Opioid use surrounding diagnosis and follow-up in patients with ankylosing spondylitis, psoriatic arthritis, and rheumatoid arthritis: Results from US claims databases.

OBJECTIVE: To describe patients' use of opioids in the year preceding and year following new diagnosis of ankylosing spondylitis (AS), psoriatic arthritis (PsA), or rheumatoid arthritis (RA), compared with patients without the/se diseases. METHODS: This study used US IBM® MarketScan® Commercial Claims and Encounters (CCAE) and Medicaid data and included three cohorts, comprised of incident cases of AS, PsA, or RA (2010-2017). Three matched comparator patients (without the incident disease) were selected for each patient within the disease cohort. Opioid use and appropriate treatment exposure (as defined by US guideline recommendations) in the 12-month baseline and follow-up periods were evaluated using descriptive analyses. RESULTS: Prevalence of claims for opioids was higher for disease cohorts vs. comparators in CCAE; 36.4% of patients with AS, 29.5% with PsA, and 44.4% with RA did not have any claim for guideline-appropriate therapy in follow-up. Prevalence of claims for opioids was also higher for disease cohorts vs. comparators in Medicaid; 30.6% of patients with AS, 36.6% with PsA, and 65.4% with RA did not have any claim for guideline-appropriate therapy in follow-up. CONCLUSIONS: In patients with AS, PsA, or RA, there was high reliance on opioids at and around the time of diagnosis. Significant proportions of patients were not on appropriate treatment as defined by professional society post-diagnosis guidelines; this discordance between actual patient therapies and treatment recommendations may suggest a need for better awareness of appropriate pain management and treatment strategies in rheumatic diseases. Key Points • This study analysed opioid use among patients with ankylosing spondylitis (AS), psoriatic arthritis (PsA), or rheumatoid arthritis (RA), and adds to current knowledge by expanding beyond assessment of opioid use at diagnosis, to the year before and after diagnosis. • Opioid use was found to be highly prevalent in AS, PsA, and RA in the year prior to diagnosis and, interestingly, was still seen during the year after diagnosis. • Opioids are neither disease modifying, nor a targeted/recommended treatment for chronic autoimmune diseases. In addition to their association with significant economic costs, opioids are potentially hazardous and are not better than alternative treatments with superior safety profiles. • The reasons behind opioid prescribing patterns should be explored further to support movement to targeted therapies.

Economic burden of joint analysis in psoriasis: US claims analysis.

OBJECTIVES: Few studies have assessed the economic burden of concomitant joint disease in patients with psoriasis (PSO). This analysis compared health care resource utilization (HCRU) and health care costs in patients with PSO vs those with psoriatic arthritis (PsA). STUDY DESIGN: This was a retrospective database analysis of US commercially insured patients with PSO or PsA. METHODS: Electronic health records (EHRs) and claims in Optum's deidentified Integrated Claims-Clinical data set from 2007 to 2018 were analyzed. Patients were followed up from the first PSO or PsA diagnosis for up to 5 years. Patients with claims or diagnosis codes in EHR data for PSO ("PSO only") were propensity score matched to patients with claims/diagnosis codes for both PSO and PsA ("PSO-PsA"). RESULTS: The matching algorithm generated 4418 matched patient pairs. During follow-up, PSO-PsA patients had greater HCRU than PSO-only patients, including more cumulative all-cause outpatient claims (P ≤ .05 at each year of follow-up). Mean total annual health care costs per patient were higher in PSO-PsA patients than PSO-only patients (PSO only: $14,546-$15,800 vs PSO-PsA: $21,581-$22,868; P < .05 at each year of follow-up). All-cause outpatient and pharmacy costs were also higher in the PSO-PsA cohort (P < .05 at each year of follow-up). CONCLUSIONS: Comorbid joint disease in PSO is associated with greater costs and use of health care resources than PSO alone. These findings underscore the need for dermatologists to be vigilant about detection and treatment of joint symptoms. Early PsA diagnosis and therapy are crucial to improve patient outcomes and reduce the potential economic burden.

The Annual Diagnostic Prevalence of Ankylosing Spondylitis and Axial Spondyloarthritis in the United States Using Medicare and MarketScan Databases.

OBJECTIVE: The objective of this study was to investigate the diagnostic prevalence of ankylosing spondylitis (AS) and axial spondyloarthritis (axSpA) in the United States and examine treatment patterns for these diseases. METHODS: This retrospective observational cohort study drew from 2006-2014 data in the US Medicare Fee-for-Service and IBM MarketScan databases. AS and axSpA diagnoses were identified through International Classification of Diseases, Ninth Revision [ICD-9] codes. Diagnostic prevalence (per 10,000 patients) was calculated as patients with AS and axSpA with full insurance coverage in each calendar year divided by the total patients with full insurance coverage in the same year. Two diagnosis definitions were used: definition 1 (D1), one or more relevant ICD-9 codes from hospital claims or two or more relevant ICD-9 codes from outpatient claims; definition 2 (D2), one or more codes from hospital/outpatient claims. Primary analyses assessed annual AS and axSpA prevalence (D1); sensitivity analyses assessed annual (D2) and 2-year prevalence. Patterns in prevalence and treatment use were analyzed descriptively; no statistical tests were performed. RESULTS: An increase in AS prevalence (per 10,000 patients) was seen from 2006 to 2014 in primary analyses (Medicare: 2.12-3.60; MarketScan: 0.85-1.42) and sensitivity analyses. A similar trend occurred for axSpA (Medicare: 4.39-6.52; MarketScan: 1.33-2.21). For Medicare, the proportion of patients with AS (D1) using tumor necrosis factor α inhibitors (TNFis), conventional synthetic antirheumatic drugs (csARDs), nonsteroidal antiinflammatory drugs (NSAIDs), opioids, and glucocorticoids remained relatively stable; for MarketScan, TNFi-treated patients increased (51.7% to 65.7%) and NSAID-treated patients decreased (63.5% to 55.7%). CONCLUSION: AS and axSpA prevalence may have increased in the United States between 2006 and 2014. Reasons are unknown, but this may be due to increased disease awareness, among other factors.

Occurrence of Possible Rheumatologic Immune-Related Adverse Events (rh-irAEs) Associated with Immune Checkpoint Inhibitor (ICI) Therapy.

INTRODUCTION: Current epidemiologic literature of rheumatologic immune-related adverse events (rh-irAEs) consists of clinical trials, case reports, or smaller, single-center series. We evaluate the occurrence of rh-irAEs during immune checkpoint inhibitor (ICI) therapy from US commercial claims data. METHODS: Patients newly initiating ICI therapy in commercial claims data were eligible for inclusion. Rh-irAEs were defined using ≥ 1 International Classification of Diseases (ICD)-9 or ICD-10-Clinical Modification (CM) claims for selected events, ranging from joint pain and myalgia to ankylosing spondylitis and psoriasis. The percentage of patients experiencing rh-irAEs after ICI initiation was determined. RESULTS: A total of 5722 patients initiating an ICI between January 1, 2012, and June 30, 2018, were included; 201 patients (3.5%) had a history of rheumatic disease. Among the 5521 patients without a history of rheumatic disease, 29.6% experienced ≥ 1 rh-irAE in follow-up, decreasing to 22.6% when assessing events for which there was no diagnostic history. Limiting to claims for rh-irAE with a rheumatologist provider, the proportion of patients experiencing an event decreased to 0.9%. Among patients with a history of rheumatic disease, 71.6% experienced ≥ 1 rh-irAE. Limiting to events for which the patient did not have a history during baseline, 35.3% experienced an event. CONCLUSIONS: Occurrence of rh-irAEs during ICI use is higher in patients with pre-existing rheumatic disease compared to those with no pre-existing rheumatic disease. However, the most common events were not definitive rheumatic diseases but rather symptoms, such as pain in joints. Occurrence of events associated with a rheumatologist provider was substantially lower, suggesting that either patients are not referred to a rheumatologist or referral does not result in confirmation of the diagnosis by the rheumatologist.

Clinical Burden of Concomitant Joint Disease in Psoriasis: A US-Linked Claims and Electronic Health Records Database Analysis.

BACKGROUND: Few studies have evaluated the clinical burden of concomitant joint disease in patients with psoriasis (PSO). The objective of this study was to assess comorbidity rates in patients with psoriatic arthritis (PsA) compared with PSO alone. METHODS: This was a retrospective study of US patients with prevalent PSO. Linked medical claims and electronic health records (EHR) in Optum's de-identified Integrated Claims-Clinical dataset were analyzed from 2007 to 2018. Patients were followed for up to 5 years after the first claim/diagnostic code for PSO (index date). Baseline comorbidity prevalence and follow-up rates (cases per 1000 person-years) were assessed using descriptive statistics. Comorbidity rate analysis included patients with the respective comorbidity at baseline. RESULTS: Baseline demographics and comorbidity prevalence were numerically similar between patients with concomitant joint disease (PSO-PsA) and those with PSO alone (PSO-only). During follow-up, comorbidity rates were higher in patients in the PSO-PsA group than patients in the PSO-only group. Ratios of PSO-PsA comorbidity rates relative to PSO-only ranged from 1.1 for allergies and infections to 1.7 for fatigue, diabetes, and obesity. Comorbidity rate ratios increased from year 1 to year 5 for hypertension (1.05-1.34), hyperlipidemia (0.94-1.13), diabetes (1.00-1.49), cardiovascular disease (1.03-1.66), depression (0.97-1.19), and anxiety (0.87-0.98). CONCLUSIONS: Patients with PsA have a larger clinical burden, characterized by higher comorbidity rates, than those with PSO. Future research should explore PsA risk factors and how physicians can monitor and treat patients with PSO to reduce the risk of PsA and the associated clinical burden.

Psoriasis is a disease that causes scaly, red skin patches that are itchy or painful. About one-third of people who have psoriasis also develop joint pain. This combination of skin symptoms and joint disease is known as psoriatic arthritis. Having psoriatic arthritis can have a greater effect on people's quality of life than having psoriasis alone. People with psoriasis or psoriatic arthritis often have other medical conditions that are not related to their skin or joints. We know that some conditions, such as obesity and high blood pressure, are more common in people with psoriatic arthritis than in those who only have psoriasis. However, more evidence is needed to understand if this pattern is also seen with other medical conditions. We used a large database of medical insurance claims and electronic health records to see what other medical conditions people with psoriatic arthritis or psoriasis had. We found that people with psoriatic arthritis were more likely to have other medical conditions than those with only psoriasis, including high blood pressure, obesity, diabetes, heart disease, and mental health conditions. These differences became larger over the years covered by this study (2007­2018). The results of this study show that people with psoriatic arthritis are more likely to have additional medical conditions than those who have psoriasis alone. Therefore, it is very important that doctors understand how to reduce the risk of joint disease in their patients with psoriasis.

Epidemiology and Treatment of Patients with Rheumatoid Arthritis, Psoriatic Arthritis and Psoriasis in Germany: A Real-World Evidence Study.

INTRODUCTION: Rheumatoid arthritis (RA), psoriatic arthritis (PsA) and psoriasis (PSO) are chronic inflammatory diseases that have a substantial impact on patients' health. This retrospective database study aimed to assess the epidemiology, comorbidities, diagnosis and treatment patterns of RA, PsA and PSO in the German population. METHODS: Data were extracted from the Deutsche Forschungsdatenbank für Abrechnungsinformationen der Krankenversicherung database from 2012 to 2016 for patients aged ≥ 18 years holding full health coverage in the reporting year at least. Diagnoses were defined according to International Classification of Diseases (ICD)-10 codes. Reported outcomes included prevalence and incidence rates, pre-defined comorbidities, diagnosing and treating physicians, and treatment exposure. A subgroup analysis was performed for women of childbearing age (females aged 18-45 years). RESULTS: The prevalence rates of RA, PsA and PSO in Germany were consistent over the study period; by 2016 they were 0.4%, 0.3% and 2.1%, respectively, and in women of childbearing age they were 0.2%, 0.2% and 1.5%, respectively. RA, PsA and PSO were predominantly observed among patients aged > 45 years. RA and PsA were more prevalent in women, while PSO had an approximately equal gender distribution. Depressive episodes were the most frequently reported comorbidity in 2016 (RA: 25.7%; PsA: 25.1%; PSO: 17.8%), and this was similar in women of childbearing age (RA: 20.5%; PsA: 23.4%; PSO: 16.3%). Approximately 50% of patients with RA and PsA and 6% of patients with PSO were receiving systemic treatment in 2016, of which methotrexate (RA: 38.4%; PsA: 30.2%; PSO: 2.2%) was most common. Biologic therapies were the least frequently used treatment options (RA: 28.9%; PsA: 20.9%; PSO: 1.8%). CONCLUSIONS: This analysis provides key epidemiological information for patients with RA, PsA and PSO, including in women of childbearing age, in Germany and highlights common comorbidities and that patients were likely receiving insufficient treatment for these diagnoses.

Incidence, risk factors and re-exacerbation rate of severe asthma exacerbations in a multinational, multidatabase pediatric cohort study.

BACKGROUND: There are sparse real-world data on severe asthma exacerbations (SAE) in children. This multinational cohort study assessed the incidence of and risk factors for SAE and the incidence of asthma-related rehospitalization in children with asthma. METHODS: Asthma patients 5-17 years old with ≥1 year of follow-up were identified in six European electronic databases from the Netherlands, Italy, the UK, Denmark and Spain in 2008-2013. Asthma was defined as ≥1 asthma-specific disease code within 3 months of prescriptions/dispensing of asthma medication. Severe asthma was defined as high-dosed inhaled corticosteroids plus a second controller. SAE was defined by systemic corticosteroids, emergency department visit and/or hospitalization all for reason of asthma. Risk factors for SAE were estimated by Poisson regression analyses. RESULTS: The cohort consisted of 212 060 paediatric asthma patients contributing to 678 625 patient-years (PY). SAE rates ranged between 17 and 198/1000 PY and were higher in severe asthma and highest in severe asthma patients with a history of exacerbations. Prior SAE (incidence rate ratio 3-45) and younger age increased the SAE risk in all countries, whereas obesity, atopy and GERD were a risk factor in some but not all countries. Rehospitalization rates were up to 79% within 1 year. CONCLUSIONS: In a real-world setting, SAE rates were highest in children with severe asthma with a history of exacerbations. Many severe asthma patients were rehospitalized within 1 year. Asthma management focusing on prevention of SAE is important to reduce the burden of asthma.

Multinational cohort study of mortality in patients with asthma and severe asthma.

BACKGROUND: Data on the risk of death following an asthma exacerbation are scarce. With this multinational cohort study, we assessed all-cause mortality rates, mortality rates following an exacerbation, and patient characteristics associated with all-cause mortality in asthma. METHODS: Asthma patients aged ≥18 years and with ≥1 year of follow-up were identified in 5 European electronic databases from the Netherlands, Italy, UK, Denmark and Spain during the study period January 1, 2008-December 31, 2013. Patients with asthma-COPD overlap were excluded. Severe asthma was defined as use of high dose ICS + use of a second controller. Severe asthma exacerbations were defined as emergency department visits, hospitalizations or systemic corticosteroid use, all for reason of asthma. RESULTS: The cohort consisted of 586,436 asthma patients of which 42,611 patients (7.3%) had severe asthma. The age and sex standardized all-cause mortality rates ranged between databases from 5.2 to 9.5/1000 person-years (PY) in asthma, and between 11.3 and 14.8/1000 PY in severe asthma. The all-cause mortality rate in the first week following a severe asthma exacerbation ranged between 14.1 and 59.9/1000 PY. Mortality rates remained high in the first month following a severe asthma exacerbation and decreased thereafter. Higher age, male gender, comorbidity, smoking, and previous severe asthma exacerbations were associated with mortality. CONCLUSION: All-cause mortality following a severe exacerbation is high, especially in the first month following the event. Smoking cessation, comorbidity-management and asthma-treatment focusing on the prevention of exacerbations might reduce associated mortality.

Opioid Use in Patients with Ankylosing Spondylitis Is Common in the United States: Outcomes of a Retrospective Cohort Study.

OBJECTIVE: To assess the prevalence of chronic opioid use in patients with ankylosing spondylitis (AS), and to compare the characteristics of patients with and without chronic opioid use. METHODS: This was a retrospective cohort study of patients with AS identified in the Truven Health MarketScan Research database between January 1, 2012, and March 31, 2017. Commercial and Medicaid claims data were examined using both specific (720.0 and M45.x) and broader (720.x and M45.x) International Classification of Diseases (ICD) coding definitions. Patients were aged ≥ 18 years on the date of first qualifying ICD code occurrence (the index date). Demographics and clinical characteristics were assessed in the 12-month period preceding the index date. The 12-month followup period was used to assess prevalence and characteristics of chronic opioid use. RESULTS: Chronic opioid use was common among patients with commercial claims (23.5% of ICD 720.0 patients; 27.3% of ICD 720.x patients), and especially those with Medicaid claims (57.1% and 76.7%, respectively). The proportion of patients with claims for anti-tumor necrosis factor therapies during followup was often low, and for Medicaid patients was lower among those with chronic opioid use (29.6% of ICD 720.0 patients; 2.3% of ICD 720.x patients) than those without (47.1% and 7.1%, respectively). Among chronic opioid users in all cohorts, the cumulative supply of opioids was typically high (≥ 270 days in the followup period); most opioids prescribed were Schedule II. CONCLUSION: Patients with AS receive opioids with disturbing frequency. The infrequent prescription of recommended therapies to these patients reflects a need to optimize treatment further through education of patients and healthcare professionals alike.

Demographic and Clinical Characteristics of COPD Patients at Different Blood Eosinophil Levels in the UK Clinical Practice Research Datalink.

Blood eosinophil count may be a useful biomarker for predicting response to inhaled corticosteroids and exacerbation risk in chronic obstructive pulmonary disease (COPD) patients. The optimal cut point for categorizing blood eosinophil counts in these contexts remains unclear. We aimed to determine the distribution of blood eosinophil count in COPD patients and matched non-COPD controls, and to describe demographic and clinical characteristics at different cut points. We identified COPD patients within the UK Clinical Practice Research Database aged ≥40 years with a FEV1/FVC <0.7, and ≥1 blood eosinophil count recorded during stable disease between January 1, 2010 and December 31, 2012. COPD patients were matched on age, sex, and smoking status to non-COPD controls. Using all blood eosinophil counts recorded during a 12-month period, COPD patients were categorized as "always above," "fluctuating above and below," and "never above" cut points of 100, 150, and 300 cells/µL. The geometric mean blood eosinophil count was statistically significantly higher in COPD patients versus matched controls (196.6 cells/µL vs. 182.1 cells/µL; mean difference 8%, 95% CI: 6.8, 9.2), and in COPD patients with versus without a history of asthma (205.0 cells/µL vs. 192.2 cells/µL; mean difference 6.7%, 95%, CI: 4.9, 8.5). About half of COPD patients had all blood eosinophil counts above 150 cells/µL; this persistent higher eosinophil phenotype was associated with being male, higher body mass index, and history of asthma. In conclusion, COPD patients demonstrated higher blood eosinophil count than non-COPD controls, although there was substantial overlap in the distributions. COPD patients with a history of asthma had significantly higher blood eosinophil count versus those without.

One-year risk of serious infection in patients treated with certolizumab pegol as compared with other TNF inhibitors in a real-world setting: data from a national U.S. rheumatoid arthritis registry.

BACKGROUND: Registry studies provide a valuable source of comparative safety data for tumor necrosis factor inhibitors (TNFi) used in rheumatoid arthritis (RA), but they are subject to channeling bias. Comparing safety outcomes without accounting for channeling bias can lead to inaccurate comparisons between TNFi prescribed at different stages of the disease. In the present study, we examined the incidence of serious infection and other adverse events during certolizumab pegol (CZP) use vs other TNFi in a U.S. RA cohort before and after using a methodological approach to minimize channeling bias. METHODS: Patients with RA enrolled in the Corrona registry, aged ≥ 18 years, initiating CZP or other TNFi (etanercept, adalimumab, golimumab, or infliximab) after May 1, 2009 (n = 6215 initiations), were followed for ≤ 12 months. A propensity score (PS) model was used to control for baseline characteristics associated with the probability of receiving CZP vs other TNFi. Incidence rate ratios (IRRs) of serious infectious events (SIEs), malignancies, and cardiovascular events (CVEs) in the CZP group vs other TNFi group were calculated with 95% CIs, before and after PS matching. RESULTS: Patients were more likely to initiate CZP later in the course of therapy than those initiating other TNFi. CZP initiators (n = 975) were older and had longer disease duration, more active disease, and greater disability than other TNFi initiators (n = 5240). After PS matching, there were no clinically important differences between CZP (n = 952) and other TNFi (n = 952). Before PS matching, CZP was associated with a greater incidence of SIEs (IRR 1.53 [95% CI 1.13, 2.05]). The risk of SIEs was not different between groups after PS matching (IRR 1.26 [95% CI 0.84, 1.90]). The 95% CI of the IRRs for malignancies or CVEs included unity, regardless of PS matching, suggesting no difference in risk between CZP and other TNFi. CONCLUSIONS: After using PS matching to minimize channeling bias and compare patients with a similar likelihood of receiving CZP or other TNFi, the 1-year risk of SIEs, malignancies, and CVEs was not distinguishable between the two groups.

The impact of long-term systemic glucocorticoid use in severe asthma: A UK retrospective cohort analysis.

OBJECTIVE: Systemic glucocorticoids (SGCs) are a treatment option for severe asthma but are associated with the development of adverse events (AEs). Evidence on the extent of SGC use and the relationship between SGC dose and AE risk in severe asthma is limited. METHODS: Patients with severe asthma (Global Initiative for Asthma step 4/5), with no SGC use during the <6-12 months before severe asthma determination (index date) were identified in the UK-based Clinical Practice Research Datalink database (2004-2012). Patients were assessed for SGC exposure and an incident diagnosis of an SGC-related AE (cataracts, diabetes, myocardial infarction [MI], osteoporosis, peptic ulcer or stroke) during the 8-year observation phase. The dose-related risk of an SGC-related AE was determined using AE-specific Cox proportional hazards models. RESULTS: Overall, 75% of 60,418 patients identified with severe asthma received SGC during the 8-year follow-up, with the majority receiving an average of >0-≤2.5 mg/day. The risk of diabetes (hazard ratio [HR]:1.20 [95% confidence interval (CI): 1.11, 1.30]), MI (HR: 1.25 [95% CI: 1.09, 1.43]) and osteoporosis (HR: 1.64 [95% CI: 1.51, 1.78]) was increased at low SGC doses (0-2.5 mg/day), with further risk increases at doses >2.5 mg/day versus no SGC use. Compared with no SGC use, SGC increased the risk of peptic ulcer in a non-dose-dependent manner, but the risk of stroke was unchanged. CONCLUSIONS: Most patients with severe asthma are exposed to SGC, which increases SGC-related AE risk. This suggests that SGC exposure should be minimized as recommended by asthma treatment guidelines.

Biologic treatment eligibility for real-world patients with severe asthma: The IDEAL study.

OBJECTIVES: Severe asthma comprises several distinct phenotypes. Consequently, patients with severe asthma can be eligible for more than one biologic treatment targeting Th2 inflammation, such as anti-interleukin (IL)-5 and anti-immunoglobulin (Ig) E. The objective of this study was to describe treatment eligibility and overlap in treatment eligibility for mepolizumab (anti-IL-5), omalizumab (anti-IgE) and reslizumab (anti-IL-5) in patients with severe asthma, who were recruited from clinical practice. METHODS: This cross-sectional, single-visit, observational study in six countries enrolled patients with severe asthma (defined by American Thoracic Society/European Respiratory Society guidelines). Assessable patients were analysed as a total cohort and a sub-cohort, who were not currently receiving omalizumab. Treatment eligibility was defined according to the local prescribing information or protocol-defined inclusion/exclusion criteria. Patients currently receiving omalizumab were automatically categorised as omalizumab-eligible. RESULTS: The total cohort comprised 670 patients who met the analysis criteria, of whom 20% were eligible for mepolizumab, 31-41% were eligible for omalizumab (depending on eligibility criteria used), and 5% were eligible for reslizumab. In patients not currently receiving omalizumab (n = 502), proportions eligible for each biologic were similar (mepolizumab: 20%, reslizumab 6%) or lower (omalizumab 7-21%) than those for the total cohort. Overlap in treatment eligibility varied; in mepolizumab-eligible patients not currently receiving omalizumab (n = 101), 27-37% were omalizumab-eligible and 18% were reslizumab-eligible. CONCLUSIONS: Treatment eligibility for mepolizumab and omalizumab was higher than that for reslizumab. Although there was some overlap in treatment eligibility, the patient groups eligible for treatment with anti-IL-5 or anti-IgE therapies were often distinct, emphasising the different phenotypes and endotypes in severe asthma.

Stability of Blood Eosinophil Count in Patients with COPD in the UK Clinical Practice Research Datalink.

Blood eosinophil counts may be predictive of corticosteroid response in chronic obstructive pulmonary disease (COPD) patients. However, little is known about measurement stability, which is important for understanding the utility of blood eosinophil counts as a potential biomarker. We evaluated the stability of blood eosinophil counts over 1 year in a population-based cohort of patients with COPD in primary care. Patients were aged ≥ 40 years with forced expiratory volume in 1 second/forced vital capacity < 0.7 and ≥ 1 blood eosinophil measurement taken during a period of stable disease within 6 months of a COPD diagnosis code recorded between January 1, 2010 and December 31, 2012. Generalized linear mixed models were fitted to log-transformed data to estimate the between-(s2between) and within-patient (s2within) variance in eosinophil count; an intra-class correlation coefficient Ri was calculated (s2between/[s2between + s2within]). A sensitivity analysis was performed from which patients who were prescribed systemic corticosteroids or antibiotics at any time during follow-up were excluded. All models were adjusted for age, gender, smoking status, and asthma history. Overall, 27,557 patients were included in the full cohort (51.5% male, mean age [standard deviation] 71.1 [10.6] years) and 54% of patients had ≥ 2 eosinophil measurements (median 2 [interquartile range 1]) during follow-up. For the full cohort, Ri = 0.64, and in the sensitivity analysis subgroup, Ri = 0.70, mainly due to a decrease in s2within. For patients with COPD in primary care, eosinophil measurements demonstrated reasonable repeatability over 1 year, which increased after exclusion of patients who were prescribed systemic corticosteroids or antibiotics.

The frequency of asthma exacerbations and healthcare utilization in patients with asthma from the UK and USA.

BACKGROUND: Asthma exacerbations are frequent in patients with severe disease. This report describes results from two retrospective cohort studies describing exacerbation frequency and risk, emergency department (ED)/hospital re-admissions, and asthma-related costs by asthma severity in the US and UK. METHODS: Patients with asthma in the US-based Clinformatics™ DataMart Multiplan IMPACT (2010-2011; WEUSKOP7048) and the UK-based Clinical Practice Research Datalink (2009-2011; WEUSKOP7092) databases were categorized by disease severity (Global Initiative for Asthma [GINA]; Step and exacerbation history) during the 12 months pre-asthma medical code (index date). Outcomes included: frequency of exacerbations (asthma-related ED visit, hospitalization, or oral corticosteroid use with an asthma medical code recorded within ±2 weeks) 12 months post-index, asthma-related ED visits/hospitalization, and asthma-related costs 30 days post-index. Risk of a subsequent exacerbation was determined by proportional hazard model. RESULTS: Of the 222,817 and 211,807 patients with asthma included from the US and UK databases, respectively, 12.5 and 8.4% experienced ≥1 exacerbation during the follow-up period. Exacerbation frequency increased with disease severity. Among the 5,167 and 2,904 patients with an asthma-related ED visit/hospitalization in the US and UK databases, respectively, 9.2 and 4.7% had asthma-related re-admissions within 30 days. Asthma-related re-admission rates and costs increased with disease severity, approximately doubling between GINA Step 1 and 5 and in patients with ≥2 versus <2 exacerbations in the previous year. Risk of a subsequent exacerbation increased 32-35% for an exacerbation requiring ED visit/hospitalization versus oral corticosteroids. CONCLUSION: Increased disease severity was associated with higher exacerbation frequency, ED/hospitalization re-admission, costs and risk of subsequent exacerbation, indicating that these patients require high-intensity post-exacerbation management.

Blood Eosinophil Count and Outcomes in Severe Uncontrolled Asthma: A Prospective Study.

BACKGROUND: Severe uncontrolled asthma (SUA) is associated with increased asthma exacerbations. Whether high blood eosinophil counts are related to this burden is uncertain. OBJECTIVES: To determine the relationship of blood eosinophil counts to asthma exacerbations, utilization, and cost in patients with SUA. METHODS: Patients with persistent asthma (age ≥ 12 years) were identified administratively with SUA in phase I by evidencing (1) 2 or more asthma exacerbations; (2) 6 or more medium- or high-dose dispensed canisters of inhaled corticosteroid (ICS) as monotherapy or with long-acting ß2-agonist; and (3) 3 or more dispensed non-ICS controllers. Of the 541 patients with SUA invited to participate in the prospective phase II follow-up study, 261 (48.2%) had blood tests (index date) to determine eosinophil count and other atopic biomarkers. The relationship of blood eosinophil cutoff points to asthma exacerbations and direct costs 1 year after the index date were determined by multivariable regression. RESULTS: A blood eosinophil cutoff point of greater than or equal to 400 cells/mm3 compared with less than 400 cells/mm3, but not 150 cells/mm3 or 300 cells/mm3, was a risk factor in the outcome year in adjusted analyses for 2 or more asthma exacerbations (risk ratio, 1.55; 95% CI, 1.02-2.35; P =.04) and any asthma emergency department visit or hospitalization (risk ratio, 2.29; 95% CI, 1.16-4.55; P =.02), but not for rate of asthma exacerbations or incremental total direct asthma costs per patient ($202; 95% CI, -286 to 691). CONCLUSIONS: A high blood eosinophil count was an independent risk factor for 2 or more asthma exacerbations or any asthma emergency department visit or hospitalization, but not direct costs in patients with SUA, possibly constrained by limited power.

Retrospective cohort analysis of healthcare claims in the United States characterising asthma exacerbations in paediatric patients.

BACKGROUND: Asthma is the most common chronic disease in childhood and places a significant burden on public and private health systems. This retrospective cohort analysis utilised administrative healthcare claims data (US Clinformatics™ Multiplan database; compliant with the US Department of Health & Human Services Health Insurance Portability and Accountability Act) to characterise asthma exacerbations requiring intervention in a US paediatric patient population. METHODS: Patients aged > 1-17 years with a recorded asthma diagnosis and receiving treatment were identified in the US Clinformatics™ Multiplan database over a 9-year period (2004-2012). Both incident and prevalent cases of asthma were included, with the most recently recorded asthma diagnosis designated as the index date. The 12-month period following the index date was analysed for asthma exacerbations, defined as an event requiring treatment with systemic corticosteroid or resulting in an asthma-related hospitalisation or emergency department visit. RESULTS: Data from 734,114 children with asthma (41.5 % females, 58.5 % males) were analysed, of this cohort 34.4 % experienced ≥ 1 exacerbation during the follow-up period. The proportion who experienced ≥ 1 exacerbation increased from 28.9 % in 2004 to 36.3 % in 2012, based on the reported index date. Their mean annual exacerbation frequency was 1.4; 85.8 % of exacerbations were defined by systemic corticosteroids use. A consistent trend of increased exacerbation incidence in the fall and early winter was observed, in particular exacerbations defined by systemic corticosteroid use. A greater proportion of asthma-related hospitalisations were associated with younger age. CONCLUSIONS: Approximately one-third of children experienced ≥ 1 exacerbation in real-world clinical practice. A targeted treatment approach with a focus on those with a history of recurrent exacerbations is recommended to improve asthma control. This targeted approach could also minimise the frequent systemic corticosteroid exposure particularly at an early age when side effects of systemic corticosteroids are more pronounced.

Utilization and Costs of Severe Uncontrolled Asthma in a Managed-Care Setting.

BACKGROUND: Clinical and economic burden of patients with severe uncontrolled asthma (SUA) in a real-world managed-care setting required further documentation. OBJECTIVE: The objective of this study was to determine the characteristics, clinical, and economic burden of SUA in a managed-care setting. METHODS: This observational study identified patients with persistent asthma aged 12 years or more (N = 25,935) using the International Classification of Diseases, 9th Revision asthma codes and Healthcare Effectiveness Data and Information Set administrative criteria. An SUA subgroup was identified when all of the following 3 criteria were met in 2012: (1) 2 or more asthma exacerbations; (2) 6 or more medium- or high-dose dispensed canisters of inhaled corticosteroid (ICS) as monotherapy or with long-acting ß2-agonist; and (3) 3 or more dispensed non-ICS controllers. Health care utilization and direct costs (all-cause and asthma-related) in 2013 were compared between SUA and non-SUA subgroups using multivariable regression. RESULTS: Compared with the non-SUA subgroup (N = 25,350, 97.7%), the SUA subgroup (N = 585, 2.3%) at baseline was significantly older and had more comorbidities, asthma specialist care, controller medication dispensed, and asthma exacerbations. During follow-up, patients with SUA exhibited significantly more asthma exacerbations and short-acting ß2-agonist use, and higher all-cause and asthma-related costs than patients with non-SUA. The adjusted asthma-related average direct cost per patient at follow-up was significantly higher for SUA (mean ± SE) ($2325 ± $75) than non-SUA ($1261 ± $9) with an incremental cost of $1056 (95% CI, $907-$1205). Asthma drugs accounted for the major difference (incremental cost of $848/patient; 95% CI, $737-$959). CONCLUSION: Increases and disparities in health care utilization and direct cost by SUA status suggest that patients with SUA require more intensive therapy, greater attention to adherence and comorbidities, more specialist care, and, possibly, personalized treatment approaches including novel biologic treatments.

Cluster analysis and characterization of response to mepolizumab. A step closer to personalized medicine for patients with severe asthma.

RATIONALE: Detailed characterization of asthma phenotypes is essential for identification of responder populations to allow directed personalized medical intervention. OBJECTIVES: The aim of this study was to identify distinctive patient characteristics within subgroups of a well-characterized severe asthma population at risk for exacerbations and to determine the treatment response within each subgroup. METHODS: A supervised cluster analysis with recursive partitioning approach was applied to data from the Dose Ranging Efficacy And safety with Mepolizumab (DREAM) study to identify characteristics that maximized the differences across subgroups. Exacerbation rate ratios were calculated for each cluster comparing mepolizumab versus placebo. MEASUREMENTS AND MAIN RESULTS: Three predictors were identified in four primary clusters: blood eosinophils, airway reversibility, and body mass index. The reduction in exacerbations was significantly greater in patients who received mepolizumab (clusters 2, 3, and 4) with raised eosinophils (responder population). Cluster 2 with low airway reversibility (mean, 11%) had a 53% reduction in exacerbations. These patients more frequently reported sinusitis and nasal polyposis. Those with higher airway reversibility (mean, 28%) were further split by body mass index. The nonobese versus obese (clusters 3 and 4) had a 35 and 67% reduction in exacerbations, respectively. Cluster 4 also had patients with more comorbidities, including hypertension, weight gain, and anxiety. CONCLUSIONS: Using supervised cluster analysis helped identify specific patient characteristics related to disease and therapeutic response. Patients with eosinophilic inflammation received significant therapeutic benefit with mepolizumab, and responses differed within clusters. Clinical trial registered with www.clinicaltrials.gov (NCT01000506).