Publikationen

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.

Mueller S, Wilke T, Fuchs A, Maywald U, Flacke JP, Heinisch H, Krueger K.  Non-persistence and non-adherence to MTX therapy in patients with rheumatoid arthritis: a retrospective cohort study based on German RA patients. Patient Prefer Adherence. 2017 Jul 20;11:1253-1264

Abstract

OBJECTIVE:
This study aimed to assess the level of nonpersistence (NP) and nonadherence (NA) to methotrexate (MTX) therapy in German patients with rheumatoid arthritis (RA).

MATERIALS AND METHODS:
Based on German claims data, RA patients who received a MTX therapy (subgroup: treatment-naive patients) were analyzed. NP was defined as treatment gap >12 weeks. Regarding NA, it is the overall medication possession ratio (MPR) during an observational period of 12 or 24 months after therapy, and the MPR is calculated only for the periods of therapy continuation; NA was defined as MPR <80%.

RESULTS:
A total of 7,146 RA patients who received at least one MTX prescription (subgroup: 1,211 treatment-naive patients) could be observed (mean age: 64.4 years, 73.6% female). Percentage of NP patients among MTX-naive patients after 6, 12 and 18 months was 16.7%, 34.0% and 36.7%, respectively. After MTX therapy discontinuation, 39.9% had restarted their MTX therapy, 13.8% had received another non-MTX synthetic disease-modifying antirheumatic drug (sDMARD), 8.1% had biological DMARD (bDMARD) and 49.2% had not received any DMARD prescription at all. Overall, 12- and 24-month MPRs for MTX therapy were 83.0% and 76.5% with a percentage of NA patients of 25.8% and 33.8%, respectively. During periods of general treatment continuation, the percentage of patients with an MPR <80% was 6.5%.

CONCLUSION:
NP to MTX treatment seems to be common in one-fourth of German patients with RA. An additional number of patients, at least 6.5%, are also affected by NA. A considerable percentage of RA patients who discontinued MTX therapy do not receive any follow-up DMARD therapy.

Wilke T, Bauer S, Mueller S, Kohlmann T, Bauersachs R.  Patient Preferences for Oral Anticoagulation Therapy in Atrial Fibrillation: A Systematic Literature Review. Patient. 2017 Feb;10(1):17-37

Abstract

OBJECTIVES:
Since the introduction of non-vitamin K antagonist (VKA) oral anticoagulants (NOACs), an additional treatment option, apart from VKAs, has become available for stroke prevention in patients with atrial fibrillation (AF). For various reasons, it is important to consider patients' preferences regarding type of medication, particularly in view of the established relationship between preferences towards treatment, associated burden of treatment, and treatment adherence. This review aimed to systematically analyse the scientific literature assessing the preferences of AF patients with regard to long-term oral anticoagulant (OAC) treatment.

METHODS:
We searched the MEDLINE, Scopus and EMBASE databases (from 1980 to 2015), added records from reference lists of publications found, and conducted a systematic review based on all identified publications. Outcomes of interest included any quantitative information regarding the opinions or preferences of AF patients towards OAC treatment, ideally specified according to different clinical or convenience attributes describing different OAC treatment options.

RESULTS:
Overall, 27 publications describing the results of studies conducted in 12 different countries were included in our review. Among these, 16 studies analysed patient preferences towards OACs in general. These studies predominantly assessed which benefits (mainly lower stroke risk) AF patients would require to tolerate harms (mainly higher bleeding risk) associated with an OAC. Most studies showed that patients were willing to accept higher bleeding risks if a certain threshold in stroke risk reduction could be reached. Nevertheless, most of the publications also showed that the preferences of AF patients towards OACs may differ from the perspective of clinical guidelines or the perspective of physicians. The remaining 11 studies included in our review assessed the preferences of AF patients towards specific OAC medication options, namely NOACs versus VKAs. Our review showed that AF patients prefer easy-to-administer treatments, such as treatments that are applied once daily without any food/drug interactions and without the need for bridging and frequent blood controls.

CONCLUSION:
Stroke risk reduction and a moderate increase in the risk of bleeding are the most important attributes for an AF patient when deciding whether they are for or against OAC treatment. If different anticoagulation options have similar clinical characteristics, convenience attributes matter to patients. In this review, AF patients favour attribute levels that describe NOAC treatment.

Mueller S, Wilke T, Bechtel B, Punekar YS, Mitzner K, Virchow JC.  Non-persistence and non-adherence to long-acting COPD medication therapy: A retrospective cohort study based on a large German claims dataset.  Respir Med. 2017 Jan;122:1-11

Abstract

OBJECTIVES:
The main objectives of this study, based on a large cohort of German COPD patients, were to assess the level of non-persistence (NP) and non-adherence (NA) with long-acting COPD inhaler treatment and to describe factors that may be associated with NP and NA.

METHODS:
This was a retrospective cohort analysis based on claims data provided by a German statutory health insurance fund (years 2010-2012). NP was analyzed for treatment-naïve patients only; it was defined as a gap of >90 days in medication availability. With regard to NA, first the overall yearly medication possession ratio (MPR) was analyzed, NA was defined as MPR<80%. Secondly, adherence was explored only for the period in which a patient continued therapy with a long-acting COPD agent (no gap>90 days).

RESULTS:
45,937 COPD patients who received at least one prescription of any long-acting COPD agent were identified (mean age 71.4 years; 45.2% female). Among these, 22,276 (42.4%) were classified as newly treated. The percentage of NP patients after 12 months was 65.3% on an overall patient level. Agent-specific NP rates were: 58.5% for LABA, 47.9% for LAMA, 78.0% for ICS, and 69.4% for single-device LABA/ICS combination treatment. The overall 12-month MPR across all agent classes on a patient level was 57.9% (70.0% of patients classified as non-adherent). During periods of general treatment continuation, the mean MPR/NA rates were 85.0%/30.1% (patient level across all agents), 89.3%/28.2% (LABA), 92.1%/16.2% (LAMA), 84.2%/43.8% (ICS) and 84.1%/42.8% (LABA/ICS combination). In the Cox regression analyses, several factors like female gender, higher CCI or lower number of specialist' visits were associated with earlier discontinuation of therapy. In comparison to LABA therapy, LAMA therapy was less likely to be associated with early NP, whereas patients who initiated ICS therapy or a single-device LABA/ICS combination therapy faced a higher NP risk.

CONCLUSIONS:
In German COPD patients, persistence and adherence with respect to long-acting bronchodilator therapy is poor. Approximately two thirds of patients fail to continue treatment after 12 months. In addition, about one third implement their treatment poorly during periods of general therapy continuation.

Wilke T, Mueller S, Groth A, Berg B, Hammar N, Tsai K, Fuchs A, Stephens S, Maywald U.  Effectiveness of sulphonylureas in the therapy of diabetes mellitus type 2 patients: an observational cohort study.  J Diabetes Metab Disord. 2016 Aug 2;15:28

Abstract

BACKGROUND:
We compared all-cause mortality, major macrovascular events (MACE) and diabetes-related hospitalizations in T2DM-incident patients newly treated with metformin (MET) versus sulphonylureas (SU) monotherapy and in T2DM-prevalent patients newly treated with MET+SU versus MET+DPP4-inhibitor combination therapy.

METHODS:
We analysed anonymized data obtained from a German health fund. Patients were included when they had started MET versus SU therapy or MET+SU versus MET+DPP4 therapy between 01/07/2010 and 31/12/2011. Observation started with the first MET/SU prescription or the first prescription of the second agent of a MET+SU/MET+DPP4 combination therapy. Follow-up time lasted until the end of data availability (a minimum of 12 months), death or therapy discontinuation.

RESULTS:
In total, 434,291 T2DM-prevalent and 35,661 T2DM-incident patients were identified. Of the identified T2DM-incident patients, 904/7,874 started SU/MET monotherapy, respectively, with a mean age of 70.1/61.4 years (54.6/50.3 % female; Charlson Comorbidity Index (CCI) 1.4/2.2; 933/7,350 observed SU/MET patient years). 4,157/1,793 SU+MET/DPP4+MET therapy starters had a mean age of 68.1/62.2 years (53.4/50.8 % female; CCI 2.8/2.6; 4,556/1,752 observed SU+MET/ DPP4+MET patient years). In a propensity score matched (PSM) comparison, the HRs (95 % CIs) associated with SU monotherapy compared to MET monotherapy exposure were 1.4 (0.9-2.3) for mortality, 1.4 (0.9-2.2) for MACE, 4.1 (1.5-10.9) for T2DM hospitalizations and 1.6 (1.2-2.3) for composite event risk. In a multivariable Cox regression model, SU monotherapy was associated with higher mortality (aHR 2.0; 1.5-2.6), higher MACE (aHR 1.3; 1.0-1.7) and higher T2DM hospitalizations (aHR 2.8; 1.8-4.4), which corresponded with a higher composite event risk (aHR 1.8; 1.5-2.1). No significant differences in event rates were observed in the PSM comparison between DPP4+MET/SU+MET combination therapy starters and in the multivariable Cox regression analysis.

CONCLUSIONS:
Our results show that SU monotherapy may be associated with increased mortality, MACE and T2DM hospitalizations, compared to MET monotherapy. When considering SU therapy, the associated cardiovascular risk should also be taken into account.

Wilke T, Mueller S, Groth A, Berg B, Fuchs A, Sikirica M, Logie J, Martin A, Maywald U.  Non Persistence and Non-Adherence of Patients with Type 2 Diabetes Mellitus in Therapy with GLP-1 Receptor Agonists: A Retrospective Analysis. Diabetes Research. March 2016, Volume 7, Issue 1, pp 105-124

Abstract

Introduction

Our main aim was to assess the level of persistence and adherence to therapy with glucagon-like peptide-1 (GLP-1) receptor agonists in type 2 diabetes mellitus (T2DM) patients in the United Kingdom (UK) and Germany, also by comparing once- (OD) with twice-a-day (BID) therapy.

Methods

We used two large retrospective datasets: a German claims dataset and the UK General Practitioner (GP)-based Clinical Practice Research Datalink (CPRD) dataset (2010–2012). All continuously insured T2DM patients with at least one outpatient/inpatient T2DM diagnosis were observed starting with the first prescription of a GLP-1 receptor agonist. Non-persistence (NP) was defined as treatment gap >90 days. Non-adherence (NA) was defined as medication possession ratio <80%, calculated during a period in which a patient continued therapy (no treatment gap >90 days) only.

Results

In the UK sample, 1905 T2DM patients started a treatment with GLP-1 receptor agonists (mean age: 55.5 years, 47.2% female). In the German sample, 1627 T2DM patients started a treatment with GLP-1 receptor agonists (mean age: 56.6 years, 51.4% female). Percentage of NP patients after 12 months was 29.5% in the UK and 36.4% in the German sample. In both countries, a BID treatment was associated with a higher probability to discontinue a treatment with GLP-1 receptor agonists earlier than an OD treatment (hazard ratio [HR] = 1.431 in UK and HR = 1.314 in Germany). The percentages of patients considered NA were 20.2%/20.0%/20.5% (all/OD/BID) for the UK sample, and 19.9%/19.2%/21.8% (all/OD/BID) for the German sample.

Conclusion

NP and NA to treatment with GLP-1 receptor agonists in both UK and Germany appear to be similar. Persistence to OD treatment is higher than to BID treatment in both the UK and Germany.p>

Mueller S, Agostini H, Ehlken C, Bauer-Steinhusen U, Hasanbasic Z, Wilke T. Patient Preferences in the Treatment of Neovascular Age-Related Macular Degeneration: A Discrete Choice Experiment. Ophthalmology. 2016 Apr;123(4):876-83

Abstract

PURPOSE:
The objective of our study was to investigate preferences of patients with neovascular age-related macular degeneration (nAMD) for different anti-vascular endothelial growth factor (VEGF) treatment schemes.

DESIGN:
We used a discrete choice experiment (DCE) design as part of a telephone interview.

PARTICIPANTS:
Patients with nAMD aged at least 50 years were included in the study.

METHODS:
Telephone interviews were done between November 2012 and October 2013.

MAIN OUTCOME MEASURES:
In our DCE survey, we measured patient preferences toward specific levels of attributes that describe different options in the everyday intravitreal injection treatment setting: (1) treatment scheme; (2) change of visual acuity (VA); and (3) time the patient needs for each visit to the eye specialist.

RESULTS:
A total of 284 patients with nAMD with a mean age of 77.4±7.1 years (women: 59.9%) completed the DCE interviews. Of them, 22.9% had poor VA at study inclusion, 54.9% had moderate VA, and 14.1% had good VA; VA was not available for 8.1% of the patients. Generally, patients preferred the attribute levels "improvement in VA" and "short time per specialist visit." The results for the attribute "treatment scheme" were inconclusive because none of the attribute levels (injections every 4 weeks, every 8 weeks, and pro re nata) were associated with statistically significant utility differences. This also mirrors the relative importance of the different attributes in patient decisions: "Change of VA" influenced decision making for a treatment option in 73.6% of cases; "waiting, treatment, and travel time" influenced decision making in 21.0% of cases; and "treatment scheme" influenced decision making for a treatment option in 5.4% of cases. To obtain improved VA instead of a worsening VA, patients in our study stated to be willing to accept a very long time needed per physician visit of 21.2 hours (8.5 hours for improved rather than stable VA and 12.7 hours for stable VA rather than worsening VA).

CONCLUSIONS:
To prevent deterioration of VA, patients with nAMD seem to be willing to accept a high treatment burden with regular intravitreal injections at short intervals and long periods of waiting, treatment, and traveling for their consultations.

Wilke T, Boettger B, Berg B, Groth A, Botteman M, Yu S, Fuchs A, Maywald U.  Healthcare Burden and Costs Associated with Urinary Tract Infections in Type 2 Diabetes Mellitus Patients: An Analysis Based on a Large Sample of 456,586 German Patients. Nephron. 2016;132(3):215-26

Abstract

OBJECTIVES:
We examined the real-world treatment of urinary tract infections (UTIs) in a type 2 diabetes mellitus (T2DM) population, evaluated UTI-related healthcare resource use and direct treatment costs, and assessed factors that may predict UTI-related costs.

METHODS:
We analyzed an anonymized dataset from a regional German healthcare fund (2010-2012). UTI-associated resource use was described by the number of UTI-associated outpatient visits, the number and length of UTI-related acute hospital visits, and the number of UTI-related antibiotics prescriptions. UTI-related direct treatment costs were studied both based on these resource use numbers and, additionally, based on a comparison of all-cause annual healthcare costs of T2DM-patients who were or were not affected by a UTI. To identify factors that might predict direct treatment costs related to UTI treatment, we conducted generalized linear regression model analyses (based on gamma distribution) using sociodemographic and clinical characteristics of observed patients as available in the database as independent variables.

RESULTS:
A total of 456,586 T2DM-patients were included with a mean age of 73.8, a percentage of 56.3 female patients, and a mean Charlson comorbidity index of 7.3. In our database, we observed 48,337 UTI events. The direct mean resource-based costs were €315.90 per UTI event. Older age, higher comorbidity status, at least one previous non-UTI infection, and poorer renal function were associated with higher costs, while female gender and at least one previous UTI event were associated with lower costs. In the all-cause cost analysis, healthcare costs per patient year were €3,916 higher in the UTI group than in the non-UTI group.

CONCLUSION:
Our study confirms that UTI is a common complication in patients with T2DM. Patients with T2DM who have had previous infections, who are older, and who are male, as well as patients who have more comorbidities or severe renal insufficiency, face above-average UTI treatment costs. These patient groups, therefore, should receive special attention in the real-world treatment of T2DM, which should include a regular screening of UTI risk.

Mueller S, Agostini H, Ehlken Ch, Bauer-Steinhusen U, Hasanbasic Z, Wilke T.  Patient Preferences in the Treatment of Neovascular Age-Related Macular Degeneration. Ophthalmology.DOI:http://dx.doi.org/10.1016/j.ophtha.2015.12.001

Abstract

Purpose

The objective of our study was to investigate preferences of patients with neovascular age-related macular degeneration (nAMD) for different anti-vascular endothelial growth factor (VEGF) treatment schemes.

Design

We used a discrete choice experiment (DCE) design as part of a telephone interview.

Participants

Patients with nAMD aged at least 50 years were included in the study.

Methods

Telephone interviews were done between November 2012 and October 2013.

Main Outcome Measures

In our DCE survey, we measured patient preferences toward specific levels of attributes that describe different options in the everyday intravitreal injection treatment setting: (1) treatment scheme; (2) change of visual acuity (VA); and (3) time the patient needs for each visit to the eye specialist.

Results

A total of 284 patients with nAMD with a mean age of 77.4±7.1 years (women: 59.9%) completed the DCE interviews. Of them, 22.9% had poor VA at study inclusion, 54.9% had moderate VA, and 14.1% had good VA; VA was not available for 8.1% of the patients. Generally, patients preferred the attribute levels “improvement in VA” and “short time per specialist visit.” The results for the attribute “treatment scheme” were inconclusive because none of the attribute levels (injections every 4 weeks, every 8 weeks, and pro re nata) were associated with statistically significant utility differences. This also mirrors the relative importance of the different attributes in patient decisions: “Change of VA” influenced decision making for a treatment option in 73.6% of cases; “waiting, treatment, and travel time” influenced decision making in 21.0% of cases; and “treatment scheme” influenced decision making for a treatment option in 5.4% of cases. To obtain improved VA instead of a worsening VA, patients in our study stated to be willing to accept a very long time needed per physician visit of 21.2 hours (8.5 hours for improved rather than stable VA and 12.7 hours for stable VA rather than worsening VA).

Conclusions

To prevent deterioration of VA, patients with nAMD seem to be willing to accept a high treatment burden with regular intravitreal injections at short intervals and long periods of waiting, treatment, and traveling for their consultations.