Characteristics of Users and New Initiators of Single- and Multiple-Inhaler Triple Therapy for Chronic Obstructive Pulmonary Disease in Germany.

Purpose: To assess patient characteristics of users and new initiators of triple therapy for chronic obstructive pulmonary disease (COPD) in Germany. Patients and Methods: Retrospective cohort study of patients with COPD and ≥1 prescription for single-inhaler triple therapy (SITT; fluticasone furoate/umeclidinium/vilanterol [FF/UMEC/VI] or beclomethasone dipropionate/glycopyrronium bromide/formoterol [BDP/GLY/FOR]) or multiple-inhaler triple therapy (MITT), using data from the AOK PLUS German sickness fund (1 January 2015-31 December 2019). The index date was the first date of prescription for FF/UMEC/VI or BDP/GLY/FOR (SITT users), or the first date of overlap of inhaled corticosteroid, long-acting ß2-agonist, and long-acting muscarinic antagonist (MITT users). Two cohorts were defined: the prevalent cohort included all identified triple therapy users; the incident cohort included patients newly initiating triple therapy for the first time (no prior use of MITT or SITT in the last 2 years). Patient characteristics and treatment patterns were assessed on the index date and during the 24-month pre-index period. Results: In total, 18,630 patients were identified as prevalent triple therapy users (MITT: 17,945; FF/UMEC/VI: 700; BDP/GLY/FOR: 908; non-mutually exclusive) and 2932 patients were identified as incident triple therapy initiators (MITT: 2246; FF/UMEC/VI: 311; BDP/GLY/FOR: 395; non-mutually exclusive). For both the prevalent and incident cohorts, more than two-thirds of patients experienced ≥1 moderate/severe exacerbation in the preceding 24 months; in both cohorts more BDP/GLY/FOR users experienced ≥1 moderate/severe exacerbation, compared with FF/UMEC/VI and MITT users. Overall, 97.9% of prevalent triple therapy users and 86.4% of incident triple therapy initiators received maintenance treatment in the 24-month pre-index period. Conclusion: In a real-world setting in Germany, triple therapy was most frequently used after maintenance therapy in patients with recent exacerbations, in line with current treatment recommendations.

Triple therapy (a combination of three different respiratory inhaled medications) is recommended for patients with chronic obstructive pulmonary disease (COPD) who experience repeated short-term symptom flare-ups when taking dual therapy (a combination of two different respiratory medications). Previously, patients had to take triple therapy using two or three separate inhalers. More recently, single-inhaler triple therapies have been developed, meaning patients can take all three different medications at the same time via one single inhaler. This study assessed the characteristics of patients who were already receiving triple therapy, or who started triple therapy (either via multiple inhalers or a single inhaler), in Germany between January 2015 and December 2019. In total, 18,630 patients who were already receiving triple therapy during the study period, and 2932 patients who newly started using triple therapy were included. The study reported that more than two-thirds of included patients had experienced at least one flare-up of COPD symptoms in the 2 years before starting triple therapy. Most patients had also received another therapy for COPD before starting triple therapy. A small proportion of patients started taking triple therapy after receiving no other therapy for COPD in the previous 2 years. The results of the study suggest that triple therapy for COPD in Germany is most often used in accordance with recommendations (patients already receiving therapy and experiencing repeated symptom flare-ups).

Comparing the risk of serious infections in patients with and without MS: A German claims data analysis.

BACKGROUND: Research suggests that serious infections (SIs), comorbidities, and advanced disability represent key drivers of early death in people with Multiple Sclerosis (pwMS). Nevertheless, further research is warranted to better characterize and quantify the risk of SI among pwMS compared to the general population. METHODS: Our study consisted of a retrospective analysis of claims data provided by a German statutory health insurance fund, AOK PLUS, covering 3.4 million individuals in Saxony and Thuringia from 01/01/2015-31/12/2019. A propensity score (PS) matching method was used to compare the incidence of SIs among people with and without MS. PwMS were required to have ≥1 inpatient or ≥2 confirmed outpatient diagnoses of MS (ICD-10 G35) from a neurologist from 01/01/2016-31/12/2018, while people from the general population could not have any inpatient/outpatient codes for MS during the entire study period. The index date was defined as the first observed MS diagnosis or, in the case of the non-MS cohort, a randomly assigned date within the inclusion period. For both cohorts a PS was assigned, corresponding with their probabilistic likelihood of having MS based on observable factors including patient characteristics, comorbidities, medication use and other variables. People with and without MS were matched using a 1:1 nearest neighbor strategy. An exhaustive list of ICD-10 codes was created in association with 11 main SI categories. SIs were those recorded as the main diagnosis during an inpatient stay. ICD-10 codes from the 11 main categories were sorted into smaller classification units, used to distinguish between infections. A 60-day threshold for measuring new cases was defined to account for the potential risk of re-infection. Patients were observed until the end of the study period (31/12/2019) or death. Cumulative incidence, incidence rates (IRs) and IR ratios (IRRs) were reported during follow-up and at 1-, 2- and 3-years post-index. RESULTS: A total of 4250 and 2,098,626 patients were included in the unmatched cohorts of people with and without MS. Ultimately, one match was identified for all 4,250 pwMS, corresponding with a final population of 8,500 patients. On average, patients were 52.0/52.2 years in the matched MS/non-MS cohorts; the gender breakdown was 72% female. Overall, IRs of SIs per 100 patient years (PY) were higher in pwMS than in those without MS (1 year: 7.6 vs. 4.3; 2 years: 7.1 vs. 3.8; 3 years: 6.9 vs. 3.9). During follow-up, the most common infection types in pwMS were of a bacterial/parasitic origin (2.3 per 100 PY), followed by respiratory (2.0) and genitourinary (1.9) infections. Respiratory infections were most common in patients without MS (1.5 per 100 PY). Differences in the IRs of SIs were statistically significant (p<0.01) at each measurement window, with IRRs ranging from 1.7-1.9. PwMS had a higher risk of hospitalized genitourinary infections (IRR: 3.3-3.8) and bacterial/parasitic infections (2.0-2.3). CONCLUSIONS: The incidence of SIs is much higher in pwMS, than comparators from the general population in Germany. Differences in hospitalized infection rates were largely driven by higher levels of bacterial/parasitic and genitourinary infections in the MS population.

Serious infections in patients with relapsing and progressive forms of multiple sclerosis: A German claims data study.

BACKGROUND: People with multiple sclerosis (pwMS) have a higher risk of serious infection (i.e., infection-related hospitalizations) than people without MS. Few studies have explored the risk of serious infections by MS phenotype in a real-world setting. This retrospective study compared the incidence of serious infections among people with relapse remitting MS (RRMS), primary progressive MS (PPMS), and secondary progressive MS (SPMS). METHODS: Adult pwMS were selected from a German claims database, based on one inpatient or two outpatient diagnoses of MS (ICD-10 G35) by a neurologist from 01/01/2016 to 12/31/2018. Three cohorts (RRMS, PPMS, SPMS) were identified based on codes for MS subtypes included in the German Modification of the ICD-10 system. A fourth cohort of unspecified MS patients combined those with conflicting MS subtype diagnoses and multiple unspecified codes for MS. Serious infections were defined as hospitalizations for which infections were selected as the primary inpatient diagnosis. Infections were identified from a basket of ICD-10 codes distributed across 11 main categories, according to possible pathogen (e.g., other bacterial diseases [A30-A49]) or anatomical location (e.g., urinary tract infection [N39.0]). Multiple infections were counted if an interval of at least 60 days was recorded between episodes. Serious infections were counted from index (i.e., first recorded MS code) until the end of the study period or death. Incidence rates (IRs) were reported per 100 patient years (PY). RESULTS: A total of 4,250 pwMS (RRMS: 2,307, PPMS: 282, SPMS: 558, unspecified MS: 1,135) were included; 32 patients progressed from RRMS to SPMS during the follow-up period. Mean (SD) age at baseline was 46.6 (13.6), 61.9 (12.4), and 62.5 (11.8) years in patients with RRMS, PPMS, and SPMS, respectively. Most pwMS were female (RRMS 74.8%, PPMS 62.1%, SPMS 67.4%). Progressive pwMS were more likely to have at least 1 comorbidity (PPMS 87.2%, SPMS 87.5%) compared to those with relapsing MS (61.9%). Most RRMS patients received disease-modifying therapy during follow-up (82.1%), while less than half of progressive MS patients did (PPMS 23.8%, SPMS 31.4%). Over a mean (SD) follow-up period of 3.5 (0.8) years, the IR of serious infections per 100 PY was higher in progressive MS cohorts (PPMS 13.5 [11.3-16.1], SPMS 13.6 [12.0-15.3]) than in the RRMS group (3.4 [3.0-3.7]). Yearly IRs remained stable over time in each cohort. Where anatomical location was specified, respiratory (2.0 per 100 PY) and genitourinary (1.9 per 100 PY) infections were most common. Across all subtypes, higher rates of serious infections were observed in men and older patients. CONCLUSION: Progressive MS, older age and male sex are associated with an increased risk of serious infections. Overall, respiratory and genitourinary infections were the most commonly reported serious infections.

Assessment of Metastatic Colorectal Cancer Patients' Preferences for Biologic Treatments in Germany Using a Discrete Choice Experiment.

BACKGROUND: Current treatment regimens for metastatic colorectal cancer (mCRC) include biologics such as epidermal growth factor receptor and vascular endothelial growth factor inhibitors, which have specific side-effect profiles. There is a lack of information on mCRC patient preference in Germany regarding biologics in combination with chemotherapy. This study aims to identify German mCRC patients' preference for these treatments PATIENTS AND METHODS: This was a multicenter cross-sectional discrete choice experiment (DCE). Data were collected using electronic case report forms and structured phone interviews. DCE attributes were related to efficacy, side effects, frequency of administration, and distance to treating physicians' practice. Patients' characteristics and choices were analyzed descriptively. Choice data was modeled using a random utility maximization framework. RESULTS: All attributes, except distance to treating physicians' practice, had a significant impact on patients' decision. The most important driver of patients' treatment decision was overall survival, followed by safety-related attributes and frequency of administration. Overall survival was the main driver in all subgroups analyzed. Risk of severe skin toxicities was more important to women, than men. In patients with prior experience of side effects, the risk of side effects accounted for 45% of a patient's decision, compared to 35% in those without prior experience. CONCLUSION: Overall survival remains the most important driver in mCRC patients' preferences for biologic treatment in combination with chemotherapy. Attributes related to safety were less important to patients when considering their treatment decision. These results indicate that understanding patient preferences may lead to increased treatment compliance.

Extent of non-adherence and non-persistence in asthma patients: analysis of a large claims data set.

OBJECTIVE: The objective of this study was to assess non-adherence (NA) and non-persistence (NP) to long-acting asthma medications in Germany by differentiating between measurement of NA in periods of therapy continuation and measurement of NP in therapy-naïve patients. METHODS: We analyzed treatment adherence to long-acting asthma medication using German claims data for periods of treatment continuation based on the medication possession ratio (MPR) and the proportion of days covered. Persistence was assessed in treatment-naïve patients. Outcomes were observed from the date of the first to the last prescription within a 12-month period. Both NA and NP analyses considered prescription supply, using either defined daily dosages, or prescribed daily dosages derived from a medical chart review. RESULTS: We identified 52,508 asthma patients (mean age: 40.1, 58.4% female) who received at least two long-acting asthma prescriptions within 12 months; 50,660 treatment-naïve patients were included in the NP analysis (mean age: 39.7, 58.8% female). The mean 12-month MPR was 38.5% (89.4% NA according to MPR ≤ 80%) and the average proportion of days covered was 40.4% (85.9% NA). Agent-specific MPR and NA rates varied between 31.8% (91.8% NA) and 56.2% (71.6% NA). The average weighted-MPR increased to 53.1% when using the prescribed daily dosage. Based on a > 90-day gap definition, 86.7% of patients were considered non-persistent after 12 months (>180: 72.3%). When using prescribed daily dosages, NP rates ranged from 66.7 to 78.5%. CONCLUSION: High levels of treatment NA and NP indicate a substantial need to improve adherence and persistence to long-acting asthma medication in Germany.

Evaluating the Economic Burden of Relapses in Neuromyelitis Optica Spectrum Disorder: A Real-World Analysis Using German Claims Data.

INTRODUCTION: Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune disease of the central nervous system which causes recurrent relapses, resulting in blindness, paralysis, and spinal cord damage. This study sought to explore the real-world burden, treatment, and cost of NMOSD in Germany using claims data. METHODS: Our study consisted of a retrospective analysis of two anonymized health insurance datasets covering around 9 million patients in Germany from 01/01/2013 to 31/12/2019. NMOSD patients were identified using inpatient and outpatient International Classification of Diseases, Tenth Revision (ICD-10) diagnoses of neuromyelitis optica (NMO; G36.0) and relevant symptom codes. Active periods of disease were identified based on relapse events (including hospitalizations and acute treatment); healthcare resource utilization (HCRU) and direct costs were allocated to active and inactive periods based on treatment dates. Propensity score matching was used to compare HCRU and cost outcomes among patients with and without NMOSD. RESULTS: Overall, 130 patients were identified as having NMOSD (mean age: 46.84 years; 58% female). NMOSD patients recorded 16.52 active and 348.48 inactive days per patient year (PPY). HCRU and associated costs were approximately tenfold higher during active periods than during inactive periods, with the largest share of the cost difference driven by hospitalizations (€6424.09/€259.10 per active/inactive month) and outpatient drug prescriptions (€412.83/€271.58). Direct healthcare costs incurred by patients with NMOSD (€12,913.28 PPY) were approximately threefold higher than those incurred by patients without NMOSD (€4667.66 PPY). Costs of hospitalization (€6448.32/€1937.64 PPY) and outpatient prescriptions (€3335.67/€1037.64 PPY) contributed most strongly to the difference. CONCLUSION: Patients with NMOSD consume substantial healthcare resources and incur heavy costs during active disease phases. This study captured direct measurable healthcare costs and likely underestimates the real societal/emotional burden on patients and their families. Nevertheless, prevention of acute relapses represents one compelling strategy to minimize the economic burden of NMOSD in Germany.

Identifying the Causes Increasing the Risk of Non-Adherence in Adult Patients with Asthma: An Analysis Combining Patient Survey Data with German Claims Data.

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.

Poststroke epilepsy incidence, risk factors and treatment: German claims analysis.

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.

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.

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.

Persistence with Biologic Treatment in Patients with Inflammatory Bowel Disease: A German Claims Data Analysis.

OBJECTIVES: This study aimed to assess the real-world rates of treatment discontinuation and switching of biologic therapies in patients with inflammatory bowel disease (IBD). METHODS: A retrospective claims data analysis on all continuously insured adult IBD patients with initiation of a biologic therapy was conducted. Observation started with the date of the first prescription of index tumor necrosis factor α-inhibitors (anti-TNFα) or vedolizumab (VDZ) therapy and lasted 12 months. Non-persistence was assumed in case of a switch to another biologic or a treatment gap of >90 days. RESULTS: We included 1,248 IBD biologic treatment starters (502 adalimumab, 77 golimumab, 441 infliximab, 228 VDZ); 837/411 were biologic-naïve (bio-naïve)/ biologic-experienced (bio-experienced). Mean age of bio-naïve/bio-experienced anti-TNFα patients was 39.2/38.1 years (54.9%/56.7% female) and 42.6/37.8 years for VDZ patients (56.3%/54.9% female). Seven hundred and seventy-two patients (61.9%) were persistent with their index biologic therapy after 12 months (61.9%/61.8% bio-naïve/bio-experienced). Percentage of persistent patients was 69.7% for VDZ (65.6%/71.3%) and 60.1% for anti-TNFα (61.4%/55.5%). VDZ was associated with later non-persistence in a multivariable Cox regression analysis (hazard ratio 0.675; p = 0.003) compared to anti-TNFα. CONCLUSIONS: Only 60-70% of IBD -patients are still persistent with their biologic therapy after 12 months. VDZ therapy is associated with a higher persistence than anti-TNFα therapy in this analysis.

Estimated epidemiology of osteoporosis diagnoses and osteoporosis-related high fracture risk in Germany: a German claims data analysis.

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.

Real-world treatment and survival of patients with advanced non-small cell lung Cancer: a German retrospective data analysis.

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.