Benralizumab in severe eosinophilic asthma by previous biologic use and key clinical subgroups: real-world XALOC-1 programme.

BACKGROUND: Pivotal Phase 3 trials and real-world studies have demonstrated benralizumab's overall efficacy and safety in severe eosinophilic asthma (SEA). Additional large-cohort data are needed to confirm its real-world effectiveness in SEA according to previous biologic use and key baseline characteristics important for treatment selection. METHODS: XALOC-1 is a large, multinational, retrospective, observational, real-world study programme of benralizumab in adults with SEA. This 48-week integrated analysis assessed annualised exacerbation rate (AER), maintenance oral corticosteroid (mOCS) use, asthma symptom control and lung function during a 12-month baseline period and up to 48 weeks after benralizumab initiation. Subgroup analyses were based on previous biologic use and key baseline clinical characteristics (mOCS use, blood eosinophil count, exacerbation history, age at asthma diagnosis, fractional exhaled nitric oxide level and presence of atopy and chronic rhinosinusitis with nasal polyps). RESULTS: Of 1002 patients analysed, 380 were biologic-experienced. At Week 48, 71.3% were exacerbation-free (versus 17.2% at baseline); relative reduction in AER was 82.7% overall and 72.9% in biologic-experienced patients; rates were maintained across all key clinical characteristic subgroups. Of patients using mOCS at baseline (n=274), 47.4% (130/274) eliminated their use by Week 48; the mean reduction from baseline in daily dose was 51.2% and, notably, 34.9% in biologic-experienced patients (n=115). Clinically significant improvements in asthma symptom control and lung function were observed. CONCLUSION: In this large, real-world programme, SEA patients treated with benralizumab had substantial improvements in clinical outcomes irrespective of previous biologic use and key clinical characteristics important to therapeutic decision-making in clinical practice.

Achieving clinical outcomes with benralizumab in severe eosinophilic asthma patients in a real-world setting: orbe II study.

BACKGROUND: The ORBE II study aimed to describe the characteristics and clinical outcomes of adult patients with severe eosinophilic asthma (SEA) treated with benralizumab in a real-world setting in Spain. METHODS: ORBE II (NCT04648839) was an observational, retrospective cohort study in adult SEA patients who had been prescribed benralizumab. Demographic and clinical data of 204 SEA patients were collected 12 months prior to benralizumab initiation (baseline) and at follow-up. Exacerbation rate, asthma symptoms, maintenance oral corticosteroid (OCS) use and lung function were evaluated, among other variables. RESULTS: A total of 204 SEA patients were evaluated. Mean (standard deviation, SD) age of the study population was 56.4 (12.4) years, 62.3% were women and mean (SD) duration of asthma was 15.1 (12.7) years. Median (Q1-Q3) follow-up duration was 19.5 (14.2-24.2) months. At baseline, 72.6% of the overall population (OP) presented blood eosinophil counts ≥ 300 cells/µL; 36.8% had comorbid chronic rhinosinusitis with nasal polyps (CRSwNP); 84.8% reported at least one severe exacerbation, and 29.1% were OCS-dependent. At 1 year of follow-up, patients receiving benralizumab treatment had a 85.6% mean reduction in exacerbations from baseline, and 81.4% of patients achieved zero exacerbations. We also found a clinically relevant mean (SD) increase in pre-bronchodilator (BD) FEV1 of 331 (413) mL, with 66.7% of patients achieving a pre-BD FEV1 increase ≥ 100 mL, and 46.3% of patients achieving a pre-BD FEV1 ≥ 80% of predicted. Regarding symptom control, 73.8% of the OP obtained an ACT score ≥ 20 points. After 1 year of follow-up, mean reduction in the daily OCS dose was 70.5%, and complete OCS withdrawal was achieved by 52.8% of the OCS-dependent patients. Almost half (43.7%) of the OP on benralizumab met all four criteria for clinical remission. Patients with concomitant CRSwNP obtained similar or enhanced outcomes. CONCLUSIONS: These data support the real-world benefits of benralizumab in SEA patients, and particularly in those with concomitant CRSwNP. TRIAL REGISTRATION: NCT04648839.

Impact of COPD Exacerbations and Burden of Disease in Spain: AVOIDEX Study.

Purpose: Chronic obstructive pulmonary disease (COPD) is characterized by high morbidity and mortality, with a considerable consumption of healthcare resources (HRU). This study aims to obtain real world evidence regarding the consequences of COPD exacerbations and to provide updated data on the burden of this disease and its treatment. Patients and Methods: A retrospective study in seven Spanish regions was conducted among COPD patients diagnosed between 1/01/2010 and 31/12/2017. The index date was the diagnosis of COPD and patients were followed until lost to follow-up, death or end of the study, whichever occurred first. Patients were classified by patient pattern (incident or prevalent), type and severity of exacerbations, and treatments prescribed. Demographic and clinical characteristics were evaluated, together with the incidence of exacerbations, comorbidities, and the use of HRU, during the baseline (12 months before the index date) and the follow-up periods by incident/prevalent and treatment prescribed. Mortality rate was also measured. Results: The study included 34,557 patients with a mean age of 70 years (standard deviation: 12). The most frequent comorbidities were diabetes, osteoporosis, and anxiety. Most patients received inhaled corticosteroids (ICS) with long-acting beta agonists (LABA), or long-acting muscarinic agonists (LAMA), followed by LABA with LAMA. Incident patients (N=8229; 23.8%) had fewer exacerbations than prevalent patients (N=26328; 76.2%), 0.3 vs 1.2 exacerbations per 100 patient-years. All treatment patterns present a substantial disease burden, which seems to increase with the evolution of the disease (ie moving from initial treatments to combination therapies). The overall mortality rate was 40.2 deaths/1000 patient-years. General practitioner visits and tests were the HRU most frequently required. The frequency and severity of exacerbations positively correlated with the use of HRU. Conclusion: Despite receiving treatment, patients with COPD suffer a considerable burden mainly due to exacerbations and comorbidities, which require a substantial use of HRU.

Effect of Stepping Up to High-Dose Inhaled Corticosteroids in Patients With Asthma: UK Database Study.

BACKGROUND: It is unclear whether patients with asthma benefit from stepping up to high-dose inhaled corticosteroids (ICSs). OBJECTIVE: To determine the effectiveness of stepping up to high-dose ICSs. METHODS: A historic cohort study of patients with asthma (≥13 years old), identified from 2 large UK electronic medical record databases, was conducted. Patients who remained on medium-dose ICSs were compared with those who stepped up from medium- to high-dose ICSs, whereas patients who stepped up from low- to medium-dose ICSs were compared with those who stepped up from low- to high-dose ICSs. Time to first severe exacerbation (primary outcome) between treatment groups was compared using multivariable Cox proportional hazards models, and the number of exacerbations and antibiotics courses was analyzed using negative binomial regression. Inverse probability of treatment weighting was used to handle confounding. RESULTS: The mean follow-up time to first exacerbation was 2.7 ± 2.7 years for those who remained on stable medium-dose ICSs and 2.0 ± 2.2 years for those who stepped up from medium- to high-dose ICSs. A similar pattern was noted for those who stepped up from low- to medium-dose ICSs (2.6 ± 2.5 years) and from low- to high-dose ICSs (2.3 ± 2.5 years). Patients who stepped up from medium- to high-dose ICSs (n = 6879) had a higher risk of exacerbations during follow-up compared with those who remained on medium-dose ICSs (n = 51,737; hazard ratio, 1.17; 95% CI, 1.12-1.22). This was similar in patients stepping up from low- to high-dose (n = 3232) compared with low- to medium-dose (n = 12,659) ICSs (hazard ratio, 1.10; 95% CI, 1.04-1.17). A step-up to high-dose ICSs was also associated with a higher number of asthma exacerbations and antibiotics courses. No significant difference in associations was found across subgroups of patients with different blood eosinophil counts. CONCLUSIONS: We found no evidence that a step-up to high-dose ICSs is effective in preventing future asthma exacerbations.

Clinical burden related to oral corticosteroid treatment of severe asthma in Spain: LEVANTE study.

BACKGROUND: Severe asthma treatment with oral corticosteroids (OCS) added to inhaled corticosteroids and a long-acting ß2-agonist (ICS-LABA) may result in more treatment burden and increased adverse effects. OBJECTIVE AND METHODS: This ambispective multicenter observational study aimed at describing the clinical burden in patients with severe asthma on stable high-dose ICS-LABA who received OCS during ≥6 months (maintenance group) or ≥2 cycles in the previous 12 months (bursts group). Data collection comprised a retrospective 12-month baseline period and 2 follow-up visits at 3 and 6 months. RESULTS: Eighty-nine patients were evaluable (30 on maintenance, 59 on bursts). At baseline, mean (SD) daily prednisone equivalent exposure in the total population was 24.6 (14.7) mg: 13.8 (9.4) mg on maintenance and 29.9 (14.3) mg on bursts. During the 6-month follow-up period, mean (SD) daily dose in the total cohort was 22.5 (18.8) mg: 17.2 (18.6) mg on maintenance and 28.4 (20.6) mg on bursts. The overall annual severe exacerbations rate during the 12-month baseline period was 2.05 per patient-year and 1.5 per patient-year over the 6-month follow-up, and frequency of hospitalizations and emergency department visits were similar on both maintenance and bursts use. CONCLUSIONS: Results show a suboptimal control of severe asthma despite such high doses of OCS and persistence of disease burden regardless of the prescribing pattern in maintenance or bursts. There is therapeutic inertia to continue using OCS despite the increased risk of adverse effects and the availability of biologics.

Short-Acting Beta-2-Agonist Exposure and Severe Asthma Exacerbations: SABINA Findings From Europe and North America.

BACKGROUND: Expert national/global asthma management recommendations raise the issue whether a safe threshold of short-acting beta-2 agonist (SABA) use without concomitant inhaled corticosteroids (ICS) exists. OBJECTIVE: To examine SABA and maintenance therapy associations with severe asthma exacerbations across North America and Europe. METHODS: Observational analyses of 10 SABa use IN Asthma (SABINA) datasets involving 1,033,564 patients (≥12 y) from Canada, France, the Netherlands, Poland, Spain, the United Kingdom, and the United States. Negative binomial models (incidence rate ratio [IRR] [95% CI adjusted for prespecified-covariates]) evaluated associations between SABA and exacerbations. RESULTS: Across severities, 40.2% of patients were prescribed/possessed 3 or more SABA canisters/y. Per the Global Initiative for Asthma (GINA) 2018 definitions, steps 3 to 5-treated patients prescribed/possessing 3 or more versus 1 or 2 SABAs experienced more severe exacerbations (IRR 1.08 [95% CI 1.04‒1.13], U.S. Medicare; IRR 2.11 [95% CI 1.96‒2.27], Poland). This association was not observed in all step 1 or 2-treated patients (the Netherlands, IRR 1.25 [95% CI 0.91‒1.71]; U.S. commercial, IRR 0.92 [95% CI 0.91‒0.93]; U.S. Medicare, IRR 0.74 [95% CI 0.71‒0.76]). We hypothesize that this inverse association between SABA and severe exacerbations in the U.S. datasets was attributable to the large patient population possessing fewer than 3 SABA and no maintenance therapy and receiving oral corticosteroid bursts without face-to-face health care provider encounters. In U.S. SABA monotherapy-treated patients, 3 or more SABAs were associated with more emergency/outpatient visits and hospitalizations (IRR 1.31 [95% CI 1.29‒1.34]). Most GINA 2 to 5-treated study patients (60.6%) did not have maintenance therapy for up to 50% of the time; however, the association of 3 or more SABAs and severe exacerbations persisted (IRR 1.32 [95% CI 1.18‒1.49]) after excluding these patients and the independent effect was further confirmed when U.K. SABA data were analyzed as a continuous variable in patients with up to 100% annual coverage for ICS-containing medications. CONCLUSIONS: Increasing SABA exposure is associated with severe exacerbation risk, independent of maintenance therapy. As addressed by GINA, based on studies across asthma severities where as-needed fast-acting bronchodilators with concomitant ICS decrease severe exacerbations compared with SABA, our findings highlight the importance of avoiding a rescue/reliever paradigm utilizing SABA monotherapy.

Real-world study in severe eosinophilic asthma patients refractory to anti-IL5 biological agents treated with benralizumab in Spain (ORBE study).

BACKGROUND: Benralizumab, a monoclonal antibody targeting the human interleukin-5 (IL-5) receptor (IL-5R), was used before marketing authorisation in Spain in a real world setting as part of an early-access programme (EAP) to treat patients with severe eosinophilic asthma with prior insufficient response or intolerance to anti-IL5 treatment (mepolizumab or reslizumab). The objective of this study is to describe the patient profile candidate for treatment and to assess benralizumab effectiveness. METHODS: This is an observational, retrospective, multicentre study in severe eosinophilic asthma patients refractory to other biological agents targeting the IL-5 pathway. Baseline characteristics included closest data, from the previous 12 months, to benralizumab treatment onset (index date). Patients were followed until the last treatment dosage while EAP was active (March to December 2018). Effectiveness was evaluated versus baseline, in patients who received at least three doses, with asthma control test (ACT), Mini Asthma Quality of Life Questionnaire (MiniAQLQ), annual severe exacerbation rate, oral corticosteroids treatment (OCS) and asthma-related healthcare resources utilization. RESULTS: Twenty-seven patients treated with benralizumab were included in the analysis. Effectiveness was assessed in 19 patients. Both questionnaires showed clinically meaningful differences, i.e. ACT score ≥ 3 and MiniAQLQ score ≥ 0.5, compared with baseline [mean (SD), 3.3 (6.8) and 1.2 (1.9), respectively]. Patients treated with OCS decreased during follow-up from 88.9% (n = 24/27) at baseline to 78.9% (n = 15/19) and 31.6% (n = 6/19) had an OCS dose reduction ≥ 50%. The difference in annual severe exacerbation rate during follow-up showed a significant reduction vs. baseline (2.12 per patient-year, 95% CI 0.99-3.24, p = 0.002). The differences in annual rate of non-scheduled primary care and specialist visits during follow-up indicated a significant decrease [2.28 per patient-year (95% CI 1.55-3.01; p < 0.001) and 1.47 per patient-year (95% CI 0.65-2.30; p = 0.004), respectively], as well as the difference in annual rate of number of emergency department visits [1.18 per patient-year (95% CI 0.51-1.85; p = 0.007)]. CONCLUSIONS: These results suggest that severe eosinophilic asthma patients receiving benralizumab, presented clinically meaningful improvement in asthma control and asthma-related QoL as well as OCS dose reduction. Results also aim to significant reductions in annual severe exacerbation rates, non-scheduled primary care and specialist visits, and emergency department visits rates.

Heterogeneity within and between physician-diagnosed asthma and/or COPD: NOVELTY cohort.

BACKGROUND: Studies of asthma and chronic obstructive pulmonary disease (COPD) typically focus on these diagnoses separately, limiting understanding of disease mechanisms and treatment options. NOVELTY is a global, 3-year, prospective observational study of patients with asthma and/or COPD from real-world clinical practice. We investigated heterogeneity and overlap by diagnosis and severity in this cohort. METHODS: Patients with physician-assigned asthma, COPD or both (asthma+COPD) were enrolled, and stratified by diagnosis and severity. Baseline characteristics were reported descriptively by physician-assigned diagnosis and/or severity. Factors associated with physician-assessed severity were evaluated using ordinal logistic regression analysis. RESULTS: Of 11 243 patients, 5940 (52.8%) had physician-assigned asthma, 1396 (12.4%) had asthma+COPD and 3907 (34.8%) had COPD; almost half were from primary care. Symptoms, health-related quality of life and spirometry showed substantial heterogeneity and overlap between asthma, asthma+COPD and COPD, with 23%, 62% and 64% of patients, respectively, having a ratio of post-bronchodilator forced expiratory volume in 1 s to forced vital capacity below the lower limit of normal. Symptoms and exacerbations increased with greater physician-assessed severity and were higher in asthma+COPD. However, 24.3% with mild asthma and 20.4% with mild COPD had experienced ≥1 exacerbation in the past 12 months. Medication records suggested both under-treatment and over-treatment relative to severity. Blood eosinophil counts varied little across diagnosis and severity groups, but blood neutrophil counts increased with severity across all diagnoses. CONCLUSION: This analysis demonstrates marked heterogeneity within, and overlap between, physician-assigned diagnosis and severity groups in patients with asthma and/or COPD. Current diagnostic and severity classifications in clinical practice poorly differentiate between clinical phenotypes that may have specific risks and treatment implications.

Observational studies assessing the pharmacological treatment of obstructive lung disease: strengths, challenges and considerations for study design.

Randomised controlled trials (RCTs) are the gold standard for evaluating treatment efficacy in patients with obstructive lung disease. However, due to strict inclusion criteria and the conditions required for ascertaining statistical significance, the patients included typically represent as little as 5% of the general obstructive lung disease population. Thus, studies in broader patient populations are becoming increasingly important. These can be randomised effectiveness trials or observational studies providing data on real-world treatment effectiveness and safety data that complement efficacy RCTs. In this review we describe the features associated with the diagnosis of asthma and chronic obstructive pulmonary disease (COPD) in the real-world clinical practice setting. We also discuss how RCTs and observational studies have reported opposing outcomes with several treatments and inhaler devices due to differences in study design and the variations in patients recruited by different study types. Whilst observational studies are not without weaknesses, we outline recently developed tools for defining markers of quality of observational studies. We also examine how observational studies are capable of providing valuable insights into disease mechanisms and management and how they are a vital component of research into obstructive lung disease. As we move into an era of personalised medicine, recent observational studies, such as the NOVEL observational longiTudinal studY (NOVELTY), have the capacity to provide a greater understanding of the value of a personalised healthcare approach in patients in clinical practice by focussing on standardised outcome measures of patient-reported outcomes, physician assessments, airway physiology, and blood and airway biomarkers across both primary and specialist care.

Real-life retrospective observational study to determine the prevalence and economic burden of severe asthma in Spain.

Objective: We determined the percentage of patients with severe asthma and exacerbations and evaluated the costs of the disease based on blood eosinophil counts.Methods: A retrospective observational study based on the review of medical records in Spain was carried out. Patients ≥18 years of age requiring care during the years 2014-2015; diagnosed with asthma with at least 2 years of continuous records (at least one year prior to the index date defined as the first asthma medication prescription and at least one year after the index date) were included. Study groups: eosinophil counts <300 cells/µl and ≥300 cells/µl. Main variables: comorbidity, clinical parameters, exacerbations and annual asthma total costs.Results: A total of 268 severe asthmatic patients in Spain were included, representing 6.3% of the asthma population, with 58.6% having eosinophil count ≥300 cells/µl and 41.4% eosinophil count <300 cells/µl. The mean age was 56.1 years (63.4% women). Patients with eosinophilic inflammation (≥300 cells/µl) had lower FEV1 values (54.3% vs. 60.7%; p < .001), poorer treatment adherence (65.6% vs. 77.3%; p < .001), and a greater mean number of exacerbations (3.3 vs. 1.9; p < .001). Exacerbations were correlated to FEV1 (ß=‒.606), eosinophils (ß = .255), immunoglobulin E (ß = .152), and age (ß = .128), p < .001. The mean total asthma annual cost (ANCOVA) was 6222 vs. 4152 euros, respectively (p = .016). Health costs were associated with age (ß = .323), FEV1 (ß = .239), eosinophils (ß = .177) and exacerbations (ß = .158), p < .01.Limitations: Those inherent to retrospective studies; the possible inaccuracy of diagnostic coding referring to severe asthma and other comorbidities and the external validity of the results.Conclusions: Health costs of patients with severe asthma were high. Total annual asthma costs and resource use were greater in patients with ≥300 cells/µl. Age, eosinophilia, exacerbations and FEV1 were associated with greater resource utilization and costs for the health system.

SABINA: An Overview of Short-Acting ß2-Agonist Use in Asthma in European Countries.

INTRODUCTION: Globally, individuals with asthma tend to overrely on short-acting ß2-agonists (SABAs) and underuse inhaled corticosteroids, thereby undertreating the underlying inflammation. Such relief-seeking behavior has been reinforced by long-standing treatment guidelines, which until recently recommended SABA-only use for immediate symptom relief. We aimed to describe the current burden of SABA use among European individuals with asthma within the SABA use IN Asthma (SABINA) program. METHODS: Prescription and/or dispensing data during 2006-2017 from electronic medical records and/or national patient registries in the United Kingdom (UK), Germany, Italy, Spain, and Sweden were analyzed. Individuals aged at least 12 years old with a current asthma diagnosis and no other chronic respiratory conditions were included. Asthma treatment step and severity were based on treatment guidelines in use in each individual country. The proportion of individuals prescribed SABA was measured during a 12-month period. SABA overuse was defined as at least three SABA canisters per year. RESULTS: More than one million individuals with asthma were included across five European countries. Overall, the majority of individuals were over 45 years of age, except in Sweden (mean age 27.6 years) where individuals aged over 45 years were excluded to avoid a potential chronic obstructive pulmonary disease co-diagnosis. The study population was predominantly female (55-64%), except in the UK (46%). The prevalence of SABA overuse was 9% in Italy, 16% in Germany, 29% in Spain, 30% in Sweden, and 38% in the UK. In the UK, SABA overuse was greater in individuals with moderate-to-severe asthma versus individuals with mild asthma (58% versus 27%, respectively), while SABA overuse was similar in individuals with both mild (9-32%) and moderate-to-severe (8-31%) asthma in the other European countries. CONCLUSIONS: The findings of this study from the SABINA program show that SABA overuse (at least three canisters per year) is common across Europe, despite the different healthcare and reimbursement policies of each country.

Use of aclidinium did not increase the risk of death in a noninterventional cohort study in the Clinical Practice Research Datalink (CPRD), United Kingdom.

BACKGROUND: Aclidinium bromide is an inhaled long-acting muscarinic antagonist (LAMA). Although the initial potential increased cardiovascular and mortality risk among users of tiotropium has been ruled out by several observational studies, and clinical trials, there are still concerns related to the use of newer LAMA medications. The current study aimed to evaluate the risk of death among users of aclidinium and other LAMAs. METHODS: We conducted a cohort and nested case-control study among patients with COPD aged 40 years or older to compare the risk of all-cause mortality among users of aclidinium and other COPD medications with the risk among users of long-acting ß2 agonists (LABA), in the Clinical Practice Research Datalink (CPRD) in the United Kingdom (2012-2017). RESULTS: Mortality rates per 1,000 person-years were 32.9 for aclidinium, 43.8 for tiotropium, 38.0 for other LAMA, 47.1 for LABA/ICS, and 38.1 for LABA. The RR of death compared with current use of LABA was 0.54 (confidence interval [95% CI], 0.40-0.72) for aclidinium, 0.96 (95% CI, 0.76-1.21) for tiotropium, 0.76 (95% CI, 0.58-0.99) for other LAMA, and 1.08 (95% CI, 0.90-1.31) for LABA/ICS. Decreased risk for death observed among users of aclidinium was driven by overall current single use (RR = 0.41; 95% CI, 0.22-0.79), which corresponded to 26% of the aclidinium users (<15 cases) and not by multiple use (RR = 1.02; 95% CI, 0.71-1.48). CONCLUSION: Use of aclidinium, tiotropium, other LAMA, or LABA/ICS was not associated with an increased risk of all-cause mortality as compared with the use of LABAs.

Prospective observational study in patients with obstructive lung disease: NOVELTY design.

Asthma and chronic obstructive pulmonary disease (COPD) have overlapping clinical features and share pathobiological mechanisms but are often considered distinct disorders. Prospective, observational studies across asthma, COPD and asthma-COPD overlap are limited. NOVELTY is a global, prospective observational 3-year study enrolling ∼12 000 patients ≥12 years of age from primary and specialist clinical practices in 19 countries (ClinicalTrials.gov identifier: NCT02760329). NOVELTY's primary objectives are to describe patient characteristics, treatment patterns and disease burden over time, and to identify phenotypes and molecular endotypes associated with differential outcomes over time in patients with a diagnosis/suspected diagnosis of asthma and/or COPD. NOVELTY aims to recruit real-world patients, unlike clinical studies with restrictive inclusion/exclusion criteria. Data collected at yearly intervals include clinical assessments, spirometry, biospecimens, patient-reported outcomes (PROs) and healthcare utilisation (HCU). PROs and HCU will also be collected 3-monthly via internet/telephone. Data will be used to identify phenotypes and endotypes associated with different trajectories for symptom burden, clinical progression or remission and HCU. Results may allow patient classification across obstructive lung disease by clinical outcomes and biomarker profile, rather than by conventional diagnostic labels and severity categories. NOVELTY will provide a rich data source on obstructive lung disease, to help improve patient outcomes and aid novel drug development.

The economic burden of uncontrolled gout: how controlling gout reduces cost.

AIM: To evaluate the burden of uncontrolled gout by examining estimated costs and cost drivers. MATERIALS AND METHODS: Data from the 2012 and 2013 US National Health and Wellness Survey (NHWS; 2012 NHWS, n = 71,157 and 2013 NHWS, n = 75,000) were utilized in this study. Based on self-reported gout diagnosis and gout symptoms, respondents were categorized into three groups: controlled gout (n = 344), uncontrolled gout (n = 2,215), and non-gout controls (n = 126,360). Chi-square tests and one-way analysis of variance (ANOVAs) were used to assess group differences on work productivity loss, healthcare resource utilization, and costs. Zero-inflated negative binomial regressions were used to assess the burden of uncontrolled gout on total costs after controlling for covariates. RESULTS: Patients with uncontrolled gout had higher presenteeism, overall work impairment, activity impairment, and number of emergency department visits than those with controlled gout or controls. Overall, uncontrolled gout patients had both higher indirect and total costs compared to patients with controlled gout. After controlling for confounders, those with uncontrolled gout had higher total costs than controlled gout respondents and non-gout controls; there was no significant difference in total costs between patients with controlled gout and non-gout controls. LIMITATIONS: Results were based on cross-sectional, self-reported data, making causal inferences more uncertain. Additionally, sample size was small for controlled-gout respondents. Lastly, sampling weights were not used, thus potentially limiting generalizability. CONCLUSION: Gout can be an expensive condition, particularly if it is not properly controlled. This study provides support that controlling symptoms (e.g. flares) can reduce the economic and societal burden of gout. Therefore, more attention needs to be paid to effective management of gout symptoms.

Association between blood eosinophil count and risk of readmission for patients with asthma: Historical cohort study.

BACKGROUND: Recent studies have demonstrated an association between high blood eosinophil counts and greater risk of asthma exacerbations. We sought to determine whether patients hospitalized for an asthma exacerbation were at greater risk of readmission if they had a high blood eosinophil count documented before the first hospitalization. METHODS: This historical cohort study drew on 2 years of medical record data (Clinical Practice Research Datalink with Hospital Episode Statistics linkage) of patients (aged ≥5 years) admitted to hospital in England for asthma, with recorded blood eosinophil count within 1 baseline year before admission. We analyzed the association between high blood eosinophil count (≥0.35x109 cells/L) and readmission risk during 1 year of follow-up after hospital discharge, with adjustment for predefined, relevant confounders using forward selection. RESULTS: We identified 2,613 eligible patients with asthma-related admission, of median age 51 years (interquartile range, 36-69) and 76% women (1,997/2,613). Overall, 835/2,613 (32.0%) had a preadmission high blood eosinophil count. During the follow-up year, 130/2,613 patients (5.0%) were readmitted for asthma, including 55/835 (6.6%) with vs. 75/1,778 (4.2%) without high blood eosinophil count at baseline (adjusted hazard ratio [HR] 1.49; 95% CI 1.04-2.13, p = 0.029). The association was strongest in never-smokers (n = 1,296; HR 2.16, 95% CI 1.27-3.68, p = 0.005) and absent in current smokers (n = 547; HR 1.00, 95% CI 0.49-2.04, p = 0.997). CONCLUSIONS: A high blood eosinophil count in the year before an asthma-related hospitalization is associated with increased risk of readmission within the following year. These findings suggest that patients with asthma and preadmission high blood eosinophil count require careful follow-up, with treatment optimization, after discharge.

The impacts of morning, daytime, and nighttime symptoms on disease burden in real-world patients with COPD.

Background: Respiratory symptoms are increasingly recognized as an important consideration in COPD management. Understanding the links between the time(s) of day symptoms are experienced and overall symptom burden could support personalized management strategies. This real-world study aimed to establish the association between the time of day of symptoms and the burden on patients using validated patient-reported outcomes, health care resource utilization, and physician-perceived impact of COPD on patients' lives. Materials and methods: Analyses used data from four waves (2012, 2013, 2014, and 2016) of the Respiratory Disease Specific Programme: cross-sectional surveys of patients with COPD in Germany, Italy, Spain, and the UK. Patients were classified by their physicians as having symptoms in the morning (M), daytime (D), and/or nighttime (N) in the 4 weeks before entering the Disease Specific Programme. Outcomes included health care resource utilization, work productivity and activity impairment, COPD Assessment Test, EuroQol 5-dimension 3-level questionnaire with visual analog scale, and Jenkins Sleep Evaluation Questionnaire. Results: In total, 8,844 patients were included, and 8,185 had evaluable time-of-day symptom data. Physicians reported that in the previous 4 weeks, 25% of patients experienced no symptoms, 16% D only, 17% M/D only, 6% D/N only, 4% M, N, or M/N only, and 32% M/D/N. In general, patients with M/D/N symptoms utilized more health care resources in the previous 12 months, had more prior exacerbations, and reported worse activity impairment, health status, and sleep than other symptom groups, whereas patients with symptoms at any time of the day utilized more resources, experienced more exacerbations, and reported worse health status than patients with no symptoms during the 4 weeks before entering the survey. Conclusion: Patients experiencing morning, daytime, and nighttime symptoms experience a greater disease burden than those in other groups. An individualized approach to COPD treatment based on the timing and persistence of symptoms may improve outcomes for these patients.

Serum uric acid levels are associated with cardiovascular risk score: A post hoc analysis of the EURIKA study.

BACKGROUND: Reports are conflicting on whether serum uric acid (sUA) levels are independently associated with increased cardiovascular (CV) death risk. METHODS: This post hoc analysis assessed the relationship between sUA levels and CV death risk score in 7531 patients from the cross-sectional, multinational EURIKA study (NCT00882336). Patients had at least one CV risk factor but no clinical CV disease. Ten-year risk of CV death was estimated using SCORE-HDL and SCORE algorithms, categorized as low (<1%), intermediate (1% to <5%), high (≥5% to <10%) or very high (≥10%). RESULTS: Mean serum sUA levels increased significantly with increasing CV death risk category in the overall population and in subgroups stratified by diuretics use or renal function (all P<0.0001). Multivariate ordinal logistic regression analyses, adjusted for factors significantly associated with CV death risk in univariate analyses (study country, body mass index, number of CV risk factors and comorbidities, use of lipid lowering therapies, antihypertensives and antidiabetics), showed a significant association between sUA levels and SCORE-HDL category in the overall population (OR: 1.39 [95% CI: 1.34-1.44]) and all subgroups (using diuretics: 1.32 [1.24-1.40]; not using diuretics: 1.46 [1.39-1.53]; estimated glomerular filtration rate [eGFR]<60ml/min/1.73m2: 1.30 [1.22-1.38]; eGFR≥60ml/min/1.73m2: 1.44 [1.38-1.51]; all P<0.0001). Similar results were obtained when using SCORE. CONCLUSIONS: Higher sUA levels are associated with progressively higher 10-year CV death risk score in patients with at least one CV risk factor but no CV disease.

Any link of gout disease control among hypertensive patients and onset of end-stage renal disease? Results from a population-based study.

AIM: To determine the impact of allopurinol non-adherence as a proxy for uncontrolled disease on primary prevention of end-stage renal disease (ESRD). METHODS: A cohort of 2752 patients with gout diagnosis was reconstructed using the Québec Régie de l'assurance maladie du Québec and MedEcho administrative databases. Eligible patients were new users of allopurinol, aged 45-85, with a diagnosis of hypertension, and treated with an antihypertensive drug between 1997 and 2007. RESULTS: Major risk factor for ESRD onset was chronic kidney disease at stages 1 to 3 [rate ratio (RR) = 8.00; 95% confidence interval (CI): 3.16-22.3 and the severity of hypertension (≥ 3 vs < 3 antihypertensives)] was a trending risk factor as a crude estimate (RR = 1.94; 95%CI: 0.68-5.51). Of 341 patients, cases (n = 22) and controls (n = 319), high adherence level (≥ 80%) to allopurinol therapy, compared with lower adherence level (< 80%), was associated with a lower rate of ESRD onset (RR = 0.35; 95%CI: 0.13-0.91). CONCLUSION: Gout control seem to be associated with a significant decreased risk of ESRD onset in hypertensive populations, further research should be conducted confirming this potential associated risk.

Disease Control, Health Resource Use, Healthcare Costs, and Predictors in Gout Patients in the United States, the United Kingdom, Germany, and France: A Retrospective Analysis.

INTRODUCTION: The present study aimed to assess disease control, health resource utilization (HRU), and healthcare costs, and their predictors in gout patients across the USA, UK, Germany, and France. METHODS: Data were extracted from the PharMetrics Plus (USA), Clinical Practice Research Datalink-Hospital Episode Statistics (UK), and Disease Analyzer databases (Germany and France) for adult gout patients over a 3-year period: 2009-2011 (all dates +1 year for France). Patients had "prevalent established gout" (i.e., were treated with urate-lowering therapy [ULT] or eligible for ULT based on American College of Rheumatology guidelines) in the preindex panel-year, with January 1 of the second study year as the study index date. Assessments of disease control (uncontrolled gout definition: ≥1 serum urate (sUA) elevation or ≥2 flares; analysis limited to the subpopulation with sUA) data, HRU, and costs were in the second post-index panel-year, while potential predictors (demographics and gout treatment characteristics) were identified in the first post-index panel-year. RESULTS: Treatment rates were high (>70% with chronic urate-lowering treatment in all countries but France), while between 31.3% (France) and 62.9% (USA) of patients remained uncontrolled. Predictors of control included female gender and high adherence. In Germany, the UK, and France, lack of disease control predicted increased gout-attributed costs and increased HRU, both gout-attributed (also in the USA) and non-gout-attributed. CONCLUSION: Gout management remains suboptimal, as many patients remain uncontrolled despite using urate-lowering treatment. Effective and convenient treatment options are needed to improve disease control and minimize additional HRU and costs. FUNDING: AstraZeneca.