Publikationen

Mevius A, Wilke T, Fuchs A, Kloppenburg A, Engel S, Linder R, Breithardt G. Catheter Ablation Versus Antiarrhythmic Medication in Patients with Atrial Fibrillation: a Propensity-Matched Analysis Based on a German Claims Data Set.  J Cardio Vasc Med 2019, 5: 1-12

Abstract

Aims:

Main objective of our analysis was to assess the long-term clinical and health economics outcomes of catheter ablation versus antiarrhythmic medication therapy in Germany.

Methods:

We conducted a retrospective analysis of anonymized claims data covering the years 2010-2014. Patients with at least one diagnosis of AF and a minimum follow-up period of twelve months (excluding death) were included and assigned into two treatment groups: AF ablation and antiarrhythmic medication. To balance different patient characteristics in both groups, the final analysis was based on propensity score-matched (PSM) cohorts.

Results:

Of 498,253 AF patients, 2,404 could be assigned to the final analysis population – 1,202 patients in each group. The difference in the all-cause mortality rate reached statistical significance after 24 months of observation (1.5% versus 3.1% (p=0.015)) and after 36 months (1.7% versus 4.8% (p=0.005)). We could not identify any significant difference between the groups in cardiovascular events (amongst others stroke, TIA, myocardial infarction) over the three-year observation period. Direct cardiology-associated healthcare costs after index date (excluding catheter ablation procedure) were significantly different between the groups in the first and third observational year (third-year costs of €1,618 in the ablation group versus €2,462 in the medication group; p<0.007).

Conclusion:

Over a period of 36 months, all-cause mortality in AF patients who underwent catheter ablation was found to be significantly lower compared to AF patients who received antiarrhythmic medication. Direct cardiology healthcare costs after the ablation procedure proved to be consistently and significantly lower in comparison with medication therapy.

Brandes A, Groth A, Gottschalk F, Wilke T, Ratsch BA, Orzechowski HD, Fuchs A, Deiters B, Bokemeyer B. Real-world biologic treatment and associated cost in patients with inflammatory bowel disease. Z Gastroenterol. 2019 Jul;57(7):843-851

Abstract

OBJECTIVES:
This study aimed to describe biologic treatment of German inflammatory bowel disease (IBD) patients, including biologics' dosage, health care resource use, and treatment-associated cost.

METHODS:
In this retrospective claims data analysis, all continuously insured adult IBD patients (Crohn's disease [CD] or ulcerative colitis [UC]) who started a new therapy with an anti-tumor necrosis factor alpha (anti-TNF-α) or vedolizumab (VDZ) were included. Observation started with the date of the first prescription of index biologic therapy and lasted 12 months.

RESULTS:
In the database, 1248 out of 57 296 IBD patients started a biologic treatment of interest (1020 anti-TNF-α, 228 VDZ), and 837 patients were bio-naïve (773 anti-TNF-α, 64 VDZ). The mean age of bio-naïve/bio-experienced anti-TNF-α 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). The proportion of patients receiving a maintenance dosage > 150 % compared to SmPC was 15.1 % for Adalimumab, 5.2-39.0 % for Golimumab, 14.7-34.5 % for Infliximab, and 19.7 % for VDZ patients. During the maintenance phase, up to 58.8 % of patients received at least 1 prescription of any CS, and 41.7 %/47.1 % (anti-TNF-α/VDZ) were treated in a hospital due to IBD. The mean IBD-related direct health care cost per patient year was € 30 246 (anti-TNF-α)/ € 28 227 (VDZ) for bio-naïve patients (p = 0.288) and € 34 136 (anti-TNF-α)/ € 32 112 (VDZ) for bio-experienced patients (p = 0.011).

CONCLUSIONS:
A substantial percentage of patients receive a high biologic dosage in the maintenance phase. Despite biologic therapy, 30-40 % receive a CS therapy and/or experience at least 1 IBD-associated hospitalization within a year, possibly indicating a remaining disease activity.

Wilke T, Picker N, Mueller S, Geier S, Foersch J, Aberle J, Martin S, Riedl M, Gabler M. Real-world insulin therapy in German type 2 diabetes mellitus patients: patient characteristics, treatment patterns, and insulin dosage. Diabetes Metab Syndr Obes. 2019 Jul 24;12:1225-1237

Abstract

BACKGROUND:
A substantial share of type 2 diabetes mellitus (T2DM) patients receive insulin. However, little is known about the real-world treatment patterns around insulin initiation.

METHODS:
This was a retrospective claims data analysis. T2DM patients who initiated an insulin therapy between 01/01/2013 and 31/12/2015 were identified in the German AOK PLUS dataset. For validation of results, additional data on a similar T2DM patient population were collected in a Germany-wide medical chart review.

RESULTS:
A total of 284,878 T2DM patients were identified. Of these, 27,340 (9.6%) initiated an insulin treatment during the inclusion period (mean age: 72.2 years; 51.4% female). Mean/median weight and BMI of patients with available clinical data was 85.8/84.0 kg (SD:18.9) and 30.6/29.8 kg/m2 (SD:6.1), respectively at baseline. Mean/median HbA1c-value at baseline was 8.4/8.0% (SD: 1.8). Most commonly prescribed antidiabetic drugs (AD) within 6 months before insulin initiation were metformin (MET; 54.0%), DPP-4 inhibitors (DPP-4i; 37.6%), and sulfonylureas (SU; 29.5%). As high as 23.2% of the patients did not receive any AD prescription within 6 months before insulin initiation. A total of 10,953 of above 27,340 insulin starters (40.1%) initiated their insulin therapy without concomitant ADs (insulin monotherapy); 43% of these patients did not receive any AD before insulin initiation. Of the remaining 16,387 patients (59.9%), 4070 patients (14.9%) received MET only as concomitant AD, 6385 (23.4%) received MET plus at least one further AD, and 5932 (21.7%) received at least one further AD excluding MET. Throughout the first year of treatment, prescribed insulin dosage increased over time, resulting in approximately 43.3-77.9 IUs per observed patient day after 12 months of insulin treatment.

CONCLUSIONS:
Characteristics of German T2DM patients initiating insulin deviate substantially from the average German population, especially in terms of weight. We identified an unexpectedly high number of patients without previous AD therapy receiving insulin monotherapy, which is not in line with the clinical guidelines.

Wilke T, Mueller S, Bauer S, Pitura S, Probst L, Ratsch BA, Salwender H.  Treatment of relapsed refractory multiple myeloma: which new PI-based combination treatments do patients prefer? Patient Prefer Adherence. 2018 Nov 9;12:2387-2396

Abstract

BACKGROUND AND OBJECTIVES:
This study describes preferences of German relapsed refractory multiple myeloma (RRMM) patients with novel proteasome inhibitor-based combination treatments.

METHODS:
Patients with a minimum age of 18 years and a diagnosis of RRMM were included. Their preferences were assessed using a discrete choice experiment design, which was developed based on a literature review and two patient focus group discussions. The final discrete choice experiment design consisted of four attributes, namely "therapy application regimen," "time without progression of disease," "possibility of grade ≥3 adverse events (AEs) affecting the blood," and "possibility of grade ≥3 AE heart failure."

RESULTS:
Analysis was based on 84 patients (36.9% females, mean age 62.7 years, mean multiple myeloma disease duration 5.5 years). Among the tested attributes, "therapy application regimen" was assigned the highest importance for treatment decisions (38.8%), the second important attribute was "time without progression of disease" (38.7%), followed by "possibility of AE heart failure" (13.9%) and "possibility of AEs affecting the blood" (8.6%). Patients preferred oral intake once a day and once a week over other application modes such as oral intake once a day and once a week plus twice-weekly infusions. Furthermore, they preferred longer disease progression-free time and lower risk of grade ≥3 AEs. The highest overall utility was derived for ixazomib + lenalidomide + dexamethasone (utility: 3.218), compared with lenalidomide + dexamethasone (2.769), and carfilzomib + lenalidomide + dexamethasone (1.928).

CONCLUSION:
RRMM patients prefer treatments with an all-oral application, a longer disease-progression-free time, and a lower probability of AEs. If patients face tradeoffs, they accept a lower progression-free time and/or higher AE rates to get an all-oral therapy.

Mueller S, Gottschalk F, Groth A, Meeraus W, Driessen M, Kohlmann T, Wilke T.  Primary data, claims data, and linked data in observational research: the case of COPD in Germany . Respiratory Research (2018) 19:161

Abstract

Background
Real-world evidence (RWE) can inform patient management decisions, but RWE studies are associated with limitations. Linkage of different RWE data types could address such limitations by enriching data and improving scientific quality. Using the example of chronic obstructive pulmonary disease (COPD) in Germany, this study assessed the value of data linkage between primary and secondary data sources for RWE.

Methods
Post hoc analysis of data from an observational RWE study, which used prospectively collected data and data from an insurance claims database to assess treatment adherence and persistence in patients with COPD in Germany. Patient-level primary data were collected from the prospective observational study (primary dataset, N = 636), and claims data from the sickness fund AOK Nordost (claims dataset, N = 74,916). Primary and claims data were linked at a patient level using insurance numbers (linked dataset). Patients in the linked dataset were indexed at date of study inclusion for primary data and matched calendar date for claims data. Agreement between primary and claims data was examined for patients in the linked dataset based on comparisons between recorded sociodemographic data at index, comorbidities (primary: any recorded; claims: pre-index), prescriptions for COPD therapies (type and date) and exacerbations in the 12-month post-index period.

Results
The linked dataset included primary and claims data for 536 patients. Fewer comorbid patients were reported in primary data compared with claims data (p < 0.001), with overall agreement between 63.6% (hypertension) and 90.5% (osteoporosis). Number of prescriptions for COPD therapies per patient was lower in primary versus claims data (3.7 vs 10.3 prescriptions, respectively), with only 24.5% of prescriptions recorded in both datasets. Only 11.5% of exacerbations (moderate or severe) were recorded in both datasets, with 15.5% recorded only in primary data and 73.0% recorded only in claims data.

Conclusion
Our study highlighted discrepancies between primary and claims data capture for this population of German patients with COPD, with lower reporting of comorbidities, COPD therapy prescriptions and exacerbations in primary versus claims data. Study findings suggest that data linkage of primary and claims data could provide enrichment and be useful in fully describing COPD endpoints.

Wilke T, Mueller S, Bloempott S, Rimle M, Amann-Vesti B, Schaefer S.  Präferenzen von Patienten mit Vorhofflimmern bezüglich der Therapieeigenschaften von oralen Antikoagulanzien: Ein Discrete-Choice-Experiment in der Schweiz. ARS MEDICI (2018) 13:605-606

Abstract

Einleitung und Studienziele
Aktuelle Leitlinien zur Behandlung von Vorhofflimmern (VHF) empfehlen bei einem erhöhten Schlaganfallrisiko eine lebenslange orale Antikoagulation (OAK). Als OAK-Alternativen stehen Vitamin-K-Antagonisten (VKA) sowie seit einigen Jahren auch neue orale Antikoagulanzien (NOAK: Dabigatran, Rivaroxaban, Apixaban, Edoxaban) zur Verfügung. In klinischen Studien konnte gezeigt werden, dass NOAK in Bezug auf Effektivität und Sicherheit einer gut esteuerten VKA-Antikoagulation statistisch nicht unterlegen sind. Präferenzstudien haben zudem gezeigt, dass VKA und NOAK auch aus Sicht von VHF-Patienten bedeutende Unterschiede aufweisen. Aus Patientensicht haben
nämlich auch die sogenannten «weichen Therapieeigenschaften» wie Verabreichungsform, notwendige Begleitmassnahmen (Blutkontrollen) oder die Lebensqualität einschränkende Restriktionen eine hohe Bedeutung. Dementsprechend empfehlen die aktuellen ESC-Leitlinien zur OAK bei VHF explizit, auch die Patientenpräferenzen
bei der Therapieentscheidung zu berücksichtigen. Ziel der vorliegenden Studie war, anhand einer Patientenpräferenzuntersuchung zu ermitteln, welche Eigenschaften eines oralen Antikoagulans von VHF-Patienten in der Deutschschweiz bevorzugt werden.

Mueller S, Groth A, Spitzer SG, Schramm A, Pfaff A, Maywald U. Real-world effectiveness and safety of oral anticoagulation strategies in atrial fibrillation: a cohort study based on a German claims dataset. Pragmat Obs Res. 2018 May 1;9:1-10

Abstract

OBJECTIVE:
To compare the real-world effectiveness and safety of non-vitamin-K-antagonist oral anticoagulant (NOAC) treatment in atrial fibrillation (AF) patients with a vitamin-K-antagonist (VKA)-based treatment.

METHODS:
This was a retrospective analysis of an anonymized claims dataset from 3 German health insurance funds covering the period from January 01, 2010 to June 30, 2014, with a minimum observation time of 12 months. All continuously insured patients with at least 2 outpatient AF diagnoses and/or 1 inpatient respective diagnosis who received at least 1 outpatient prescription of a NOAC or VKA were included.

OUTCOMES AND MEASURES:
Death, ischemic strokes (IS), non-specified strokes, transient ischemic attacks (TIAs), myocardial infarctions (MIs), arterial embolism (AE), hemorrhagic strokes, severe bleedings, and composite outcomes. Main comparisons were done based on propensity score-matched (PSM) cohorts. Results were reported as incidence rate ratios and hazard ratios (HRs).

RESULTS:
We assigned 37,439 AF patients to each PSM cohort (NOAC cohort: mean age 78.2 years, mean CHA2DS2VASc score 2.96, mean follow-up 348.5 days; VKA cohort: mean age 78.2 years, mean CHA2DS2VASc 2.95, mean follow-up 365.5 days). NOAC exposure was associated with significantly higher incidence rate ratios; 95% CI/HRs; 95% CI for the following outcomes: death (1.22; 1.17-1.28/1.22; 1.17-1.28), IS (1.90; 1.69-2.15/1.92; 1.69-2.19), non-specified strokes (2.04; 1.16-3.70/1.93; 1.13-3.32), TIAs (1.52; 1.29-1.79/1.44; 1.21-1.70), MIs (1.26; 1.10-1.15/1.31; 1.13-1.52), AE (1.75; 1.32-2.32/1.81; 1.36-2.34) and severe bleeding (1.92; 1.71-2.15/1.95; 1.74-2.20). Multivariable Cox regression analyses and additional sensitivity analysis, including analysis of PSM-matched NOAC/VKA treatment-naive patients, only confirmed the above results. The study was documented under clinicaltrials.gov (NCT02657616).

CONCLUSION AND RELEVANCE:
A VKA therapy seems to be more effective and safer than a NOAC therapy in a real-world cohort of German AF patients.

Wilke T, Groth A, Fuchs A, Pfannkuche M, Maywald U. Persistence with VKA treatment in newly treated atrial fibrillation patients: an analysis based on a large sample of 38,076 German patients. Eur J Clin Pharmacol. 2017 Nov;73(11):1437-1447

Abstract

PURPOSE:
The aim of this study was to describe persistence with vitamin K antagonist (VKA) treatment in German atrial fibrillation (AF) patients and to identify factors which may be associated with early discontinuation of VKA therapy.

METHODS:
We did a retrospective cohort study based on an anonymized German claims dataset with VKA treatment-naïve AF patients, who received at least one VKA prescription. VKA therapy discontinuation was defined as a gap >180 days.

RESULTS:
We identified 38,076 VKA patients who started a VKA therapy (mean age 76.13 years; 56.08% female; mean CHA2DS2-VASc-Score 4.49; mean Charlson Comorbidity Index (CCI) 3.91). After four quarters since start of VKA treatment, 14,889 (39.10%) of observed patients had discontinued their VKA treatment (after eight quarters: 54.61%). Mean time until treatment discontinuation was 390.55 days. Risk of VKA discontinuation increased with the diagnosis of dementia within the first two quarters of VKA treatment [HR 1.35 (95% CI 1.29-1.40)], diagnosed alcohol or drug abuse in the baseline period [HR 1.25; 95% CI 1.18-1.33)], female gender [HR 1.08; 95% CI 1.05-1.10)], higher age (HR 1.03; 95% CI 1.03-1.03), higher CCI (HR 1.05; 95% CI 1.04-1.05), any prescription of NSAID (HR 1.07; 95% CI 1.04-1.10), and number of surgeries in the first two quarters of VKA treatment (HR 1.05; 95% CI 1.04-1.05). At least one yearly visit to a cardiologist since start of VKA treatment decreased the risk of non-persistence [HR 0.90; 95% CI 0.88-0.93] and a cancer diagnosis in the baseline period (HR 0.92; 95% CI 0.89-0.96).

CONCLUSION:
Non-persistence related to VKA therapy is common in AF patients. Older more comorbid female patients as well as patients who face surgeries and who do not visit a cardiologist regularly face a higher therapy discontinuation risk.

Mueller S, Ehlken C, Bauer-Steinhusen U, Lechtenfeld W, Hasanbasic Z, Agostini H, Wilke T.  Treatment of age-related neovascular macular degeneration: the patient's perspective. Graefes Arch Clin Exp Ophthalmol. 2017 Nov;255(11):2237-2246

Abstract

OBJECTIVES:
The aim of this study was to assess patients' views and expectations with regard to neovascular age-related macular degeneration (nAMD) and intravitreal anti-VEGF therapy (IVT).

METHODS:
We conducted a multicenter, non-interventional, prospective cohort study including nAMD patients treated with IVT in Germany. Patients with at least one IVT before study enrollment and aged ≥50 years were included. Three telephone interviews were conducted during a 12-month observational period. Here, patient's beliefs/expectations with regard to the nAMD disease and the IVT treatment were discussed. Only patients who completed all three phone interviews were included in the analyses. We used a two-step cluster analysis to identify patient clusters regarding specific patient attitudes towards nAMD and its treatment.

RESULTS:
Three hundred and thirty-two patients completed all interviews (mean age of 76.4 ± 7.2 years, 59.0% women). Out of these, 57.8% acknowledged that they needed general assistance in daily life, while 77.4% stated being able to attend general medical appointments on their own. However, 64.7% needed a driver or an accompanying person to attend their IVT appointments. In addition, 3.9% of the patients were afraid of IVT side effects. Also, 87.3% and 43.1% of the patients could name their disease or the anti-VEGF drug administered, respectively. More than three-quarters of the patients (83.1%) were aware of possible consequences of nAMD by stating vision loss or blindness, but only 16.6% knew that nAMD is a chronic disease. Generally, patients were optimistic: 70.2%, 5.1% and 13.0% of them expected stable visual acuity (VA), a significant improvement or expected worsening of VA in the next year, respectively. Almost two thirds of patients who provided their therapy expectations (47.0%) anticipated fewer injections/discontinuation of IVT. We identified five patient clusters differing significantly from each other with regard to four variables: being afraid of IVT, nAMD disease awareness, optimism with regard to effectiveness of IVT, and nAMD disease and treatment knowledge.

CONCLUSIONS:
Only a minority of patients is aware of the chronic nature of nAMD. To motivate patients to accept a life-long IVT treatment, physicians and caregivers must know that there exist different patient types with significant differences in communication needs.

Wilke T, Mueller S, Lee SC, Majer I, Heisen M.  Drug survival of second biological DMARD therapy in patients with rheumatoid arthritis: a retrospective non-interventional cohort analysis. BMC Musculoskelet Disord. 2017 Aug 2;18(1):332

Abstract

BACKGROUND:
Since persistence to first biological disease modifying anti-rheumatic drugs (bDMARDs) is far from ideal in rheumatoid arthritis (RA) patients, many do receive a second and/or third bDMARD treatment. However, little is known about treatment persistence of the second-line bDMARD and it is specifically unknown whether the mode of action of such a treatment is associated with different persistence rates. We aimed to assess discontinuation-, re-initiation- or continuation-rates of a 2nd bDMARD therapy as well as switching-rates to a third biological DMARD (3rd bDMARD) therapy in RA patients.

METHOD:
Analysis was based on German claims data (2010-2013). Patients were included if they had received at least one prescription for an anti-TNF and at least one follow-up prescription of a 2nd bDMARD different from the first anti-TNF. Patient follow-up started on the date of the first prescription for the 2nd bDMARD and lasted for 12 months or until a patient's death.

RESULTS:
2667 RA patients received at least one anti-TNF prescription. Of these, 451 patients received a second bDMARD (340 anti-TNF, mean age 52.6 years; 111 non-anti-TNF, mean age 55.9 years). During the follow-up, 28.8% vs. 11.7% of the 2nd anti-TNF vs. non-anti-TNF patients (p < 0.001) switched to a 3rd bDMARD; 14.1% vs. 19.8% (p = 0.179) discontinued without re-start; 3.8% vs.1.8% (p = 0.387) re-started and 53.5 vs. 66.7% (p < 0.050) continued therapy. Patients in the non-anti-TNF group demonstrated longer drug survival (295 days) than patients in the anti-TNF group (264 days; p = 0.016). Independent variables associated with earlier discontinuation (including re-start) or switch were prescription of an anti-TNF as 2nd bDMARD (HR = 1.512) and a higher comorbidity level (CCI, HR = 1.112), whereas previous painkiller medication (HR = 0.629) was associated with later discontinuation or switch.

CONCLUSIONS:
Only 56.8% of RA patients continued 2nd bDMARD treatment after 12 months; 60% if re-start was included. Non-anti-TNF patients had a higher probability of continuing 2nd bDMARD therapy.