Impact of COPD diagnosis timing on clinical and economic outcomes: the ARCTIC observational cohort study.

Purpose: Assess the clinical and economic consequences associated with an early versus late diagnosis in patients with COPD. Patients and methods: In a retrospective, observational cohort study, electronic medical record data (2000-2014) were collected from Swedish primary care patients with COPD. COPD indicators (pneumonia, other respiratory diseases, oral corticosteroids, antibiotics for respiratory infections, prescribed drugs for respiratory symptoms, lung function measurement) registered prior to diagnosis were applied to categorize patients into those receiving early (2 or less indicators) or late diagnosis (3 or more indicators registered >90 days preceding a COPD diagnosis). Outcome measures included annual rate of and time to first exacerbation, mortality risk, prevalence of comorbidities and health care utilization. Results: More patients with late diagnosis (n=8827) than with early diagnosis (n=3870) had a recent comorbid diagnosis of asthma (22.0% vs 3.9%; P<0.0001). Compared with early diagnosis, patients with late diagnosis had a higher exacerbation rate (hazard ratio [HR] 1.89, 95% confidence interval [CI]: 1.83-1.96; P<0.0001) and shorter time to first exacerbation (HR 1.61, 95% CI: 1.54-1.69; P<0.0001). Mortality was not different between groups overall but higher for late versus early diagnosis, after excluding patients with past asthma diagnosis (HR 1.10, 95% CI: 1.02-1.18; P=0.0095). Late diagnosis was also associated with higher direct costs than early diagnosis. Conclusion: Late COPD diagnosis is associated with higher exacerbation rate and increased comorbidities and costs compared with early diagnosis. The study highlights the need for accurate diagnosis of COPD in primary care in order to reduce exacerbations and the economic burden of COPD.

Patients' perspectives on COPD: findings from a social media listening study.

We utilised social media listening (SML) to obtain patients' perspectives on symptoms, diagnosis and comorbidities associated with chronic obstructive pulmonary disease (COPD) and its impact on patients' quality of life (QoL). A comprehensive search on social media platforms was performed for English language content posted between July 2016 and January 2018 using COPD-related terms. Social Studio, a social media data aggregator tool, was used to capture relevant records. The content was manually curated to analyse and map psychological aspects with descriptive statistics applied on aggregated findings. A total of 849 posts from patients or caregivers ("patient insights") were considered for the analysis, corresponding to postings of 695 unique individuals. Based on 734 mentions of symptoms from 849 posts by potential patients/caregivers, cough (27%), mucus (25%) and shortness of breath (21%) were the most frequent; analysis by perceived COPD severity indicated these to be common across all severities. Difficulty in mucus clearance (24% of 268 mentions) and sadness (40% of 129 mentions) were top among the aspects impacting physical and emotional QoL, respectively. SML from patients with COPD indicated that relief from cough, mucus production and shortness of breath would be the most desirable aspects of disease management from a patient's perspective.

COPD uncovered: a cross-sectional study to assess the socioeconomic burden of COPD in Japan.

Background: COPD remains a major health problem in Japan. Patients with COPD experience a reduced quality of life (QoL) and have a higher chance of work impairment and productivity loss. However, there is a lack of data on the impact of COPD in terms of QoL and work activity impairment in Japan. This study assessed the socioeconomic burden of COPD in Japan and the impact it may have on the working age population. Patients and methods: This was a 2-year retrospective chart review in COPD patients aged ≥40 years, with at least one health care visit to clinic or hospital in the previous 12 months. Patients were required to have available medical charts for at least the previous 24 months. Symptoms were assessed using COPD assessment test score; EuroQoL Group 5 Dimension (EQ-5D-5L) and work productivity and activity impairment general health questionnaires were used to evaluate health-related QoL and work productivity, and health care resource utilization data were obtained from clinical charts. Results: In total, 71 patients aged <65 years, and 151 patients aged ≥65 years were included; the majority of patients had moderate or severe airflow limitation. Exacerbations (moderate or severe) were reported by ~35% of patients in both age groups; 52.1% and 62.9% of patients in the <65-year and ≥65-year age groups had COPD assessment test scores ≥10. EQ-5D-5L index scores in the <65-year and ≥65-year age groups were 0.79 and 0.77, respectively. Work productivity and activity impairment scores were higher in <65-year age group. Annual costs of health care resource use per patient in the <65-year and ≥65-year age groups were ¥438,975 (US$4,389) and ¥467,871 (US$4,678), respectively. Costs due to productivity loss were estimated to be ¥5,287,024 (US$52,870) in the <65-year age group and ¥3,018,974 (US$30,187) in the ≥65-year age group. Conclusion: COPD represents a significant socioeconomic burden in Japan. Patients with COPD report significant use of health care resources. Higher impact on work impairment and productivity loss was observed frequently in the working age population.

Real-world retrospective cohort study ARCTIC shows burden of comorbidities in Swedish COPD versus non-COPD patients.

This study aimed to generate real-world evidence to assess the burden of comorbidities in COPD patients, to effectively manage these patients and optimize the associated healthcare resource allocation. ARCTIC is a large, real-world, retrospective cohort study conducted in Swedish COPD patients using electronic medical record data collected between 2000 and 2014. These patients were studied for prevalence of various comorbidities and for association of these comorbidities with exacerbations, mortality, and healthcare costs compared with an age-, sex-, and comorbidities-matched non-COPD reference population. A total of 17,479 patients with COPD were compared with 84,514 non-COPD reference population. A significantly higher prevalence of various comorbidities was observed in COPD patients 2 years post-diagnosis vs. reference population, with the highest percentage increase observed for cardiovascular diseases (81.8% vs. 30.7%). Among the selected comorbidities, lung cancer was relatively more prevalent in COPD patients vs. reference population (relative risk, RR = 5.97, p < 0.0001). Ischemic heart disease, hypertension, depression, anxiety, sleep disorders, osteoporosis, osteoarthritis, and asthma caused increased mortality rates in COPD patients. Comorbidities that were observed to be significantly associated with increased number of severe exacerbations in COPD patients included heart failure, ischemic heart disease, depression/anxiety, sleep disorders, osteoporosis, lung cancer, and stroke. The cumulative healthcare costs associated with comorbidities over 2 years after the index date were observed to be significantly higher in COPD patients (€27,692) vs. reference population (€5141) (p < 0.0001). The data support the need for patient-centered treatment strategies and targeted healthcare resource allocation to reduce the humanistic and economic burden associated with COPD comorbidities.

Economic burden of COPD in a Swedish cohort: the ARCTIC study.

Background: We assessed direct and indirect costs associated with COPD in Sweden and examined how these costs vary across time, age, and disease stage in a cohort of patients with COPD and matched controls in a real-world, primary care (PC) setting. Patients and methods: Data from electronic medical records linked to the mandatory national health registers were collected for COPD patients and a matched reference population in 52 PC centers from 2000 to 2014. Direct health care costs (drug, outpatient or inpatient, PC, both COPD related and not COPD related) and indirect health care costs (loss of income, absenteeism, loss of productivity) were assessed. Results: A total of 17,479 patients with COPD and 84,514 reference controls were analyzed. During 2013, direct costs were considerably higher among the COPD patient population (€13,179) versus the reference population (€2,716), largely due to hospital nights unrelated to COPD. Direct costs increased with increasing disease severity and increasing age and were driven by higher respiratory drug costs and non-COPD-related hospital nights. Indirect costs (~€28,000 per patient) were the largest economic burden in COPD patients of working age during 2013. Conclusion: As non-COPD-related hospital nights represent the largest direct cost, management of comorbidities in COPD would offer clinical benefits and relieve the financial burden of disease.

Greater dyspnea is associated with lower health-related quality of life among European patients with COPD.

OBJECTIVE: Dyspnea is a defining symptom in the classification and treatment of chronic obstructive pulmonary disease (COPD). However, the degree of variation in burden among symptomatic COPD patients and the possible correlates of burden remain unclear. This study was conducted to characterize patients in Europe currently being treated for COPD according to the level of dyspnea in terms of sociodemographics, health-related quality of life, work productivity impairment, and health care resource use assessed by patient reports. METHODS: Data were derived from the 5-EU 2013 National Health and Wellness Survey (N=62,000). Respondents aged ≥40 years who reported currently using a prescription for COPD were grouped according to their level of dyspnea as per the Global Initiative for Chronic Obstructive Lung Disease guidelines and compared on health status (revised Short Form 36 [SF-36]v2), work impairment (Work Productivity and Activity Impairment questionnaire), and number of health care visits in the past 6 months using generalized linear models with appropriate distributions and link functions. RESULTS: Of the 768 respondents who met the inclusion criteria, 245 (32%) were considered to have higher dyspnea (equivalent to modified Medical Research Council score ≥2). Higher dyspnea was associated with decrements ranging from 3.9 to 8.2 points in all eight domains of the SF-36 health profile after adjustment for sociodemographics, general health characteristics, and length of COPD diagnosis; mental component summary scores and Short Form-6D health utility scores were lower by 3.5 and 0.06 points, respectively. Adjusted mean activity impairment (55% vs 37%, P<0.001) and number of emergency room visits (0.61 vs 0.40, P=0.030) were higher in patients with greater dyspnea. CONCLUSION: Many European patients with COPD continue to experience dyspnea despite treatment and at levels associated with notable impairments in the patients' ability to function across a multitude of domains. These patients may benefit from more intense treatment of their symptoms.

Comparative efficacy of long-acting ß2-agonists as monotherapy for chronic obstructive pulmonary disease: a network meta-analysis.

PURPOSE: Long-acting ß2-agonists (LABAs) have demonstrated efficacy in patients with COPD in clinical trials. The purpose of this study was to assess the comparative efficacy of all available dosages of all LABA monotherapies using a network meta-analysis. METHODS: A systematic literature review identified 33 randomized controlled trials of LABA monotherapies (salmeterol 50 µg twice daily [BID]; formoterol 12 µg BID; indacaterol 75, 150, and 300 µg once daily [OD]; olodaterol 5 and 10 µg OD, and vilanterol 25 µg OD). Clinical efficacy was evaluated at 12 and 24 weeks in terms of trough forced expiratory volume in 1 second (FEV1), transition dyspnea index focal score, St George's Respiratory Questionnaire total score, and rate of COPD exacerbations. The relative effectiveness of all LABA monotherapies was estimated by Bayesian network meta-analysis. RESULTS: At 12 and 24 weeks, indacaterol 300 and 150 µg OD were associated with statistically significant improvement in trough FEV1 compared to all other LABA monotherapies; vilanterol 25 µg OD was superior to formoterol 12 µg BID. At 12 weeks, indacaterol 75 µg OD was associated with significant improvement in trough FEV1 compared to formoterol 12 µg BID and olodaterol (5 and 10 µg OD); salmeterol 50 µg BID was superior to formoterol 12 µg BID and olodaterol 5 µg OD. Indacaterol 300 µg OD was also associated with significant improvement in transition dyspnea index focal score compared to all other LABAs at 12 or 24 weeks. Indacaterol 150 µg OD had significantly better results in exacerbation rates than olodaterol 5 µg and olodaterol 10 µg OD. CONCLUSION: Indacaterol 300 µg, followed by 150 and 75 µg, were the most effective LABA monotherapies for moderate to severe COPD.

Cost Effectiveness of the Long-Acting ß2-Adrenergic Agonist (LABA)/Long-Acting Muscarinic Antagonist Dual Bronchodilator Indacaterol/Glycopyrronium Versus the LABA/Inhaled Corticosteroid Combination Salmeterol/Fluticasone in Patients with Chronic Obstructive Pulmonary Disease: Analyses Conducted for Canada, France, Italy, and Portugal.

OBJECTIVE: The objective of this study was to assess the cost effectiveness of the dual bronchodilator indacaterol/glycopyrronium (IND/GLY) compared with salmeterol/fluticasone combination (SFC) in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD) who had a history of one or no exacerbations in the previous year, in Canada, France, Italy, and Portugal. METHODS: A patient-level simulation was developed to compare the costs and outcomes of IND/GLY versus SFC based on data from the LANTERN trial (NCT01709903). Monte-Carlo simulation methods were employed to follow individual patients over various time horizons. Population and efficacy inputs were derived from the LANTERN trial. Considering the payers' perspective, only direct costs were included. Costs and health outcomes were discounted annually at 3.0 % for all countries. Unit costs were taken from publically available sources with all costs converted to euros (€). The cost base year was 2015. Deterministic and probabilistic sensitivity analyses were undertaken to test the robustness of the model results. RESULTS: IND/GLY was found to be the dominant (more effective and less costly) treatment option compared with SFC in all four countries. The use of IND/GLY was associated with mean total cost savings per patient over a lifetime of €6202, €1974, €1611, and €220 in Canada, France, Italy, and Portugal, respectively. Sensitivity analysis showed that exacerbation rates had the largest impact on incremental costs and quality-adjusted life-years (QALYs). The probability of IND/GLY being cost effective was estimated to be >95 % for thresholds above €5000/QALY. CONCLUSION: In patients with moderate to severe COPD, IND/GLY is likely to be a cost-effective treatment alternative compared with SFC.

Cost-Effectiveness of Glycopyrronium Bromide Compared with Tiotropium in Patients with Chronic Obstructive Pulmonary Disease in Sweden.

OBJECTIVES: The objective of this study was to compare the cost effectiveness of once-daily Seebri Breezhaler(®) (glycopyrronium bromide) 50 µg with Spiriva(®) (tiotropium bromide) 18 µg in the maintenance treatment of chronic obstructive pulmonary disease (COPD) in the Swedish setting. METHODS: A previously published COPD Markov model accounting for disease progression and treatment discontinuation was used. Disease progression included the annual decline in forced expiratory volume in the first second (FEV1) and occurrence of any exacerbations. Efficacy in the model consisted of FEV1 improvement between baseline and 12 weeks and the annual risk ratio of having an exacerbation compared to placebo. These clinical efficacy inputs were derived from a 1-year head-to-head trial comparing glycopyrronium 50 µg to tiotropium 18 µg. Utility values and cost estimates were obtained from the literature. The base-case analysis was performed for a 3-year time horizon. Cost and effects were discounted with 3% in accordance to Swedish guidelines. Uncertainty was assessed by one-way and probabilistic sensitivity analyses. RESULTS: Glycopyrronium was found to be less costly and more effective than tiotropium in moderate to severe COPD patients with cost savings of 5197 Swedish kronor (€570, US$725) per patient over a 3-year time horizon. The probabilistic sensitivity analysis indicated that over 99% of the iterations produced dominant results for glycopyrronium. CONCLUSION: Glycopyrronium bromide 50 µg once daily can be considered a cost effective alternative to tiotropium bromide 18 µg once daily in the maintenance treatment of COPD patients in Sweden.

Cost-effectiveness of metformin plus vildagliptin compared with metformin plus sulphonylurea for the treatment of patients with type 2 diabetes mellitus: a Portuguese healthcare system perspective.

OBJECTIVE: To evaluate the cost-effectiveness of vildagliptin plus metformin vs generic sulphonylurea plus metformin in patients with type 2 diabetes mellitus, not controlled with metformin, from a Portuguese healthcare system perspective. METHODS: A cost-effectiveness model was constructed using risk equations from the UK Prospective Diabetes Study Outcomes Model with a 10,000-patient cohort and a lifetime horizon. The model predicted microvascular and macrovascular complications and mortality in yearly cycles. Patients entered the model as metformin monotherapy failures and switched to alternative treatments (metformin plus basal-bolus insulin and subsequently metformin plus intensive insulin) when glycated hemoglobin A1c >7.5% was reached. Baseline patient characteristics and clinical variables were derived from a Portuguese epidemiological study. Cost estimates were based on direct medical costs only. One-way and probabilistic sensitivity analyses were conducted to test the robustness of the model. RESULTS: There were fewer non-fatal diabetes-related adverse events (AEs) in patients treated with metformin plus vildagliptin compared with patients treated with metformin plus sulphonylurea (6752 vs 6815). Addition of vildagliptin compared with sulphonylurea led to increased drug acquisition costs but reduced costs of AEs, managing morbidities, and monitoring patients. Treatment with metformin plus vildagliptin yielded a mean per-patient gain of 0.1279 quality-adjusted life years (QALYs) and a mean per-patient increase in total cost of €1161, giving an incremental cost-effectiveness ratio (ICER) of €9072 per QALY. Univariate analyses showed that ICER values were robust and ranged from €4195 to €16,052 per QALY when different parameters were varied. LIMITATIONS: The model excluded several diabetes-related morbidities, such as peripheral neuropathy and ulceration, and did not model second events. Patients were presumed to enter the model with no diabetes-related complications. CONCLUSION: Treatment with metformin plus vildagliptin compared with metformin plus sulphonylurea is expected to result in a lower incidence of diabetes-related AEs and to be a cost-effective treatment strategy.

Medical resource use and costs associated with chylomicronemia.

BACKGROUND: The prevalence of severe hypertriglyceridemia (TG > 1000 mg/dl) is estimated at 150-400 per 100,000 individuals in North America. Severe hypertriglyceridemia in the fasting state is associated with increased acute pancreatitis risk and is a sign of chylomicronemia which reflects the accumulation in the bloodstream of chylomicrons, the large lipoprotein particles produced in the gut after a meal. OBJECTIVE: To assess medical resource use and costs associated with chylomicronemia. METHODS: Patients with chylomicronemia of different causes (≥2 diagnoses with ICD-9 code 272.3) were identified from a large US claims database (years 2000 to 2009) and matched 1:1 to controls free of chylomicronemia based on age, gender, demographics, comorbidities, and use of lipid lowering drugs. During a 1-year study period, medical resource use and costs associated with chylomicronemia or acute pancreatitis were compared between matched cases and controls. RESULTS: Among 6472 matched pairs, annual per-patient medical costs, calculated independently of the occurrence of acute pancreatitis, were significantly greater by $808 for chylomicronemia cases vs controls ($8029 vs $7220, p < 0.01), half of which was attributable to chylomicronemia-related services (p < 0.01). Chylomicronemia cases with a history of acute pancreatitis (n = 46) had greater rates of inpatient visits (p < 0.05) and greater average costs for subsequent acute pancreatitis or abdominal pain (p < 0.01) as well as greater total medical costs ($33,587 vs $4402, p < 0.01) vs matched controls. The average episode of acute pancreatitis (n = 104 episodes) generated medical costs of $31,820, almost entirely due to inpatient stays. LIMITATIONS: Triglyceride levels were not available to characterize disease severity. CONCLUSIONS: Patients with chylomicronemia, and especially those with a history of acute pancreatitis, incurred significantly greater total medical costs compared with individuals without chylomicronemia but with an otherwise comparable health profile.

Demonstrating the burden of hypoglycemia on patients' quality of life in diabetes clinical trials: measurement considerations for hypoglycemia.

OBJECTIVES: To evaluate the association between hypoglycemia and health-related quality of life (HRQoL) in the context of a clinical trial using both an objectively confirmed and a patient-reported measure of hypoglycemia. METHODS: During a phase III, double-arm, randomized study, patients completed the short form 36 health survey (SF-36), a generic HRQoL questionnaire, at baseline and at weeks 24, 52, and 104. The objectively confirmed measure of hypoglycemia was based on a combination of plasma glucose measure and presence of hypoglycemia-related symptoms. The patient-reported frequency of hypoglycemia was defined as the following item: "How often have you felt that your blood sugars have been unacceptably low recently?" The association between hypoglycemia and HRQoL was evaluated in intent-to-treat patients (N = 3059) by using repeated-measurements analyses, with SF-36 scores used as explained variables and baseline SF-36 score, age, sex, country, time, and either number of objectively confirmed hypoglycemic events (0, ≥1) or patient-reported frequency of hypoglycemia (continuous variable 0-6) as explanatory variables. RESULTS: During study duration, less than 6% of patients experienced at least one objectively confirmed hypoglycemic event and about half the patients reported unacceptably low blood sugars "none of the time." The association between the number of objectively confirmed hypoglycemic events and HRQoL was not statistically significant, while the patient-reported frequency of hypoglycemia was statistically significantly related to all SF-36 scores (P < 0.001), except physical functioning; patients reporting greater perceived frequency of hypoglycemia had worse HRQoL. CONCLUSIONS: Using a patient-reported measure of hypoglycemia in the context of a clinical trial could enable the burden of hypoglycemia for patients to be demonstrated.

Comparative efficacy of vildagliptin and sitagliptin in Japanese patients with type 2 diabetes mellitus: a matching-adjusted indirect comparison of randomized trials.

BACKGROUND AND OBJECTIVE: Vildagliptin and sitagliptin are oral dipeptidyl peptidase 4 inhibitors approved in Japan for the treatment of type 2 diabetes mellitus when adequate glycaemic control is not achieved with diet, exercise or sulphonylureas. The aim of this study was to compare 12-week glycaemic control with vildagliptin 50 mg twice daily versus sitagliptin 50 or 100 mg once daily in Japanese patients with type 2 diabetes. METHODS: Randomized trials of vildagliptin or sitagliptin in Japanese patients were identified from the literature. Individual patient data were obtained for vildagliptin trials. In the absence of a head-to-head randomized trial, a matching-adjusted indirect comparison was conducted by weighting individual patients from vildagliptin trials to match average baseline characteristics published for sitagliptin trials, including age, sex, body mass index, glycosylated haemoglobin (HbA(1c)), fasting plasma glucose (FPG) and diabetes duration. After matching, HbA(1c) change from baseline to week 12, the primary endpoint in each trial, was compared between balanced populations treated with vildagliptin and sitagliptin. Separate comparisons were conducted for vildagliptin 50 mg twice daily versus sitagliptin 50 mg and 100 mg once daily. RESULTS: Two trials of vildagliptin and three trials of sitagliptin were identified for Japanese patients. Across all included trials, a total of 264 patients were treated with vildagliptin 50 mg twice daily, 235 were treated with sitagliptin 50 mg once daily and 145 were treated with sitagliptin 100 mg once daily. Mean baseline HbA(1c) ranged from 7.4% to 7.8% per trial. Before matching, significant (p < 0.05) cross-trial differences included lower mean HbA(1c) (by 0.2-0.3%) and higher FPG (by 5-13 mg/dL) in vildagliptin trials. After matching, all baseline characteristics were balanced between treatment groups. Combining matched trials, vildagliptin 50 mg twice daily was associated with significantly greater absolute HbA(1c) reduction by 0.28% compared with sitagliptin 50 mg once daily (95% CI 0.15, 0.41; p < 0.001) and by 0.35% compared with sitagliptin 100 mg once daily (95% CI 0.07, 0.62; p = 0.013). CONCLUSION: After adjusting for baseline differences among trials of vildagliptin and sitagliptin in Japanese patients with type 2 diabetes, vildagliptin 50 mg twice daily was associated with significantly greater HbA(1c) reduction than sitagliptin 50 mg or 100 mg once daily.