Joanna Diesing

Purpose: This study describes the pharmacological treatment as well as the clinical and economic burden of disease in chronic obstructive pulmonary disease (COPD) patients initiating triple therapy (TT) defined as a combination of a long-acting muscarinic antagonist (LAMA), a long-acting beta2-agonist (LABA) and an inhaled corticosteroid (ICS) in Germany. Patients and Methods: All COPD patients aged 40 years and older in an anonymized claims database who initiated TT in 2017 were included. Adherence to TT and the use of the guideline-recommended escalation therapies were measured during two years of follow-up. We also describe the number of exacerbations, healthcare resource utilization, and direct healthcare costs observed during the follow-up. Results are reported for the total study population and a subgroup adherent to TT. Results: Of the 3,458,989 insured individuals in 2017, 6,532 initiated TT. Cardiovascular, respiratory, metabolic, and psychiatric comorbidities were common. Only one in six patients was adherent to TT over two years and one third experienced exacerbations; 18% had one exacerbation, 7% had two, 3% had three and 5% had four or more exacerbations during the follow-up. Both COPD-related and all-cause healthcare costs increased with the number of exacerbations during follow-up, as did the proportion of COPD-related costs among all healthcare costs. Mean all-cause costs per person-year of follow-up were € 8,110 for patients without and € 20,832 for patients with four or more exacerbations, respectively. Escalation therapy with roflumilast, which is recommended in German guidelines, was prescribed to 3.1% of patients, of whom two-thirds discontinued the drug during the two-year follow-up. Conclusion: A substantial proportion of COPD patients initiating TT experience exacerbations resulting in high resource utilization and costs for the healthcare system. With poor treatment adherence and rare use of guideline-recommended escalation therapies, effective new treatments are needed to address the unmet medical need in this patient population.

Purpose: Patients with COPD suffer from various comorbidities, seemingly leading to a collective increase in morbidity and mortality. However, comorbidities with COPD have been largely unreported. Patients and Methods: Using healthcare claims data, only the deceased among around 250,000 COPD patients diagnosed in 2011– 2018 were evaluated by cause of death (cumulative incidence without competing risk) across a period of up to eight years. Results were compared with 1:1 propensity score-matched controls. Additionally, the prevalence of comorbidities in deceased patients was compared. Results: On average, deceased COPD patients and matched controls lived to be 75.7 and 78.0 years, respectively, and COPD patients had more comorbidities prior to death (mean 4.53 and 3.65). Both respiratory and cardiovascular-related deaths were more likely in COPD patients than in their matched controls (3.3 and 1.6 percentage points higher after eight years), and this was more extreme (9.8 and 3.4 percentage points higher, respectively) in the COPD subgroup with multiple/severe exacerbations; cumulative incidence of death increased with increasing COPD severity. Comorbidity prevalence, especially cardiovascular-related, was higher in COPD patients than in matched controls; COPD patients had a 42% higher risk of heart failure (RR 1.42; 1.38– 1.47), 30% higher risk of ischemic heart disease (RR 1.30; 1.25– 1.35), and 27% increased risk of atrial fibrillation (RR 1.27; 1.21– 1.32). Conclusion: In this real-world observational retrospective cohort study, we found patients with COPD died at a younger age, and developed more comorbidities, than matched controls. Plain Language Summary: People affected by COPD have other health issues. We studied a cohort of deceased insurees, comparing the health status of those with, to those without COPD, before death. The database had data from 250,000 COPD patients, over a period of up to eight years. More people with COPD died from respiratory or heart-related causes. They also died younger and had more additional health issues, compared to the non-COPD cohort, regardless of cause of death. The COPD cohort had higher rates of asthma, pneumonia, various heart conditions, dementia, depression, cancer, and osteoporosis, compared to the non-COPD cohort; they were more likely to have these comorbidities diagnosed particularly before death. For example, the risk of pneumonia, atrial fibrillation, and heart failure was up to 83% higher in the COPD cohort. The risk of depression was also 78% higher in those with COPD than in the cohort without COPD. This information shows a clear link between COPD and other health issues, especially those related to the lungs and heart. Treatment guidelines for COPD patients should target multiple health issues at once.

(1) Background: Achieving inactive disease decreases long-term joint damage in patients with polyarticular juvenile idiopathic arthritis (polyJIA). The aim of our study was to describe average time to treatment and medication changes over time. (2) Methods: Incident polyJIA patients were retrospectively identified in the InGef and WIG2 longitudinal health claims databases. Drug escalation level changes were evaluated longitudinally and cross-sectionally across three years, as follows: no treatment, glucocorticoids (GCs) and/or non-steroidal anti-inflammatory drugs (NSAIDs), conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), and biological disease-modifying antirheumatic drugs (bDMARDs). (3) Results: On average, newly diagnosed polyJIA patients received their first csDMARD prescription after 128 days and their first bDMARD prescription after 327 days. More patients were treated with csDMARDs than with bDMARDs at diagnosis; however, 24% and 12% (InGef and WIG2 databases, respectively) had no JIA treatment. After three years, 45% and 31% were not taking any treatments, while 18% and 36% were prescribed bDMARDs. Among patients initiating bDMARDs, most continued treatment for three years, with some switching to csDMARDs or discontinuing treatment. Patients treated only with csDMARDs took them longer, compared to those additionally taking other DMARDs. Patients treated with bDMARDs took them about twice as long as the csDMARDs they took prior. (4) Conclusion: A substantial number of patients with polyJIA are not treated as intensively as guidelines recommend.

Background Treatment of polyarticular juvenile idiopathic arthritis (polyJIA) aims to ease symptoms and inflammation and reduce further damage and comorbidities[1]. Current treatment options however are not universally effective. With the first targeted synthetic disease modifying anti-rheumatic agent having recently been approved information on how many polyJIA patients may potentially benefit from newly accessible treatment options is needed. Objectives Describe current treatment patterns around incident polyJIA diagnosis and beyond, especially changes in medication regimes indicative of unsatisfactory response. Methods In a retrospective, observational analysis of two different non-overlapping longitudinal health claims databases (the WIG2, Scientific Institute for Health Economics and Health System Research GmbH, and InGef, Institute for Applied Health Research Berlin GmbH, databases), a representative sample in terms of age and gender of the statutory health insurance (SHI) population in Germany (about 3.5 and 4 million patients, respectively) was analysed. Two incident JIA cohorts were evaluated (2014 and 2015) in each databank, and followed up for 4 or 3 years, respectively. All incident JIA patients (without a JIA diagnosis during baseline, the 4 quarters prior to index) aged 2 to 15 years in the respective observation year (2014 and 2015), with continuous data throughout the observation year and minimum 3-year follow-up (or deceased) were included. Patients were considered to have polyJIA if they had at least one inpatient ICD-10 GM (German modification) diagnosis code, or two verified outpatient codes in two different quarters in the year, of M08.0 (juvenile chronic polyarthritis, adult type, includes rheumatoid factor (RF)+ polyJIA), or M08.3 (juvenile chronic arthritis (seronegative), polyarticular form, includes RF- polyJIA and extended oligoarthritis). We evaluated top-prescribed and pre-defined medications (by 4-digit ATC code) before, during, and following, incident polyJIA diagnosis. The pre-defined medication groups were non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids (GCs), conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs), and biologic disease modifying anti-rheumatic drugs (bDMARDs). Results Applying the inclusion and exclusion criteria to the incident JIA populations, we identified a total of 121 and 58 polyJIA patients in both 2014 and 2015, (of which 56 and 29 belonged to the 2015 cohort) in the InGef and WIG2 databases, respectively. Among the most frequently prescribed drugs were anti-inflammatory and anti-rheumatic drugs, specific anti-rheumatic agents, and nasal decongestants, immunosuppressive agents, vitamin B12 and folic acid. Prior to diagnosis, more than half of patients of the 2015 cohort were already receiving NSAIDs, however at diagnosis the use of csDMARDs increased more than bDMARD use. From diagnosis quarter to follow-up, there was a proportionally larger increase in the use of bDMARDs than csDMARDs, however use of all medications we examined (also NSAIDs and GCs) in our population continued to increase through follow-up (fig 1). Treatment patterns were similar for both cohorts (2014 and 2015). Conclusion Almost all patients continued to take NSAIDs during follow-up, many had concomitant medication with glucocorticoids in addition to csDMARDs or bDMARDs. This demonstrates there was an unmet need in the past for further advanced treatment options such as targeted synthetic DMARDs. Reference [1] Oommen, Prasad Thomas. 027-020l_S2k_Juvenile_Idiopathische_Arthritis_2020-10. Accessed December 17, 2021. https://www.awmf.org/uploads/tx_szleitlinien/027-020l_S2k_Juvenile_Idiopathische_Arthritis_2020-10.pdf Pre-defined medications for patients with incident polyJIA in the 2015 cohort, for baseline (prior to year of diagnosis), index (diagnosis year) and follow-up (up to 3 years after diagnosis), *indicates nAcknowledgements: NIL. Disclosure of Interests Gerd Horneff Speakers bureau: Pfizer, Novartis, Sobi, Consultant of: MSD, Lilly, Grant/research support from: Novartis, MSD, Roche, Julia Borchert Consultant of: Julia Borchert is an employee of WIG2 GmbH, which is an independent institute and paid consultant to Pfizer Pharma GmbH for designing the study, carrying out the analyses, interpreting the results and writing the , Grant/research support from: Julia Borchert is an employee of WIG2 GmbH, which is an independent institute and paid consultant to Pfizer Pharma GmbH for designing the study, carrying out the analyses, interpreting the results and writing the , Joanna Diesing Consultant of: Joanna Diesing is an employee of WIG2 GmbH, which is an independent institute and paid consultant to Pfizer Pharma GmbH for designing the study, carrying out the analyses, interpreting the results and writing the , Grant/research support from: Joanna Diesing is an employee of WIG2 GmbH, which is an independent institute and paid consultant to Pfizer Pharma GmbH for designing the study, carrying out the analyses, interpreting the results and writing the , Pascal Klaus Employee of: Pascal Klaus in an employee of Pfizer Pharma GmbH., Ria Heinrich Consultant of: Ria Heinrich is an employee of WIG2 GmbH, which is an independent institute and paid consultant to Pfizer Pharma GmbH for designing the study, carrying out the analyses, interpreting the results and writing the , Grant/research support from: Ria Heinrich is an employee of WIG2 GmbH, which is an independent institute and paid consultant to Pfizer Pharma GmbH for designing the study, carrying out the analyses, interpreting the results and writing the , Heike Dally Employee of: Heike Dally in an employee of Pfizer Pharma GmbH., Christine Hagemann Employee of: Christine Hagemann in an employee of Pfizer Pharma GmbH., Simon Kock: None declared, Tonio Schoenfelder Consultant of: Tonio Schoenfelder is an employee of WIG2 GmbH, which is an independent institute and paid consultant to Pfizer Pharma GmbH for designing the study, carrying out the analyses, interpreting the results and writing the , Grant/research support from: Tonio Schoenfelder is an employee of WIG2 GmbH, which is an independent institute and paid consultant to Pfizer Pharma GmbH for designing the study, carrying out the analyses, interpreting the results and writing the

Aims: This study evaluates type 2 diabetes mellitus (T2DM) prevalence in Germany, focusing on patients at risk for, or with already established, cardiovascular disease (CVD), as well as their antidiabetic and cardiovascular treatments. Materials and Methods: Using anonymized claims data from the WIG2 database, we calculated 2018 T2DM prevalence, extrapolating rates to the German statutory health insurance population. In the study period, 3 376 228 patients were eligible in the database. Forming antidiabetic medication groups, we evaluated treatment regimens of patients at risk for, or with already established CVD, based on the REWIND study criteria. We also evaluated their CVD medication prescriptions. Results: Statutory health insurance extrapolated T2DM prevalence was estimated at 11.9%, with higher prevalence rates in older patients. When only patients with prescriptions of antidiabetic drugs were included, prevalence was 7.6%. At least 94% of patients with T2DM medication had at least one risk factor (without considering age) according to REWIND criteria, while 67%‐80% had at least two risk factors depending on treatment received. Patients taking insulin combined with oral therapy comprised the largest proportion of patients with at least two REWIND risk factors. Approximately 85% of all patients with T2DM in the population were treated with antihypertensive medication. Conclusions: T2DM is widespread and affects older patients particularly. Most patients with T2DM had at least one CV risk factor, and about half already had established CVD. Early prevention of CVD, which disproportionately affects patients with T2DM, is necessary. Furthermore, the treatment of older patients with T2DM with insulin is still common and needs further evaluation.

Background: COPD exacerbations may result in increased morbidity and mortality. Recent studies using models to evaluate the predictive value of different variables on future exacerbations, suggest that exacerbation history is the strongest predictor. We examined the effect of exacerbation history on subsequent exacerbations in a large sample population with over 250,000 real-world COPD patients, using up to 8 years of longitudinal healthcare data from Germany. Methods and Results: Healthcare insurance claims (Germany; WIG2 research database) were obtained 2011 – 2017 as the index period with 12 months before and after for baseline assessment and follow-up. Patients 40 years or older with any COPD diagnosis in primary or secondary care within the study time frame (January 1st, 2011 to December 31st, 2017) were included. Baseline exacerbations 12 months pre-index were defined as moderate (treatment with oral corticosteroids or antibiotics, J01AA, J01CA) or severe (emergency visit or hospitalization). Exacerbation risk by baseline exacerbation number and severity was estimated as cumulative incidence with 95% CIs adjusted for death. A total of 250,723 COPD patients (mean age 63.0 years, 43% women) were included. On average, patients with one moderate baseline exacerbation experienced 1.9 (1.9 – 1.9) exacerbations during the first 3 years of follow-up, whereas patients with either one severe baseline exacerbation, or 2 or more moderate and/or severe baseline exacerbations experienced 6.3 (6.1 – 6.3) exacerbations. More than half of patients with a moderate baseline exacerbation developed another event within 3 years, more than a third of patients without baseline exacerbations experienced at least one exacerbation during the same time frame. Conclusion: Patients with a severe or multiple baseline exacerbation history had a markedly higher risk for and shorter time to a subsequent exacerbation. Having had one moderate baseline exacerbation increased the risk of a subsequent exacerbation throughout follow-up. The present data highlights a need for strategies regarding management and treatment of COPD patients to prevent subsequent exacerbations. Article published online: 30 April 2021 © 2021. Thieme. All rights reserved. Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany