Therapy In Germany Research Articles

Contemporary treatment of metastatic clear cell renal cell carcinoma

Renal cell carcinoma is one of the mostcommon malignant tumors in Germany with an increasing incidence. Drug therapy is indicated in relapsed or metastatic disease. The article is based on the content of the recent guidelines and aselective literature search. Combination therapies based on acheckpoint inhibitor are the current standard in first-line treatment of metastatic renal cell carcinoma. The median overall survival could thus be extended to > 50months. The International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) score is used for risk classification. When selecting asuitable combination therapy, it is important to consider the advantages and disadvantages for each individual patient. There is currently no standard for follow-up therapies. So far, combination therapies have not shown any significant advantage in second-line treatment. It is recommended to switch to asubstance that has not yet been used. Currently, one purely immuno-oncology combination and four combinations of one immune checkpoint inhibitor and one tyrosine kinase inhibitor (TKI) are approved for first-line therapy in Germany. The added value of further intensification of therapy, in particular through triple combinations or further combination therapy in the second line, has not yet been proven.

National trends of left ventricular assist device therapy in Germany

Abstract Background The prevalence of advanced heart failure (HF) is increasing and prognosis remains poor. Although heart transplantation is still considered to be the gold standard for the treatment of advanced HF in selected patients, its use is limited by organ donor shortage and a growing burden of cormorbidities among potential recipients. The 2021 European Society of Cardiology (ESC) guidelines recommend consideration of long-term mechanical circulatory support with a left ventricular assist device (LVAD) in eligible patients with advanced heart failure (HF) who are refractory to medical/device therapy. Purpose The purpose of this study was to evaluate the national trends of LVAD in Germany. The main hypothesis was that LVAD therapy is still underutilized. Methods From the national database of the German Federal Statistical Office (DESTATIS), we identified all patients who underwent LVAD implantation in Germany between January 2011 and December 2022 (n = 9,232). We compared temporal trends and in-hospital outcomes. Results From 2011 to 2022, number of LVAD implantation was highest in the year 2017 (n = 914) and steadily decreased over the following years (2022: n = 617). Mean age of LVAD recipients was 56.2 years (2011-2015) and increased to 58.4 years (2020-2022). The majority of LVAD recipients are male (84,8 %), and this trend has been stable during the entire time period. In-hospital mortality after LVAD remains high, but has been decreasing (25.8% during 2011-2015 compared to 20.2% during 2020-2022). Conclusion Although LVAD is recommended in eligible patients with advanced HF, our study suggests an underutilization of LVAD in this patient population and especially in female patients.

Medication Burden Before and After Prescription of Biologics in Patients with Inflammatory Bowel Disease.

Background: Biologics are a cornerstone in the treatment of severe cases of inflammatory bowel disease (IBD) and aim to control the disease and improve quality of life. This study investigated changes in nonbiologic medication prescriptions for IBD patients initiating biologic therapy in Germany. Methods: This study used data from anonymized pharmacy records in the German longitudinal prescription (LRx) database and included biologic-naive IBD patients who received their first biologic therapy prescription between 2016 and 2022. Changes in prescription rates and pill counts for nonbiologic medications (corticosteroids, 5-aminosalicylates (5-ASA), proton pump inhibitors, analgesics, immunosuppressants, Vitamin D, iron, and antibiotics) before and after the initiation of biologic therapy were assessed using descriptive statistics, McNemar's tests, and Poisson regression models, adjusting for age and sex. Results: A total of 29,559 biologic-naive IBD patients were included. Prior to index, 91.2% received at least one nonbiologic medication prescription, where corticosteroids and 5-ASA were the most common. Postindex, the overall prescription rate decreased to 87.7%, with significant reductions in prescriptions observed for corticosteroids, 5-ASA, and immunosuppressants (p-values < 0.001). The mean (SD) pill count dropped from 704 (1712) to 514 (1651), with the largest mean differences (95% CI) having been for corticosteroids (-77.9 [-80.3 to -75.5]), 5-ASA (-61.6 [-65.2 to -58.1]), and immunosuppressants (-55.0 [-57.5 to -52.6]). Older patients tended to have greater decreases in pill counts for corticosteroids and 5-ASA, while males showed statistically significant reductions in pill count for immunosuppressants compared with females. Conclusions: This study demonstrates that the prescription of nonbiologic medications significantly decreased after biologic therapy initiation. The use of biologics may therefore lead to improved disease management and potentially better patient outcomes.

Amelioration of suicidal ideation in routine care psychotherapy: Preliminary findings from a large multicenter assessment

BackgroundSuicidal ideation represents a major concern in clinical practice. Yet, little is known about the effects of routine psychotherapy on the amelioration of suicidal ideation. Therefore, the aim of the current study is to assess mental disorder-specific changes of suicidal ideation in a large sample of adult outpatients undergoing routine-care cognitive-behavioural therapy in Germany. MethodsA total of N = 4549 adult outpatients, 64.2% female; age: M(SD) = 36.83 (14.03), range: 18–89 years of age, who completed cognitive-behavioral therapy at one of 26 outpatient clinics in Germany were included in the current study. Amelioration of suicidal ideation was assessed using the Suicide Item (Item 9) of the Beck-Depression Inventory. ResultsSuicidal ideation was reported by 36.7% of the patients pretreatment and by 17.6% posttreatment. Effect sizes were small to moderate (d = 0.25 -0.51) and 4.4% reported an increase in suicidal ideation. Residual suicidal ideation at the posttreatment assessment was more likely in patients diagnosed with recurrent Major Depression, Dystymia, and Borderline Personality Disorder, and older patients. LimitationThe study relies on a naturalistic sample, no waitlist or control conditions were involved. ConclusionAcross primary diagnoses, a significant proportion of patients experience an amelioration of suicidal ideation over the course of routine-care psychotherapy. Still, a substantial proportion of patients report no change or an increase in suicidal ideation during treatment. Thus, continuous monitoring of suicidal ideation appears to be imperative throughout the psychotherapeutic process.

The German cochlear implant registry: one year experience and first results on demographic data

PurposeClinical registries have great potential for quality control of medical procedures regarding the indications, therapeutic processes and results, including their possible complications. This is particularly true when providing patients with severe hearing loss or deafness with a cochlear implant (CI). This treatment represents a lifelong care process that requires continuous quality control over time. On the initiative of the Executive Committee of the German Society of Otorhinolaryngology (Deutsche Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie e.V., DGHNO-KHC), a national German CI registry (Deutsches Cochlear Implant Register, DCIR) was established in January 2022. This article focuses on the first demographic and baseline data of the DCIR.MethodsThe DCIR covers the complete therapeutic process from indication, surgery, fitting and lifelong aftercare in CI therapy. By the end of 2022, 75 hospitals in Germany had agreed to contribute to the DCIR.ResultsDuring the year 2022, 63 hospitals actively contributed data to the DCIR. Pseudonymized data from 2,292 CI implantations (2,176 primary implantations, 99 explantations with immediate re-implantations and 17 re-implantations following an earlier explantation) in 2,108 patients were documented. Cochlear implantation was accomplished in 1,807 adults (≥ 18 years) and 301 children (< 18 years). Fourty patients (1,9%) were children < 1 year of age and 55 (2,6%) were patients > 85 years. From the total of 2,292 implantations, 226 (9.9%) were performed as simultaneous bilateral implantations (CI implantation in both ears of 113 patients on the same day of surgery) and 412 implantations (19.1% of 2,162 implantations with data provided on the contralateral ear’s hearing status) were in patients with single sided deafness (normal hearing in the contralateral ear). In addition, the reported complications in 2022 were also evaluated. Seven reports (0.4%) of mild to moderate severe facial nerve dysfunctions were documented. No reports of severe or total facial nerve dysfunction (House-Brackmann grade V/VI), meningitis or death related to CI therapy were documented.ConclusionAlthough still in the start-up phase, these initial DCIR data already provide an interesting first insight into the demographic structure and baseline data of CI therapy in Germany. The successful implementation of the DCIR represents an important step towards continuous quality control of CI care.

A decade of chronic lymphocytic leukaemia therapy in Germany: Real-world treatment patterns and outcomes (2010-2022).

Pharmacotherapy options for chronic lymphocytic leukaemia (CLL) have expanded significantly in recent years. These options include chemotherapy, chemoimmunotherapy and signalling pathway inhibitors. A notable shift in the treatment landscape began with the widespread adoption of ibrutinib in 2016. This analysis of claims data focuses on understanding how the use of novel therapies has evolved in clinical practice over the past decade in Germany. Anonymized claims data (2010-2022) from German statutory health insurance was used, covering patient demographics, treatments, and prescriptions. The study population included patients with two confirmed CLL diagnoses. Treatment patterns were analysed, and survival outcomes were compared using time-to-event analyses. In the analysed cohort of 2983 incident CLL patients, 1041 started first-line therapy between 2011 and 2022, with a median duration of 18 months from diagnosis to the first prescription. Chemoimmunotherapy, the predominant 1L therapy until 2019, decreased significantly, while targeted therapy usage increased from 3% in 2015 to 77% in 2022. Targeted therapies became dominant in patients receiving treatment for relapsed or refractory disease after 2016. Median treatment durations were: 122 days for chemo, 176 days for chemo-immuno, and 373 days for targeted therapy. The overall survival for patients diagnosed in or after 2016 was significantly better (hazard ratio 0.56, 95% confidence interval, 0.44-0.69)). The adoption of targeted therapies like ibrutinib and venetoclax has transformed CLL treatment in Germany, leading to improved patient outcomes. Additionally, we demonstrate successful adherence to evolving clinical guidelines.

History of cardiac pacemaker therapy in Germany

Cardiac pacemaker therapy began with successful stimulation of human hearts already in the first half of the 20thcentury. Complete implantation of apacemaker by the cardiac surgeon Åke Senning on October 8, 1958 at the Karolinska Hospital in Stockholm is considered the actual birth of today's pacemaker therapy. The first pacemaker implantation in Germany was performed by Hans-Joachim Sykosch on October 6, 1961 at the Surgical Clinic of the University of Düsseldorf. Two years later, the first implantation in East Germany (GDR) was carried out by Friedrich Flemming on September 2, 1963 at the Charité in East Berlin. The first pacemaker manufactured in West Germany arrived on the market 1963; East Germany started device production in 1978. In 1974, pacemaker therapy in West Germany showed a50% survival rate after 6.3years compared to < 1year with drug therapy. After initially using bare metal wires, pacemaker leads have significantly improved in both quality and reliability. Development culminated in the leadless pacemaker. Battery development led to avariety of inventions: rechargeable pacemakers, biogalvanic cells, bioenergy sources, nuclear generators and lithium batteries, the latter ultimately prevailed. In the beginning, only fixed-rate ventricular pacemakers were available. Subsequently, systems adapted to physiological requirements were developed: on-demand pacemakers, atrial-based pacing and rate-adaptive systems. However, it was not until the return to direct stimulation of the conduction system that truly physiological stimulation of the heart became possible.

Acquisition, status and transfer of knowledge in compression therapy : Cross-sectional study in healthcare professions using phlebological compression therapy

Due to scientific progress, healthcare professionals should regularly undergo appropriate continuing education. For this, knowledge transfer is essential. Therefore, the aim of this cross-sectional study was to investigate the acquisition, status and transfer of knowledge of professional groups applying phlebological compression therapy in Germany. Healthcare professionals (physicians, nurses and medical assistants) received aquestionnaire developed for this study, which queried different aspects of acquisition, status and transfer of knowledge. Responses from 522 participants were analysed. The topic of compression therapy was not taught in the nursing or medical education of 43.3%. Specialist journals that address compression therapy were read regularly (at least 6times/year) by 16.1% of the participants; 63.0% had no specialist books on this subject. Only 6.7% were aware of AWMF ("Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften") guidelines on the topic and 16.3% of the corresponding DNQP ("Deutsches Netzwerk für Qualitätsentwicklung in der Pflege") expert standard. In all, 41.2% participated in at least one internal training on compression therapy per year, 72.0% in external training and 19.2% in online training. Atotal of 30.7% stated that they did not use any information sources to acquire knowledge. Possible sources of knowledge about compression therapy in Germany are insufficiently known within the investigated healthcare professional groups studied or are not regularly used. The result is aconsiderable knowledge deficit with adiscrepancy between the current state of science and practice.

Management of Patients Undergoing CAR-T Cell Therapy in Germany

Introduction: Chimeric antigen receptor positive T cell (CAR-T cell) treatment became standard therapy for relapsed or refractory hematologic malignancies, such as non-Hodgkin’s lymphoma and multiple myeloma. Owing to the rapidly progressing field of CAR-T cell therapy and the lack of generally accepted treatment guidelines, we hypothesized significant differences between centers in the prevention, diagnosis, and management of short- and long-term complications. Methods: To capture the current CAR-T cell management among German centers to determine the medical need and specific areas for future clinical research, the DAG-HSZT (Deutsche Arbeitsgemeinschaft für Hämatopoetische Stammzelltransplantation und Zelluläre Therapie; German Working Group for Hematopoietic Stem Cell Transplantation and Cellular Therapy) performed a survey among 26 German CAR-T cell centers. Results: We received answers from 17 centers (65%). The survey documents the relevance of evidence in the CAR-T cell field with a homogeneity of practice in areas with existing clinical evidence. In contrast, in areas with no – or low quality – clinical evidence, we identified significant variety in management in between the centers: management of cytokine release syndrome, immune effector cell-related neurotoxicity syndrome, IgG substitution, autologous stem cell backups, anti-infective prophylaxis, and vaccinations. Conclusion: The results indicate the urgent need for better harmonization of supportive care in CAR-T cell therapies including clinical research to improve clinical outcome.

Long-acting prescriptions and therapy for HIV-1 from market launch to the present in Germany (May 2021 to December 2023).

In Europe, the combination of cabotegravir (CAB) with rilpivirine (RPV) has been approved as a dual injection long-acting (LA) therapy for the treatment of human immunodeficiency virus type 1 (HIV-1) infections in adults since December 2020. Studies have shown that between 36 and 61% of people living with HIV (PLWHIV) prefer LA therapy. However, there are no real-world data on the number of people receiving LA therapy, in Germany or internationally. The aim of this study was to assess the current situation and trends in usage of LA therapy for the treatment of HIV-1 in Germany. Based on pharmacy prescription data derived from Insight Health, the monthly number of prescriptions for oral CAB, CAB-LA, and RPV-LA over the entire period of availability in Germany was analyzed and evaluated (May 2021 to December 2023). The number of 1st and 2nd initiation injections and subsequent maintenance injections was calculated on the basis of the prescriptions for oral CAB initiation. The bimonthly schedule resulted in two growing cohorts from September 2021 with an estimated 14,523 CAB-LA prescriptions over the entire period. Accordingly, in December 2023, there were approximately 1,364 PLWHIV receiving LA therapy, of whom 1,318 were receiving maintenance therapy. Only treatments with bimonthly regimens were carried out. Accounting for people not covered by statutory health insurance (~13%), a total of ~1,600 PLWHIV were receiving LA therapy in Germany in December 2023. The average rounded annual cost of therapy in 2023 was €11,940 (maintenance therapy with initiation) and €10,950 (maintenance therapy without initiation). To our knowledge, this is the first study of real-world use and number of people receiving LA therapy. A strength of our study is the nearly complete coverage of people with statutory health insurance in Germany. The predicted demand for LA therapy does not match the actual number of people receiving LA therapy. Although the number of PLWHIV receiving LA therapy increased steadily, they accounted for just under 2% of the estimated total number of people receiving HIV therapy in Germany in 2023, almost 2 years after the market launch. No significant increase in prescriptions is expected; on the contrary, the trend is leveling off and is unlikely to change drastically in the near future. Hence, the need for this mode of therapy in Germany appears to be limited. Follow-up studies at regular intervals on the further course would be useful and are recommended, as well as investigations into the possible reasons for the slow uptake to inform public health experts and possibly broaden treatment options.

Management of acute appendicitis during COVID-19 pandemic. Single center data from a tertiary care hospital in Germany.

The unexpected global overload of the health system during COVID-19 pandemic has caused changes inmanagement of acute appendicitis worldwide. Whereas conservative treatment was widely recommended, the appendicectomy remained standard therapy in Germany. We aimed to investigate the impact of COVID-19 pandemic ontreatment routine for acute appendicitis at University Hospital of Magdeburg. Adult patients with clinical and/or radiological diagnosis of acute appendicitis were included in the single center retrospective study. Data was collected to patient demographics, treatment modality and outcomes including morbidity and length of stay. The patient data related to COVID-19 period from March 22, 2020 to December 31, 2021 (649days) were compared to the Non-COVID-19 period from June 12, 2018 to March 21, 2020 (649days). Subgroup analysis related to conservative or surgical treatment has been performed. A total of 385 patients was included in the study, 203 (52.73%) during Non-COVID-19 period and 182 (47.27%) during COVID-19 period. Mean age of entire collective was43.28 years, containing 43.9% female patients (p=0.095). Conservative treatment was accomplished in 49 patients (12.7% of entire collective), increasing from 9.9 % to 15.9% during COVID-19 period (p=0.074). Laparoscopic appendicectomy was performed in 99.3% (n=152) of operated patients during COVID-19 period (p=0.013), followed by less postoperative complications compared to reference period (23.5% vs. 13.1%, p=0.015). The initiation of antibiotic therapy after the diagnosis increased from 37.9 % to 53.3% (p=0.002) during COVID-19 period regardless the following treatment modality. Antibiotic treatment showed shorter duration during pandemic period (5.57days vs. 3.16days, p<0.001) and it was given longer in the conservative treatment group (5.63days vs. 4.26days, p=0.02). The overall length of stay was shorter during COVID-19 period (4.67days vs. 4.12 days, p=0.052) and in the conservative treatment group (3.08days vs. 4.47days, p<0.001). However, the overall morbidity was lower during the COVID-19 period than before (17.2% vs. 7.7%, p=0.005) and for conservative therapy compared toappendicectomy (2 % vs. 14.3%, p=0.016). There was no mortality documented. According to our findings the COVID-19 pandemic had a relevant impact on treatment of acute appendicitis, but it was possible to maintain the traditional diagnostic and treatment pathway. Although laparoscopic appendicectomy remains a recommended procedure, the conservative treatment of uncomplicated appendicitis with excellent short-term outcome can be a safe alternative to surgery during potential new wave of COVID-19 pandemic and in the daily routine.

Narcissistic dimensions and depressive symptoms in patients across mental disorders in cognitive behavioural therapy and in psychoanalytic interactional therapy in Germany: a prospective cohort study

Narcissistic personality traits have been theorised to negatively affect depressive symptoms, therapeutic alliance, and treatment outcome, even in the absence of narcissistic personality disorder. We aimed to examine how the dimensional narcissistic facets of admiration and rivalry affect depressive symptoms across treatment modalities in two transdiagnostic samples. We did a naturalistic, observational prospective cohort study in two independent adult samples in Germany: one sample pooled from an inpatient psychiatric clinic and an outpatient treatment service offering cognitive behavioural treatment (CBT), and one sample from an inpatient clinic providing psychoanalytic interactional therapy (PIT). Inpatients treated with CBT had an affective or psychotic disorder. For the other two sites, data from all service users were collected. We examined the effect of core narcissism and its facets admiration and rivalry, measured by Narcissistic Admiration and Rivalry Questionnaire-short version, on depressive symptoms, measured by Beck's Depression Inventory and Patient Health Questionnaire-Depression Scale, at baseline and after treatment in patients treated with CBT and PIT. Primary analyses were regression models, predicting baseline and post-treatment depression severity from core narcissism and its facets. Mediation analysis was done in the outpatient CBT group for the effect of the therapeutic alliance on the association between narcissism and depression severity after treatment. The sample included 2371 patients (1423 [60·0%] female and 948 [40·0%] male; mean age 33·13 years [SD 13·19; range 18-81), with 517 inpatients and 1052 outpatients in the CBT group, and 802 inpatients in the PIT group. Ethnicity data were not collected. Mean treatment duration was 300 days (SD 319) for CBT and 67 days (SD 26) for PIT. Core narcissism did not predict depression severity before treatment in either group, but narcissistic rivalry was associated with higher depressive symptom load at baseline (β 2·47 [95% CI 1·78 to 3·12] for CBT and 1·05 [0·54 to 1·55] for PIT) and narcissistic admiration showed the opposite effect (-2·02 [-2·62 to -1·41] for CBT and -0·64 [-1·11 to -0·17] for PIT). Poorer treatment response was predicted by core narcissism (β 0·79 [0·10 to 1·47]) and narcissistic rivalry (0·89 [0·19 to 1·58]) in CBT, whereas admiration showed no effect. No effect of narcissism on treatment outcome was discernible in PIT. Therapeutic alliance mediated the effect of narcissism on post-treatment depression severity in the outpatient CBT sample. As narcissism affects depression severity before and after treatment with CBT across psychiatric disorders, even in the absence of narcissistic personality disorder, the inclusion of dimensional assessments of narcissism should be considered in future research and clinical routines. The relevance of the therapeutic alliance and therapeutic strategy could be used to guide treatment approaches. IZKF Münster. For the German translation of the abstract see Supplementary Materials section.

Retrospective real-world analysis of adherence and persistence to lipid-lowering therapy in Germany

BackgroundCardiovascular disease is the leading cause of mortality in Germany. Cardiovascular risk can be mitigated with long-term lipid-lowering therapies (LLTs) that reduce levels of low-density lipoprotein cholesterol. Although effective, risk mitigation is hindered by poor persistence and adherence.ObjectiveTo investigate real-world persistence and adherence to LLTs through 36 months post-initiation.MethodsThis retrospective cohort study included patients with dyslipidemia who were newly prescribed LLTs between July and December 2017, using anonymized prescription data from the Insight Health™ Patient Insight Tool, and followed up until March 2021. Persistence and adherence to the therapies were stratified by age and sex. The proportion of days covered (PDC) was used to measure adherence.ResultsPatients with dyslipidemia and newly prescribed statins (n = 865,732), ezetimibe (n = 34,490), or anti-proprotein convertase subtilisin/kexin type 9 monoclonal antibodies (anti-PCSK9 mAbs; n = 1940) were included. Persistence to LLTs declined gradually across all treatment subgroups and was lower in women than men. Adherence, calculated as the mean PDC at the end of the analysis period (July 2017‒March 2021) was 0.84, 0.92, and 0.93 for statins, ezetimibe, and anti-PCSK9 mAbs, respectively. Among patients who discontinued treatment, mean treatment duration was 265, 255, and 387 days for statins, ezetimibe, and anti-PCSK9 mAbs, respectively. Only ~ 10% of patients persisted between 201 and 300 days. By Day 300, 71% of patients on statins had discontinued treatment. At 36 months, overall persistence rates were lowest with statins (20.6%), followed by ezetimibe (22.3%) and anti-PCSK9 mAbs (50.9%).ConclusionsHigh non-persistence rates were observed across all LLT regimens analyzed, with the lowest persistence rates observed with statins.Graphical

Evolving trends in the surgical therapy of patients with endometrial cancer in Germany: analysis of a nationwide registry with special emphasis on perioperative outcomes.

Endometrial cancer (EC) is the most common gynecological malignancy in women, with increasing incidence in the last decades. Surgical therapy is the mainstay of the initial management. The present study analyzed the evolving trends of surgical therapy in Germany in patients diagnosed with EC recorded in a nationwide registry. All patients with the diagnosis of EC undergoing open surgery, laparoscopic surgery, and robotic-assisted laparoscopic surgery between 2007 and 2018 were identified by international classification of diseases (ICD) or specific operational codes (OPS) within the database of the German federal bureau of statistics. A total of 85,204 patients underwent surgical therapy for EC. Beginning with 2013, minimal-invasive surgical therapy was the leading approach for patients with EC. Open surgery was associated with a higher risk of in-hospital mortality (1.3% vs. 0.2%, p < 0.001), of prolonged mechanical ventilation (1.3% vs. 0.2%, p < 0.001), and of prolonged hospital stay (13.7 ± 10.2days vs. 7.2 ± 5.3days, p < 0.001) compared to laparoscopic surgery. A total of 1551 (0.04%) patients undergoing laparoscopic surgery were converted to laparotomy. Procedure costs were highest for laparotomy, followed by robotic-assisted laparoscopy and laparoscopy (8286 ± 7533€ vs. 7083 ± 3893€ vs. 6047 ± 3509€, p < 0.001). The present study revealed that minimal-invasive surgery has increasingly become the standard surgical procedure for patients with EC in Germany. Furthermore, minimal-invasive surgery had superior in-hospital outcomes compared to laparotomy. Moreover, the use of robotic-assisted laparoscopic surgery is increasing, with a comparable in-hospital safety profile to conventional laparoscopy.

Persistence with first-line antihypertensive therapy in Germany: A retrospective cohort study with 2,801,469 patients.

The goal of this retrospective cohort study was to investigate 3-year persistence with antihypertensive drug therapy and the association between antihypertensive drug classes and therapy discontinuation risk in Germany. The present retrospective cohort study was based on the IQVIA longitudinal prescription database (LRx) and included adult outpatients (≥18 years) with an initial prescription of antihypertensive monotherapy alone including diuretics (DIU), β-blockers (BB), calcium channel blockers (CCB), ACE inhibitors (ACEi), and angiotensin II receptor blockers (ARB) in Germany between January 2017 and December 2019 (index date). A Cox proportional hazards regression model was also used to assess the relationship between antihypertensive drug classes and non-persistence adjusted for age and sex. This study included 2,801,469 patients. Patients on ARB monotherapy exhibited the highest persistence within 1 year (39.4%) and 3 years (21.7%) after the index date. Patients on DIU monotherapy showed the lowest persistence (16.5% after 1 year, 6.2% 3 years after the index date). In the overall population, initial monotherapy with DIU (HR: 1.48) was positively associated with monotherapy discontinuation, whereas ARB monotherapy was (HR=0.74) negatively associated with monotherapy discontinuation compared to BB. However, in the age group >80, there was a slight negative association between DIU intake and monotherapy discontinuation (HR=0.91). This large cohort study reveals significant differences in 3-year persistence with antihypertensives, which were strongest for ARB and weakest for DIU. However, the differences also depended on age, with much better DIU persistence in the elderly.

Phage Therapy in Germany-Update 2023.

Bacteriophage therapy holds promise in addressing the antibiotic-resistance crisis, globally and in Germany. Here, we provide an overview of the current situation (2023) of applied phage therapy and supporting research in Germany. The authors, an interdisciplinary group working on patient-focused bacteriophage research, addressed phage production, phage banks, susceptibility testing, clinical application, ongoing translational research, the regulatory situation, and the network structure in Germany. They identified critical shortcomings including the lack of clinical trials, a paucity of appropriate regulation and a shortage of phages for clinical use. Phage therapy is currently being applied to a limited number of patients as individual treatment trials. There is presently only one site in Germany for large-scale good-manufacturing-practice (GMP) phage production, and one clinic carrying out permission-free production of medicinal products. Several phage banks exist, but due to varying institutional policies, exchange among them is limited. The number of phage research projects has remarkably increased in recent years, some of which are part of structured networks. There is a demand for the expansion of production capacities with defined quality standards, a structured registry of all treated patients and clear therapeutic guidelines. Furthermore, the medical field is still poorly informed about phage therapy. The current status of non-approval, however, may also be regarded as advantageous, as insufficiently restricted use of phage therapy without adequate scientific evidence for effectiveness and safety must be prevented. In close coordination with the regulatory authorities, it seems sensible to first allow some centers to treat patients following the Belgian model. There is an urgent need for targeted networking and funding, particularly of translational research, to help advance the clinical application of phages.

Disease characteristics and clinical practice of BRAF V600E-mutant metastatic colorectal cancer treatment: Baseline analysis of patients enrolled in the BERING CRC study.

34 Background: BRAF V600E-mutant metastatic colorectal cancer (mCRC) is associated with a poor prognosis and limited clinical data. Based on results from the BEACON CRC trial, targeted treatment with encorafenib plus cetuximab (E+C) is available as a standard of care for these patients (pts) after prior systemic therapy. Since data from controlled clinical trials are based on a selected patient population, the non-interventional study (NIS) BERING CRC observes a broader patient population in clinical practice. Methods: BERING CRC is the first NIS investigating the use of E+C in clinical practice of BRAF V600E-mutant mCRC treatment after prior systemic therapy in Germany, Austria, and Switzerland. For the present analysis, disease characteristics and treatment data of the initial 81 pts were documented in 44 sites across Germany and Austria between 09/2020 and 04/2022. BERING-CRC is ongoing and aims to enroll up to 300 pts from 126 German, Austrian, and Swiss sites. The study observes pts treated according to the approved respective Summary of Product Characteristics (SmPC). The primary endpoint is the 1-year overall survival rate. Secondary endpoints include efficacy, QoL, and tolerability of E+C. Results: 81 pts were included in this baseline analysis. Median age was 67 years (range 34-88) and 48% were female. 48 pts (59%) were documented with right-sided tumors and for 62% stage IV disease was noted at initial diagnosis. In the metastatic setting, main sites of metastasis were liver, peritoneum, and lung (52%, 32%, and 22% of pts, respectively), with 16% of pts having ≥ 3 sites documented. For 30% of pts, an ECOG performance status (PS) of 0 was documented at baseline assessment (57% ECOG PS 1 or 2). Adjuvant treatment was reported for 22 pts while relapse ≤ 6 months was documented for 10 of them. Consistent with BEACON CRC, adjuvant systemic therapy with relapse within ≤6 months was counted as metastatic 1st line treatment. 91% of pts with adjuvant treatment received chemotherapy alone in this setting. 4 pts (5%) were documented with E+C treatment directly following adjuvant therapy and 55% of all pts with documented first-line treatment (69 pts) received chemotherapy alone (CT), for 35% chemotherapy was combined with targeted therapy (CT+TT), 3% received immunotherapy, and 1% received TT alone. In second-line, 71% of pts with documented treatment received E+C (7% CT, 16% CT+TT). An initial bi-weekly cetuximab dosing was reported for 10% of pts treated with E+C. Conclusions: While the high number of pts with right-sided tumors was in line with previous findings on BRAF V600E-mutant mCRC pts, synchronous metastasis was reported considerably more often in this real-world cohort. As complementation to previous controlled clinical trial data, pts enrolled in BERING-CRC were notably older and presented with higher ECOG PS compared to the pivotal study. Clinical trial information: NCT04673955 .

Challenges and Solutions for the Benefit Assessment of Tumor-Agnostic Therapies in Germany

ObjectivesPrecision medicine is increasingly important in cancer treatment. Tumor-agnostic therapies are used regardless of tumor entity because they target specific biomarkers in tumors. In Germany, the benefit assessment of oncological pharmaceuticals has traditionally been entity specific. Thus, the assessment of tumor-agnostic therapies leaves stakeholders with various challenges. Our aim was to systematically identify challenges and possible solutions for the benefit assessment of therapies in tumor-agnostic indications using a 2-step sequential qualitative approach. MethodsTo identify relevant challenges, we conducted qualitative interviews with different stakeholders who were involved in previous benefit assessments of tumor-agnostic therapies in Germany. To identify possible solutions for these challenges, we systematically searched MEDLINE, Embase, and the websites of European health technology assessment bodies for relevant literature. ResultsWe identified 9 categories of challenges of which the following were deemed particularly relevant: the absence of direct comparative studies, challenges regarding the use of basket studies and indirect comparisons, challenges in determining the appropriate comparative therapy in a tumor-agnostic indication, and challenges on the system side. Seven categories of solutions were identified, including an increased use of real-world evidence, making conditional decisions in the context of systematic reassessments, splitting the field of application, and finding (new) ways to design and analyze basket studies. ConclusionA range of possible solutions, which can help to meet the identified challenges in Germany, have been found. Future research should investigate the acceptance and feasibility of these solutions.

HTA177 Current Developments in the Market Access Conditions for Gene Therapies in Germany

Gene therapies (GT) are highly innovative medicinal products which have the potential to heal patients from a life-threatening disease with a single application. In this work, we aim to give an overview on the benefit assessment of those GT currently available on the German market. In addition, we intend to give first insights regarding the new instrument of routine practice data collection and evaluation (anwendungsbegleitende Datenerhebung, AbD), which can be imposed by the Federal Joint Committee (G-BA) to evaluate innovative medicines.

EE144 APAP and Telemonitoring for Initiation and Follow-up of OSA Therapy in Germany: Economic and Environmental Evaluation

EE144 APAP and Telemonitoring for Initiation and Follow-up of OSA Therapy in Germany: Economic and Environmental Evaluation