visit to a general practitioner in the previous year was associated with a higher likelihood of inappropriate SABA use. Similar associations were found for excessive SABA use with the exception that visit to respirologist and the use of systemic corticosteroids were associated with increased likelihood of excessive use. CONCLUSIONS: Despite proven safety issues, inappropriate SABA use is still prevalent. Several factors belonging to patients' characteristics and type/quality of care were associated with inappropriate use of SABAs and can be used to risk-stratify patients for targeted attempts to reduce this preventable cause of adverse asthma outcomes.

Pharmacist-managed short-acting beta agonist refill service in a general pediatric clinic.

OBJECTIVES: To use a pharmacist-managed short-acting beta agonist (SABA) service (1) to determine the patient's rationale for SABA refill requests, (2) to assess adherence to current controller therapy and current level of disease control, and (3) to characterize the pharmacist's recommendations made in response to a patient's SABA refill request. SETTING: An academic-based general pediatric clinic. PRACTICE DESCRIPTION: SABA overuse is a marker of increased morbidity and mortality in children with asthma. This article describes a pharmacist-managed SABA refill telephone service. PRACTICE INNOVATION: The pediatric ambulatory care pharmacy team assessed and authorized (or denied) all SABA refill requests, provided education, and facilitated appropriate follow-up using a telephone service. INTERVENTIONS: Upon receiving a patient-requested SABA refill, the pharmacist identified the reason for the SABA request, assessed asthma control, and determined adherence to daily controllers or spacer use, if applicable. Education was also provided. Data obtained were used to determine SABA refill approval. EVALUATION: Primary reasons for SABA refill request were for (1) current symptom management and (2) no refills remaining in the absence of symptoms. Forty-two (50%) SABA refill requests were eligible for refill per the clinic algorithm, yet 70% actually received a refill after assessment by the pharmacist. Asthma control was assessed as 26% well controlled, 38% not well controlled, and 36% very poorly controlled. Forty-eight percent of patients prescribed daily controller medications were deemed adherent. Spacers were used in 43 of 76 (56%) patients using metered dose inhalers. Education was provided to 82% of caregivers. Pharmacists facilitated asthma follow-up visits in 41 of 84 (49%) patients contacted, and 61% of those appointments were kept. CONCLUSIONS: Pharmacist management of a SABA refill telephone service provides an additional means for delivery of asthma education, facilitates follow-up asthma care, helps to identify patients at risk for increased morbidity and mortality due to the overuse of SABAs, and provides another mechanism for medication refills.

Asthma control and disease burden in patients with asthma and allergic comorbidities.

OBJECTIVE: To assess asthma control and associations with health-related quality of life (HRQoL) and economic outcomes among patients with asthma and allergic comorbidities treated with inhaled corticosteroids (ICS) and long-acting beta-agonists (LABA) combination therapy. METHODS: Data from the 2011-2013 US National Health and Wellness Survey were used to identify patients with asthma currently treated with ICS and LABA combination therapy (N = 1923). Patients were included if they self-reported a physician diagnosis of asthma and at least one allergic/asthma-related comorbid condition (e.g., nasal allergies, atopic dermatitis). Asthma Control Test scores categorized patients as very poorly (scores ≤ 15; 29.3%), not well (16-19; 25.1%), or well controlled (20-25; 45.7%). Outcomes included HRQoL (SF-36v2; SF-12v2), work productivity and activity impairment, healthcare utilization (HRU), and annual indirect and direct costs. Generalized linear models, controlling for covariates, examined whether outcomes differed by asthma control. RESULTS: Over half of the patients had very poorly or not well-controlled asthma (54.4%). Patients with very poorly controlled versus well-controlled asthma reported significantly greater decreases in HRQoL, greater overall work impairment, and higher HRU (all, p < 0.05). Very poorly controlled patients incurred over double the indirect costs and nearly one and a half times the direct and total costs of well-controlled patients. CONCLUSIONS: Increasing level of asthma control was related to improved HRQoL and lower costs. The considerably high prevalence of uncontrolled asthma among patients on ICS and LABA suggests poor treatment adherence or unmet needs in current treatment and may require step-up therapy in appropriate patients according to clinical guidelines.

Effect of Study Design on Sample Size in Studies Intended to Evaluate Bioequivalence of Inhaled Short-Acting ß-Agonist Formulations.

Pharmacodynamic studies that use methacholine challenge to assess bioequivalence of generic and innovator albuterol formulations are generally designed per published Food and Drug Administration guidance, with 3 reference doses and 1 test dose (3-by-1 design). These studies are challenging and expensive to conduct, typically requiring large sample sizes. We proposed 14 modified study designs as alternatives to the Food and Drug Administration-recommended 3-by-1 design, hypothesizing that adding reference and/or test doses would reduce sample size and cost. We used Monte Carlo simulation to estimate sample size. Simulation inputs were selected based on published studies and our own experience with this type of trial. We also estimated effects of these modified study designs on study cost. Most of these altered designs reduced sample size and cost relative to the 3-by-1 design, some decreasing cost by more than 40%. The most effective single study dose to add was 180 µg of test formulation, which resulted in an estimated 30% relative cost reduction. Adding a single test dose of 90 µg was less effective, producing only a 13% cost reduction. Adding a lone reference dose of either 180, 270, or 360 µg yielded little benefit (less than 10% cost reduction), whereas adding 720 µg resulted in a 19% cost reduction. Of the 14 study design modifications we evaluated, the most effective was addition of both a 90-µg test dose and a 720-µg reference dose (42% cost reduction). Combining a 180-µg test dose and a 720-µg reference dose produced an estimated 36% cost reduction.

Prescription of oral short-acting beta 2-agonist for asthma in non-resource poor settings: A national study in Malaysia.

OBJECTIVE: Use of oral short-acting beta 2-agonist (SABA) persists in non-resource poor countries despite concerns for its lower efficacy and safety. Utilisation and reasons for such use is needed to support the effort to discourage the use of oral SABA in asthma. This study examined the frequency of oral short-acting Beta 2-agonist (SABA) usage in the management of asthma in primary care and determined correlates of its usage. METHODS: Data used were from the 2014 National Medical Care Survey in Malaysia, a nationally representative survey of primary care encounters (weighted n = 325818). Using methods of analysis of data for complex surveys, we determined the frequency of asthma diagnosis in primary care and the rate of asthma medication prescription, which includes oral SABA. Multivariate logistic regression models were built to assess associations with the prescription of oral SABA. RESULTS: A weighted estimate of 9241 encounters presented to primary care with asthma in 2014. The mean age of the patients was 39.1 years. The rate of oral SABA, oral steroids, inhaled SABA and inhaled corticosteroids prescriptions were 33, 33, 50 and 23 per 100 asthma encounters, respectively. It was most commonly used in patients with the age ranged between 20 to less than 40 years. Logistic regression models showed that there was a higher odds of oral SABA usage in the presence of respiratory infection, prescription of oral corticosteroids and in the private sector. CONCLUSION: Oral SABA use in asthma is found to be common in a non- resource poor setting and its use could be attributed to a preference for oral medicines along undesirable clinical practices within a fragmented health system.

Basic Life Support Access to Injectable Epinephrine across the United States.

BACKGROUND: Aggressive epinephrine administration has growing support in the treatment of anaphylaxis, a life-threatening allergic reaction. Emergency Medical Services (EMS) providers are frequently in a position to provide the first care to someone experiencing an anaphylactic reaction. Intramuscular injection of epinephrine is the definitive pharmacologic treatment for many associated symptoms. While easy to use, epinephrine autoinjectors (EAI) are prohibitively expensive, having increased in price ten-fold in ten years. Some states and EMS departments have begun expanding the scope of practice to allow Basic Life Support (BLS) providers, previously restricted to noninvasive therapies, to administer epinephrine by syringe. OBJECTIVES: To compile a current and comprehensive list of how epinephrine is carried and used by EMS across the USA. METHODS: An online survey focusing on anaphylaxis protocols and epinephrine administration was sent to state EMS medical directors and officials in all 50 states. Follow-up telephone calls were made to ensure compliance. Data were analyzed with descriptive statistics. RESULTS: Forty-nine of the 50 states in the USA provided a survey response. Texas responded but declined to participate in the survey because of practice variability across the state. In the other states, the form of epinephrine allowed or required on BLS ambulances was consistent with the scope of practice of their Basic Emergency Medical Technician (EMT). Thirteen states had training programs to allow BLS providers to inject epinephrine; 7 were considering it; 29 were not. Twenty-seven states specified EAI as the only form of epinephrine required or allowed on their BLS ambulances. No states reported allowing any level of EMS provider below EMT to use alternatives to EAI. CONCLUSION: This study confirms that many states have expanded the training of BLS providers to include the use of syringe injectable epinephrine. Even so, the majority of states relied on EAI in BLS ambulances.

Using Big Data to Assess Prescribing Patterns in Greece: The Case of Chronic Obstructive Pulmonary Disease.

INTRODUCTION: Chronic Obstructive Pulmonary Disease (COPD) is one of the top leading causes of death and disability, and its management is focused on reducing risk factors, relieving symptoms, and preventing exacerbations. The study aim was to describe COPD prescribing patterns in Greece by using existing health administrative data for outpatients. METHODS: This is a retrospective cross-sectional study based on prescriptions collected by the largest social insurance fund, during the first and last trimester of 2012. Selection criteria were the prescription of specific active substances and a COPD diagnosis. Extracted information included active substance, strength, pharmaceutical form and number of packages prescribed, diagnosis, time of dispensing, as well as insurees' age, gender, percentage of co-payment and social security unique number. Statistical analysis included descriptive statistics and logistic regression. RESULTS: 174,357 patients received medicines for COPD during the study period. Patients were almost equally distributed between male and female, and age above 55 years was strongly correlated with COPD. Most patients received a long-acting beta agonist plus inhaled corticosteroid combination (LABA +ICS), followed by long-acting muscarinic agonist (LAMA). 63% patients belonging in the 35-54 age received LABA+ICS. LAMA was prescribed more frequently among males and was strongly correlated with COPD. CONCLUSION: The study provides big data analysis of Greek COPD prescribing patterns. It highlights the need for appropriate COPD classification in primary care illustrating the role of electronic prescribing in ensuring appropriate prescribing. Moreover, it indicates possible gender differences in treatment response or disease severity, and the impact of statutory co-payments on prescribing.

Use of ICS/LABA on Asthma Exacerbation Risk in Patients Within a Medical Group.

BACKGROUND: Asthma medication ratio (AMR) ≥ 0.5 has been shown to predict asthma exacerbations. This study explores the impact of increasing or decreasing inhaled corticosteroid/long-acting beta-agonist (ICS/LABA) use over a 7-year period on achieving an AMR of ≥ 0.5. OBJECTIVES: To (a) assess the impact of increasing use of ICS/LABAs on changes in a modified AMR (mAMR) and (b) examine asthma risk over time as measured by an mAMR over a 7-year period, adjusting for differences in baseline characteristics. METHODS: This is a retrospective, observational study using pharmacy and medical claims from a medical group from January 1, 2003, to December 31, 2010. All patients with ≥ 1 asthma diagnosis (ICD-9-CM, 493.xx) with ≥ 1 inhaled asthma medication dispensed in each year of eligibility were included. The mAMR = total ICS controllers dispensed/(total ICS controllers dispensed + albuterol dispensed). The proportion of ICS/LABA use was determined as the number of ICS/LABA canisters dispensed/(total of ICS/LABA + ICS dispensed). Generalized linear mixed models were used to assess the effect of incremental change in ICS/LABA use on mAMR over 7 years, adjusting for differences in resource utilization, time, and asthma medication use.  RESULTS: Nine hundred ninety patients (mean age [± SD] 34.7 years [± 18.2], 61.7% female) met all criteria. Overall, mean mAMR increased over time, while mean albuterol use decreased over time. Adjusting for covariates, we found that a 10% increase in ICS/LABA use was associated with a 9% increase (adjusted OR = 1.09, 95% CI = 1.06-1.12) in the likelihood of achieving an mAMR ≥ 0.5, while a 50% increase in ICS/LABA use was associated with a 53% increase (OR = 1.53, 95% CI = 1.31-1.80) in the likelihood of achieving an mAMR ≥ 0.5. CONCLUSIONS: Increase in ICS/LABA use over time in a population of asthma patients was significantly associated with a higher likelihood of achieving an mAMR ≥ 0.5.

Use of asthma control indicators in measuring inhaled corticosteroid effectiveness in asthmatic smokers: a systematic review.

OBJECTIVE: The objective of this review is to explore how current research measures the effectiveness of inhaled corticosteroids (ICS) in smokers with asthma. DATA SOURCES: PubMed, CINAHL and PsycINFO databases were searched for combinations of terms relating to asthma, tobacco use and ICS effectiveness. STUDY SELECTIONS: The search was limited to articles published between 2004 and 2015, in English language. Studies met inclusion criteria if reporting the use of guideline-based asthma control indicators to measure the therapeutic effects of ICS or ICS combination therapies. This review did not exclude articles based on study design. Data were extracted and summarized to describe how indicators were measured across studies in order to characterize and describe the effects of ICS in smokers. RESULTS: Thirteen studies were included in this review. Six of these 13 studies used only one indicator to measure asthma control in smokers and ICS was found to improve asthma in only one of six of these studies. Of studies evaluating combination therapy, three of four studies reported a therapeutic benefit to smokers. In these studies of combination therapy multiple indicators of control were measured to assess drug effects. CONCLUSIONS: To assess the therapeutic benefit of ICS drugs in smokers, multiple indicators should be measured to determine if current therapy is improving asthma control. Asthma therapy should then be adjusted based on the patient's current asthma status. The development of clinical treatment guidelines for asthmatic smokers may help clinicians make best-practice, evidence-based recommendations in order to optimize care for these patients.

Application of multicategory exposure marginal structural models to investigate the association between long-acting beta-agonists and prescribing of oral corticosteroids for asthma exacerbations in the Clinical Practice Research Datalink.

OBJECTIVE: To examine the comparative effectiveness of inhaled long-acting beta-agonist (LABA), inhaled corticosteroid (ICS), and ICS/LABA combinations. METHODS: We used a retrospective cohort design of patients older than 12 years with asthma diagnosis in the Clinical Practice Research Datalink to evaluate asthma-related morbidity measured by oral corticosteroid (OCS) initiation within 12 months of initiating LABAs, ICSs, or ICSs/LABAs. Asthma severity 12 months before drug initiation (use of OCSs, asthma-related hospital or emergency department visits, and number of short-acting beta-agonist prescriptions) and during follow-up (short-acting beta-agonist prescriptions and total number of asthma drug classes) was adjusted as a time-varying variable via marginal structural models. RESULTS: A total of 51,103 patients with asthma were followed for 12 months after receiving first prescription for study drugs from 1993 to 2010. About 92% initiated ICSs, 1% initiated LABAs, and 7% initiated ICSs/LABAs. Compared with ICSs, LABAs were associated with a 10% increased risk of asthma exacerbations requiring short courses of OCSs (hazard ratio [HR] 1.10; 95% confidence interval [CI] 1.07-1.18). ICS/LABA initiators were 62% less likely than ICS initiators (HR 0.38; 95% CI 0.12-0.66) and 50% less likely than LABA initiators to receive OCS prescriptions for asthma exacerbations (HR 0.50; 95% CI 0.14-0.78). CONCLUSIONS: In concordance with current asthma management guidelines, inhaled LABAs should not be prescribed as monotherapy to patients with asthma. The findings suggest the presence of time-dependent confounding by asthma severity, which was accounted for by the marginal structural model.

Childhood Asthma Hospital Discharge Medication Fills and Risk of Subsequent Readmission.

OBJECTIVE: To assess the relationship between posthospitalization prescription fills for recommended asthma discharge medication classes and subsequent hospital readmission. STUDY DESIGN: This was a retrospective cohort analysis of Medicaid Analytic Extract files from 12 geographically diverse states from 2005-2007. We linked inpatient hospitalization, outpatient, and prescription claims records for children ages 2-18 years with an index hospitalization for asthma to identify those who filled a short-acting beta agonist, oral corticosteroid, or inhaled corticosteroid within 3 days of discharge. We used a multivariable extended Cox model to investigate the association of recommended medication fills and hospital readmission within 90 days. RESULTS: Of 31,658 children hospitalized, 55% filled a beta agonist prescription, 57% an oral steroid, and 37% an inhaled steroid. Readmission occurred for 1.3% of patients by 14 days and 6.3% by 90 days. Adjusting for patient and billing provider factors, beta agonist (hazard ratio [HR] 0.67, 95% CI 0.51, 0.87) and inhaled steroid (HR 0.59, 95% CI 0.42, 0.85) fill were associated with a reduction in readmission at 14 days. Between 15 and 90 days, inhaled steroid fill was associated with decreased readmission (HR 0.87, 95% CI 0.77, 0.98). Patients who filled all 3 medications had the lowest readmission hazard within both intervals. CONCLUSIONS: Filling of beta agonists and inhaled steroids was associated with diminished hazard of early readmission. For inhaled steroids, this effect persisted up to 90 days. Efforts to improve discharge care for asthma should include enhancing recommended discharge medication fill rates.