Publikationen

Hardtstock F, Foskett N, Gille P, Joeres L, Molzan M, Wilson J, Wilke T, Holtkamp M. Poststroke epilepsy incidence, risk factors and treatment: German claims analysis. Acta Neurol Scand. 2021 Jun;143(6):614-623.

Abstract

Objectives:

To describe incidence, risk factors, and treatment of poststroke epilepsy (PSE) in Germany based on claims data.

Methods:

Retrospective analysis of claims data from a German public sickness fund (AOK PLUS). Patients with acute stroke hospitalizations from January 01, 2011 and December 31, 2015 (index hospitalization) were followed for 12-72 months. Outcomes included incidence of PSE (patients with ≥2 seizure claims [during/after index hospitalization], or ≥1 seizure claim after index hospitalization), multivariate Cox-regression analyses of time to seizure claim and death after index stroke hospitalization discharge, and antiepileptic drug (AED) treatment.

Results:

Among 53 883 patients with stroke (mean follow-up of 829.05 days [median 749]), 6054 (11.24%) had ≥1 seizure claim (mean age 73.95 years, 54.18% female). 2130 (35.18%) patients had a seizure claim during index hospitalization (indicative of acute symptomatic seizures). Estimated incidence of PSE (cases/1000 patient-years) was 94.49 within 1 year. Risk of seizure claim following hospital discharge was higher in patients with hemorrhagic stroke (hazard ratio [HR] =1.13; p <.001) vs those with cerebral infarction. Seizure claim during index hospitalization was a risk factor for seizure claims after hospital discharge (HR =6.97; p <.001) and early death (HR =1.78; p <.001). In the first year of follow-up, AEDs were prescribed in 73.75% of patients with seizure claims.

Conclusions:

Incidence of PSE was in line with previous studies. Hemorrhagic stroke and seizure claim during index hospitalization were risk factors for seizure claims after hospital discharge. Most patients with seizure claims received AED treatment.

Mueller S, Junker S, Wilke T, Lommatzsch A, Schuster A, Kaymak H, Ehlken C, Ziemssen F. Questionnaire for the assessment of adherence barriers of intravitreal therapy: the ABQ-IVT. Int J Retina Vitreous. 2021 Jun 2;7(1):43.

Abstract

Objective:

To develop and validate a questionnaire for the investigation of non-adherence (NA) barriers in patients receiving intravitreal injection (IVT).

Design:

Questionnaire development and cross-sectional patient survey combined with a retrospective medical chart review.

Participants:

German patients with neovascular age-related macular degeneration (nAMD) or diabetic macular edema (DME) receiving anti-vascular endothelial growth factor (anti-VEGF) treatment via IVT.

Methods:

The previously validated (indications: atrial fibrillation, human immunodeficiency virus, chronic inflammatory lung disease) Adherence Barriers Questionnaire (ABQ) was revised according to specifications of IVT, within the framework of an expert panel. The ABQ-IVT, which initially consisted of 24 items formulated as statements (4-point-Likert-scale ranging from "strongly agree" to "strongly disagree"), was applied in a cross-sectional survey. Evaluation of the questionnaire included an assessment of internal consistency and factor analysis. The occurrence of potential barriers in the patient sample was evaluated using descriptive statistics. To identify patient subpopulations, hierarchical cluster analysis was performed using ABQ-IVT answers as predictors. Due to difficulties in capturing NA as an external criterion, the evaluation of the questionnaire was limited to its internal validity and reliability.

Main outcome measures:

Patients' answers to the ABQ-IVT questionnaire and interviews.

Results:

Of 253 patients, 234 (92%) were able to complete the ABQ-IVT questionnaire. Within the reliability analysis, the ABQ-IVT was reduced to 17 items. The condensed questionnaire demonstrated good internal consistency (Cronbach's alpha = 0.78), and factor analysis showed no evidence for subscales of the questionnaire. Nearly half of the patients (49%) reported being affected by at least three different barriers. On average, a patient was affected by 3.1 barriers. The most frequently reported barriers were "Challenge due to time commitment of physician visits" (45% of the patients), "Depression" (29%) and "Travel and opportunity costs" (27%). Cluster analysis identified six patient subpopulations, each affected by different sets of barriers and differed regarding their patient characteristics.

Conclusions:

The ABQ-IVT is a practical and reliable instrument for identifying patient-specific barriers to IVT treatment adherence. In practice, the questionnaire may be useful in assessing whether individual patients are at higher risk of NA due to specific adherence barriers. Aside from better awareness, this allows earlier interventions, though these still need to be validated. Patient subpopulations face different barriers and may, therefore, need distinct preventative care.

Mueller S, Maywald U, Timmermann H, Unmüßig V, Welte R, Hardtstock F, Wilke T. Identifying the Causes Increasing the Risk of Non-Adherence in Adult Patients with Asthma: An Analysis Combining Patient Survey Data with German Claims Data. Drugs Real World Outcomes. 2021 Jun;8(2):207-214.

Abstract

Background:

There exists a range of treatments in the management of asthma. Non-adherence to these medications has been identified as a factor negatively impacting the effects of treatment.

Objective:

The objective of this study was to identify the potential barriers to medication adherence among adult patients with asthma in Germany.

Patients and methods:

A multi-center observational study was conducted addressing adult patients with asthma who were prescribed regular maintenance medication between 2014 and 2016. Data were derived from physicians' documentation as well as claims data, which were linked to the above primary observational data, and patient survey data. Adherence barriers were assessed by the validated Adherence Barriers Questionnaire, both descriptively and in a logistic regression framework. Cluster analysis identified distinct patient groups with respect to the relevance of specific adherence barriers.

Results:

We included 524 patients with asthma (mean age 53.1 years, 74.6% female, 43.1% allergic asthma, 37.6% nonallergic, 19.3% mixed). Most of the participants reported to face at least three barriers (61.1%). Frequently reported barriers were the perception that medications are all harmful (53.6% of the participants), the burden of medication co-payment (44.1%), positive perception about current health status (39.9%), feeling of depression (30.9%), and the fear of side effects (27.5%). Four distinct patient clusters could be identified: cluster 1 with a low number of barriers (28.6% of participants), cluster 2 (11.6%) with a comparably high number of existing barriers, cluster 3 with high importance of depression as a barrier (27.3% of participants), and cluster 4 that was dominated by the perception that medications are all harmful (32.5% of participants).

Conclusions:

Results of this study provide important insights for further development of adherence programs, which should focus on distinct patients' clusters that differ substantially in the relevance of specific adherence barriers.

Hardtstock F, Kocaata Z, Wilke T, Dittmar A, Ghiani M, Belozeroff V, Harrison D, Maywald U, Tesch H. Healthcare resource utilization and associated cost of patients with bone metastases from solid tumors who are naïve to bone-targeting agents: a comparative analysis of patients with and without skeletal-related events. Eur J Health Econ. 2021 Mar;22(2):243-254.

Abstract

Background:

This study analyzes the impact of skeletal-related events (SRE) on healthcare resource utilization (HCRU) and costs incurred by patients with bone metastases (BM) from solid tumors (ST), who are therapy-naïve to bone targeting agents (BTAs).

Methods:

German claims data from 01/01/2010 to 30/06/2018 were used to conduct a retrospective comparative cohort analysis of BTA-naive patients with a BM diagnosis and preceding ST diagnosis. HCRU and treatment-related costs were compared in two matched cohorts of patients with and without a history of SREs, defined as pathological fracture, spinal cord compression, surgery to bone and radiation to bone. The first SRE was defined as the patient-individual index date. Conversely, for the non-SRE patients, index dates were assigned randomly.

Results:

In total, 45.20% of 9,832 patients reported experiencing at least one SRE (n = 4444) while 54.80% experienced none (n = 5388); 2,434 pairs of SRE and non-SRE patients were finally matched (mean age: 70.87/71.07 years; females: 39.07%/38.58%). Between SRE and non-SRE cohorts, significant differences in the average number of hospitalization days per patient-year (35.80/30.80) and associated inpatient-care costs (14,199.27€/10,787.31€) were observed. The total cost ratio was 1.16 (p < 0.001) with an average cost breakdown of 23,689.54€ and 20,403.27€ per patient-year in SRE and non-SRE patients.

Conclusion:

The underutilization of BTAs within a clinical setting poses an ongoing challenge in the real-world treatment of BM patients throughout Germany. Ultimately, the economic burden of treating SREs in patients with BM from ST was found to be considerable, resulting in higher direct healthcare costs and increased utilization of inpatient care facilities.

Wilke T, Mueller S, Fuchs A, Kaltoft M, Kipper S, Cel M. Diabetes-Related Effectiveness and Cost of Liraglutide or Insulin in German Patients with Type 2 Diabetes: A 5-Year Retrospective Claims Analysis. Diabetes Ther. 2020 Oct;11(10):2357-2370.

Abstract

Introduction:

Liraglutide is a glucagon-like peptide-1 analogue used to treat type 2 diabetes mellitus (T2DM). To date, limited long-term data (> 2 years) exist comparing real-world diabetes-related effectiveness and costs for liraglutide versus insulin treatment.

Methods:

This retrospective claims data analysis covered the period from 1 January 2010 to 31 December 2017 and included continuously insured patients with T2DM who initiated insulin or liraglutide and had 3.5 or 5 years' follow-up data, identified using the German AOK PLUS dataset. Propensity score matching (PSM) was used to adjust for patient characteristics.

Results:

After PSM, there were 825 and 436 patients in the liraglutide and insulin groups at 3.5 and 5 years' follow-up, respectively. Baseline characteristics were similar between compared cohorts. The respective change from baseline to follow-up in mean glycated haemoglobin for liraglutide and insulin patients was - 0.88% and - 0.81% (p > 0.100) after 3.5 years and - 1.15%/ - 1.02% (p > 0.100) after 5 years. Mean respective changes in body mass index (kg/m²) were - 1.21/+ 1.14 (p < 0.001) after 3.5 years and - 1.29/+ 1.13 after 5 years (p < 0.001). Liraglutide- versus insulin-treated patients were less likely to have an early T2DM-related hospitalisation (3.5-year hazard ratio [HR]: 0.414 [95% confidence interval (CI) 0.263-0.651]; 5-year HR: 0.448 [95% CI 0.286-0.701]). At 5 years' follow-up, there was no statistically significant difference in total direct costs between treatment groups (cost ratio: 1.069 [95% CI 0.98-1.13]; p > 0.100).

Conclusion:

The clinical effectiveness of liraglutide is maintained long term (up to 5 years). Liraglutide treatment is not associated with higher total direct healthcare costs.

Bokemeyer B, Ghiani M, Fuchs A, Deiters B, Hardtstock F, Brandes A, Knop J, Orzechowski H, Wilke T. Indicators of active disease and steroid dependency in patients with inflammatory bowel diseases not treated with biologics in a German real-world-setting. Int J Colorectal Dis. 2020 Aug;35(8):1587-1598.

Abstract

Background and aims:

While a minority of inflammatory bowel disease (IBD) patients receives biologics in Germany, little is known about therapeutic needs of patients receiving non-biologic therapies. This study aimed to identify indicators of active disease/steroid dependency in patients with moderate to severe Crohn's disease (CD) and ulcerative colitis (UC) treated with conventional therapies and to describe health care resource use (HCRU)/cost.

Methods:

CD/UC patients treated with immunosuppressants (IS) and/or systemic or locally acting oral corticosteroids (CS) were identified in German claims data (2013-2017) and followed for 12 months post-therapy start. Indicators of active disease/steroid dependency during follow-up period were (i) ≥ 2 prescriptions of CS (sensitivity ≥ 4) or (ii) ≥ 1 IBD-related surgery or (iii) > 7 days IBD-related hospitalization(s).

Results:

Of 9871 included IBD patients (5170 CD, 4701 UC), 25.7%/19.9% (CD/UC) received ≥ 2 prescriptions of CS (sensitivity, 17.4%/15.7%) (i), 3.2% experienced IBD-related surgeries (ii), and 2.5% > 7 days of hospitalizations (iii). Altogether, 44.4% had indicators of active disease/steroid dependency (sensitivity, 23.9%). Among patients with active disease/steroid dependency, 78.0% received CS monotherapy at baseline. Of these, 89.6% received a CS monotherapy in the follow-up period, too. Proportionally, fewer patients with CS monotherapy (57.4%) than IS therapy (91.0%) visited a specialist. HCRU/cost per patient year was significantly higher in patients with than without active disease/steroid dependency.

Conclusions:

A substantial percentage of biologic-naïve IBD patients suffers from active disease/steroid dependency. The majority receives a monotherapy with systemic CS. Referral to gastroenterologists for treatment optimization is recommended, also because active disease/steroid dependency is associated with increased HCRU/cost.

Hadji P, Hardtstock F, Wilke T, Joeres L, Toth E, Mockel L, Gille P. Estimated epidemiology of osteoporosis diagnoses and osteoporosis-related high fracture risk in Germany: a German claims data analysis. Arch Osteoporos. 2020 Aug 12;15(1):127.

Abstract

Summary
In 2016, an estimated 143,967 female and 25,315 male patients had a diagnosis of osteoporosis, accounting for 4.44% of the German population. Due to an aging population, an increase in the number of osteoporosis patients and osteoporotic fractures can be expected, posing a substantial burden on healthcare systems.

Purpose
Osteoporosis is one of the most prevalent diseases in developed countries, mainly affecting older adults. It leads to decreased bone mass, bone microarchitecture deterioration, and increased risk of fracture. This epidemiological study investigated the prevalence and incidence of osteoporosis diagnoses and assessed the number of osteoporosis patients who are at high risk of vertebral/femoral fracture.

Methods
We analyzed German claims data (AOK PLUS) covering 2010–2016. All included patients were diagnosed with osteoporosis (ICD-10 M80.*/M81.*). Vertebral/femoral and other fractures were identified based on respective ICD-10 codes. Patient numbers were extrapolated to the entire German population, based on patient age and gender.

Results
In 2016, 169,282 patients (143,967 females and 25,315 males) had prevalent osteoporosis, 25,996 (20,425 females and 5571 males) of which were newly diagnosed that year. Extrapolated prevalence for Germany was 3.61 million patients (4.44% of the German population). Extrapolated incidence was 0.62 million patients. Of patients with prevalent osteoporosis, 13,613 experienced an incident vertebral/femoral fracture in 2016 (German extrapolation: 258,957 patients). Of these, 36.88% received an osteoporosis treatment that year.

Conclusion
Our study identified a high number of prevalent and incident patients with osteoporosis claims in Germany. The increasing age of the German population will likely lead to a significant increase in the number of patients with osteoporosis over the next decades. Treatment of osteoporosis patients with high fracture risk, especially those with a recent vertebral/femoral fracture, should be of particular focus, as a substantial proportion does not receive a guideline-based treatment.

Mueller S, Heidler T, Fuchs A, Pfaff A, Ernst K, Ladinek G, Wilke T. Real-World Treatment of Patients with Multiple Sclerosis per MS Subtype and Associated Healthcare Resource Use: An Analysis Based on 13,333 Patients in Germany. Neurol Ther. 2020 Jun;9(1):67-83.

Abstract

Introduction:

The aim of this study was to describe the real-word treatment and associated healthcare resource use (HCRU) of multiple sclerosis (MS) patients, as stratified by different MS subtypes.

Methods:

All patients with MS continuously insured by two German statutory healthcare insurance funds from 2011 to 2015 were enrolled. These patients were categorized into four subgroups according to their MS type as follows: clinically isolated syndrome (CIS); relapsing remittent MS (RRMS); primary progressive MS (PPMS); and secondary progressive MS (SPMS). Sociodemographic characteristics, treatments, and HCRU for 2015 were analyzed. Treatment cascades for treatment-naïve patients were also determined.

Results:

A total of 13,333 patients with MS were identified. The largest proportion of patients had RRMS (41.9%), followed by PPMS (17.1%). Mean age of the enrolled patients was 50.2 years, and 70.7% were female. Among all patients, 38.3% of those with CIS, 22.4% with PPMS, 69.6% with RRMS, and 33.9% with SPMS received a prescription of a disease-modifying immunomodulatory agent, with interferon beta-1a being the most frequently prescribed agent. Likewise, 14.5, 18.5, 19.9, and 21.5% of patients with CIS, PPMS, RRMS, and SPMS, respectively, received a flare-up treatment with glucocorticoids. MS-associated overall costs, including indirect costs for MS-associated days absent from work, were € 16,433, with costs related to MS medication (€ 8770; 53.4%) being the main driver of costs in all subgroups. MS-associated costs according to MS subtypes were € 12,427 for CIS patients, € 14,459 for PPMS patients, € 20,583 for RRMS patients, and € 17,554 for SPMS patients.

Conclusion:

Among the four MS subtypes, RRMS patients most often received a disease-modifying immunomodulatory treatment. Consequently, healthcare costs were highest for patients with this MS subtype. Contrary to the treatment guideline, a substantial percentage of patients with CIS, RRMS, and SPMS did not receive any disease-modifying immunomodulatory treatment.

Hardtstock F, Heinrich K, Wilke T, Mueller S, Yu H. Burden of Staphylococcus aureus infections after orthopedic surgery in Germany. BMC Infect Dis. 2020 Mar 19;20(1):233.

Abstract

Background:

This study assessed incidence, risk factors, and outcomes of Staphylococcus aureus infections (SAI) following endoprosthetic hip or knee, or spine surgeries.

Methods:

Adult patients with at least one of the selected surgeries from 2012 to 2015 captured in a German sickness fund database were included. SAI were identified using S. aureus-specific ICD-10 codes. Patients with certain prior surgeries and infections were excluded. Cumulative incidence and incidence density of post-surgical SAI were assessed. Risk factors, mortality, healthcare resource utilization and direct costs were compared between SAI and non-SAI groups using multivariable analyses over the 1 year follow-up.

Results:

Overall, 74,327 patients who underwent a knee (28.6%), hip (39.6%), or spine surgery (31.8%) were included. The majority were female (61.58%), with a mean age of 69.59 years and a mean Charlson Comorbidity Index (CCI) of 2.3. Overall, 1.92% of observed patients (20.20 SAI per 1000 person-years (PY)) experienced a SAI within 1 year of index hospitalization. Knee surgeries were associated with lower SAI risk compared with hip surgeries (Hazard Ratio (HR) = 0.8; p = 0.024), whereas spine surgeries did not differ significantly from hip surgeries. Compared with non-SAI group, the SAI group had on average 4.4 times the number of hospitalizations (3.1 vs. 0.7) and 7.7 times the number of hospital days (53.5 vs. 6.9) excluding the index hospitalization (p < 0.001). One year post-orthopedic mortality was 22.38% in the SAI and 5.31% in the non-SAI group (p < 0.001). The total medical costs were significantly higher in the SAI group compared to non-SAI group (42,834€ vs. 13,781€; p < 0.001). Adjusting for confounders, the SAI group had nearly 2 times the all-cause direct healthcare costs (exp(b) = 1.9; p < 0.001); and 1.72 times higher risk of death (HR = 1.72; p < 0.001).

Conclusions:

SAI risk after orthopedic surgeries persists and is associated with significant economic burden and risk of mortality. Hence, risk reduction and prevention methods are of utmost importance.

Hardtstock F, Myers D, Li T, Cizova D, Maywald U, Wilke T, Griesinger F. Real-world treatment and survival of patients with advanced non-small cell lung Cancer: a German retrospective data analysis. BMC Cancer. 2020 Mar 30;20(1):260.

Abstract

Background:

The objective of this study was to describe the real-world treatment and overall survival (OS) of German patients with a diagnosis of advanced non-small cell lung cancer (aNSCLC), and to explore factors associated with the real-world mortality risk.

Methods:

This was a retrospective German claims data analysis of incident aNSCLC patients. Data were available from 01/01/2011 until 31/12/2016. Identification of eligible patients took place between 01/01/2012-31/12/2015, to allow for at least 1-year pre-index and follow-up periods. Inpatient and outpatient mutation test procedures after aNSCLC diagnosis were observed. Further, prescribed treatments and OS since first (incident) aNSCLC diagnosis and start of respective treatment lines were described both for all patients and presumed EGFR/ALK/ROS-1-positive patients. Factors associated with OS were analyzed in multivariable Cox regression analysis.

Results:

Overall, 1741 aNSCLC patients were observed (mean age: 66·97 years, female: 29·87%). The mutation test rate within this population was 26·31% (n = 458), 26·6% of these patients (n = 122) received a targeted treatment and were assumed to have a positive EGFR/ALK/ROS-1 test result. Most often prescribed treatments were pemetrexed monotherapy as 1 L (21·23% for all and 11·11% for mutation-positive patients) and erlotinib monotherapy as 2 L (25·83%/38·54%). Median OS since incident diagnosis was 351 days in all and 571 days in mutation-positive patients. In a multivariable Cox regression analysis, higher age, a stage IV disease, a higher number of chronic drugs in the pre-index period and no systemic therapy increased the risk of early death since first aNSCLC diagnosis. On the other hand, female gender and treatment with therapies other than chemotherapy were associated with a lower risk of early death.

Conclusions:

Despite the introduction of new treatments, the real-world survival prognosis for aNSCLC patients remains poor if measured based on an unselected real-world population of patients. Still, the majority of German aNSCLC patients do not receive a mutation test.