Real-World Treatment of Patients Newly Diagnosed with Chronic Obstructive Pulmonary Disease: A Retrospective German Claims Data Analysis.

Purpose: This study aimed to describe the real-world treatment of German incident COPD patients, compare that treatment with clinical guidelines, and provide insight into disease development after incident diagnosis. In addition, the economic burden of the disease by assessing COPD-related healthcare costs was described. Patients and Methods: Based on a German claims dataset, continuously insured individuals (04/2014-03/2019) aged 40 years or older with at least two incident pulmonologist's diagnoses or one inpatient diagnosis of COPD (ICD-10-GM code J44.-; no respective diagnosis in a 12-month baseline period) were selected. Treatment patterns after incident diagnosis considering inhaled maintenance therapies identified by ATC codes (outpatient prescriptions) were analyzed. Prescription patterns were compared with recommendations of German COPD treatment guidelines. Severe exacerbations were assessed as hospitalizations with main diagnosis ICD-10-GM code J44.1. COPD-associated costs from the perspective of the health insurance fund AOK PLUS were calculated per patient-year (PY). Results: The sample comprised 17,464 incident COPD patients with a mean age of 71.5 years. 58.9% were male and the mean Charlson-Comorbidity-Index was 5.3. During follow-up (median: 2.0 years), 57.1% of the patients received at least one prescription of an inhaled maintenance therapy, whereas 42.9% did not. Among treated patients, 35.2% started their treatment with LABA/LAMA, 25.3% with LAMA monotherapy, 16.2% with LABA/ICS, and 7.8% with LABA/LAMA/ICS therapy. Within four weeks after initial diagnosis, ICS-containing therapies were prescribed in 14.1% of patients. Of all patients with a prescribed triple therapy, 68.9% had no corresponding exacerbation history documented. On average, 0.16 severe exacerbations and 0.19 COPD-related hospitalizations were observed per PY during available follow-up. Direct COPD-related costs were 3,693 €/PY, with COPD-related hospitalizations being responsible for about 79.2% of these costs. Conclusion: Long-acting bronchodilators are the mainstay of pharmacological treatment of incident COPD patients in Germany, in line with guideline recommendations. Yet, a considerable proportion of incident COPD patients did not receive any inhaled maintenance therapy.

A Non-Interventional Study of Tiotropium/Olodaterol versus Any Triple Combination Therapy for Chronic Obstructive Pulmonary Disease: The EVELUT® Study Protocol.

Background: The Global Initiative for Chronic Obstructive Lung Disease 2020 report recommends that patients with chronic obstructive pulmonary disease (COPD) suffering from persistent dyspnea, despite long-acting ß2-agonist (LABA)/inhaled corticosteroid (ICS) maintenance therapy, are switched to either a long-acting muscarinic antagonist (LAMA)/LABA combination regimen or LAMA/LABA/ICS triple therapy. However, to date, no studies have investigated the direct switch from LABA/ICS to LAMA/LABA therapy-instead of switching to triple therapy-in a prospective, real-world, non-interventional setting. Methods: EVELUT® (NCT03954132) is an ongoing, prospective, open-label, multicenter, non-interventional study comparing the once-daily fixed-dose combination of tiotropium and olodaterol (tio/olo) versus any triple therapy (LAMA/LABA/ICS) in patients with COPD who are symptomatic despite LABA/ICS maintenance therapy. Patients with acute or frequent COPD exacerbations are excluded from the study. Participants will receive LABA/ICS maintenance treatment until Visit 1, followed by switching of treatment to tio/olo or LAMA/LABA/ICS. The primary endpoints are changes in modified Medical Research Council (mMRC) and COPD Assessment Test (CAT®) scores after approximately 12 weeks of treatment. Secondary endpoints are change in the patients' general condition according to the Physician's Global Evaluation score, the proportion of responders with a change in mMRC score of ≥1 and in CAT® score of ≥2, and patient satisfaction with the inhaler and therapy. The study is expected to enroll approximately 900 patients. Conclusion: EVELUT results are expected to add to the current real-world evidence informing therapeutic decisions for COPD in everyday clinical practice. Trial Registration: The European Union electronic Register of Post-authorisation Studies (EU PAS Register): EUPAS29784; the Federal Institute for Drugs and Medical Devices (BfArM): NIS Study No 7305; Clinicaltrials.gov: NCT03954132.

Assessment of physical functioning and handling of tiotropium/olodaterol Respimat® in patients with COPD in a real-world clinical setting.

Background: Patients with chronic obstructive pulmonary disease (COPD) show signs of reduced physical activity from the early stages of the disease, impacting morbidity and mortality. Data suggest treatment with tiotropium, a long-acting muscarinic antagonist, and olodaterol, a long-acting ß2-agonist (LABA), as monotherapies and in combination, increases exercise capacity. This study assessed the effects of fixed-dose tiotropium/olodaterol (delivered via Respimat®) on physical function in Global Initiative for Chronic Obstructive Lung Disease A-D patients requiring long-acting dual bronchodilation treatment in a real-world setting. Methods: This open-label, single arm, noninterventional study measured changes in physical function in COPD patients treated with tiotropium/olodaterol 5/5 µg for approximately 6 weeks (between Visit 1 [baseline] and Visit 2). Primary end point was therapeutic success, defined as a minimum 10-point increase in Physical Functioning Questionnaire (PF-10) score. Secondary end points included change in PF-10 from Visit 1 to Visit 2, the patient's general condition (measured by Physician's Global Evaluation score) at Visit 1 and Visit 2, and patient satisfaction with treatment delivered via the Respimat® device (assessed by Patient Satisfaction Questionnaire) at study end. Results: Therapeutic success was observed in 51.5% of 1578 patients (95% confidence interval [CI] 49.0, 54.0) after approximately 6 weeks of treatment with tiotropium/olodaterol. Mean change in PF-10 score between Visit 1 and Visit 2 was 11.6 points (95% CI 10.7, 12.6). Patient general condition improved as indicated by a general improvement in scores between visits. Most patients were very satisfied or satisfied with tiotropium/olodaterol treatment (82.5%), inhalation (87.5%), and handling of Respimat® (85.2%). One percent of patients reported an investigator-defined drug-related adverse events (AE). Conclusion: Tiotropium/olodaterol treatment improved physical functioning in COPD patients. An associated increase in patient general condition was observed. Most patients were very satisfied or satisfied with tiotropium/olodaterol treatment, inhaling, and handling of the Respimat® device. No unexpected drug-related AE occurred.

Asthma control in patients treated with inhaled corticosteroids and long-acting beta agonists: A population-based analysis in Germany.

BACKGROUND: The prevalence and the characteristics of poor asthma control among adults treated with combinations of inhaled corticosteroids (ICS) and long-acting beta-agonists (LABA) are not completely understood. METHODS: Data from adult patients in Germany with self-reported asthma treated with an ICS-LABA combination in the National Health and Wellness Survey (NHWS) were analysed. Patients with well-controlled and not well-controlled asthma according to the Asthma Control Test (ACT) score were compared, with respect to socio-demographic characteristics, attitudes, adherence and outcomes. RESULTS: Among the German patients with self-reported asthma (5.2% of the respondents), 16.2% (382 patients) were treated with an ICS-LABA combination and did not report concomitant chronic obstructive pulmonary disease, chronic bronchitis or emphysema. In this subgroup, 55.8% had not well-controlled asthma (ACT < 20). ICS-LABA treated patients with not well-controlled asthma were more likely to report emergency visits (16.4% vs. 8.9%), missed more time from work (absenteeism: 12.9% vs. 4.3%), were more impaired while at work (presenteeism: 29.0% vs. 14.9%) and were more likely to be women (69.0% vs. 57.4%), compared with well-controlled patients. There were no significant differences in age, body mass index, smoking, income, education or self-reported adherence between the two groups, but different attitudes regarding the patient-physician relationship. CONCLUSIONS: A substantial proportion of patients treated with ICS and LABA had not well-controlled asthma. These patients did not differ from well-controlled patients in terms of education or self-reported adherence, but in terms of their attitudes regarding the patient-physician relationship.

Ribozyme to TGF-beta1 mRNA abrogates immunosuppressive effects of human colorectal adenocarcinoma HRT-18 cells in vitro and in vivo.

Transforming growth factor-beta1 (TGF-beta1) is overexpressed in a variety of malignant epithelial tumors and was suggested to be a marker of colorectal cancer. Moreover, there is growing evidence that TGF-beta1 contributes to tumor progression by regulating tumor cell proliferation and differentiation, inducing a favorable tumor microenvironment, promoting migration and invasion, and suppressing macrophage cytotoxicity. Therefore, we stably transfected an anti-TGF-beta1 hammerhead ribozyme into the human colorectal adenocarcinoma cell line HRT-18. Expression of this ribozyme resulted in significant inhibition of TGF-beta1 expression on mRNA and protein level. This was associated with an enhanced tumor cell differentiation and a reduced tumor growth in vivo. The capability of tumor cells to suppress ROI production of co-cultivated human macrophages was abrogated in transfectants. Taken together, inhibition of TGF-beta1 in colorectal carcinoma cells might be an interesting therapeutic tool leading to reduced tumor cell growth and increased macrophage cytotoxicity. Thus, a gene-therapeutic approach using anti-TGF-beta1 ribozyme in combination with established anti-tumor agents is of great promise.