Real-World Safety, Effectiveness, and Patient-Reported Outcomes in Patients with Chronic Hepatitis C Virus Infection Treated with Glecaprevir/Pibrentasvir: Updated Data from the German Hepatitis C-Registry (DHC-R).

Using data from the German Hepatitis C-Registry (Deutsche Hepatitis C-Register, DHC-R), we report the real-world safety and effectiveness of glecaprevir/pibrentasvir (GLE/PIB) treatment and its impact on patient-reported outcomes (PROs) in underserved populations who are not typically included in clinical trials, yet who will be crucial for achieving hepatitis C virus (HCV) elimination. The DHC-R is an ongoing, non-interventional, multicenter, prospective, observational cohort study on patients treated for chronic HCV infection in Germany. The data cutoff was 17 January 2021. The primary effectiveness endpoint was sustained virologic response at post-treatment Week 12 (SVR12). Safety outcomes were assessed in all patients receiving GLE/PIB. PROs were assessed using the SF-36 survey. Of 2354 patients, 1964 had valid SVR12 data (intention-to-treat analysis). Of these, 1905 (97.0%) achieved SVR12 with rates similar across the comorbidities analyzed, except for people who actively use drugs (PWUD (active)) (86.4%). Excluding those who discontinued treatment and did not achieve SVR12, or were reinfected with HCV, the rate was 99.3%, with similar results regardless of comorbidity. PWUD (active) and those with psychiatric disorders had the most meaningful improvements in PROs. Adverse events (AEs) occurred in 631/2354 patients (26.8%), and serious AEs in 44 patients (1.9%). GLE/PIB was highly effective and well tolerated in this real-world study of patient groups key to HCV elimination.

The changing characteristics of patients infected with chronic hepatitis C virus from 2014 to 2019: Real-world data from the German Hepatitis C-Registry (DHC-R).

The number of patients diagnosed with hepatitis C virus (HCV) is markedly higher than the number initiating treatment indicating gaps in the care cascade, likely centred around reaching at-risk populations. Understanding changing characteristics of patients with HCV allows for targeted programs that increase linkage to care. We investigated changes in demographic and clinical characteristics of patients registered in the German Hepatitis C-Registry (DHC-R) from 1 January 2014 to 31 December 2019. The DHC-R is an ongoing, noninterventional, multicentre, prospective, observational cohort registry including 327 German centres. Patient characteristics were analysed over time in 7 phases for all patients completing a screening visit. Overall, 14,357 patients were enrolled. The percentage of treatment-naïve/non-cirrhotic patients increased from 34.4% in phase 1 (1 January-31 December 2014) to 68.2% in phase 7 (1 August-31 December 2019). The proportion of migrants, alcohol users, people who inject drugs, and those receiving opiate substitution therapy increased in later registry phases. Most patients (60.1%) were receiving comedication at baseline. The most prescribed comedications were drugs used to treat opioid dependence which increased from 9.2% in phase 1 to 24.0% in phase 7. The patients' mean age decreased from 52.3 years in phase 1 to 48.7 years in phase 7. From 2014 to 2019, the proportion of at-risk patients enrolling in the registry increased. To eliminate viral hepatitis as a major public health threat, a continued commitment to engaging underserved populations into the HCV care cascade is needed.

Hepatitis C virus: Current steps toward elimination in Germany and barriers to reaching the 2030 goal.

Hepatitis C virus (HCV) affects over 70 million people globally, with an estimated 399 000 HCV-related deaths in 2016. The World Health Organization (WHO) has set a goal to eliminate HCV by 2030. Despite the availability of direct-acting antivirals-highly effective and well-tolerated therapies for HCV-many patients infected with HCV in Germany have not initiated treatment, including a majority of those who are aware of their positive diagnosis. Barriers to screening, diagnosis, and treatment are major factors taking many countries off track for HCV elimination by 2030. Identifying country-specific barriers and challenges, particularly in at-risk populations such as people who inject drugs or men who have sex with men, has the potential to create tailored programs and strategies to increase access to screening or treatment and engage at-risk populations. This review aims to report the current steps toward HCV elimination in Germany, the country-specific barriers and challenges that will potentially prevent reaching the 2030 HCV elimination goal and describe good practice examples to overcome these barriers.

Glecaprevir/pibrentasvir for 8 weeks in patients with compensated cirrhosis: Safety and effectiveness data from the German Hepatitis C-Registry.

Glecaprevir/pibrentasvir, a pangenotypic, direct-acting antiviral combination approved for chronic hepatitis C virus treatment, has limited real-world evidence supporting 8-week therapy in compensated cirrhosis. We investigated effectiveness and safety of 187 hepatitis C virus-infected, treatment-naïve, patients with compensated cirrhosis receiving 8-week glecaprevir/pibrentasvir therapy in the German Hepatitis C-Registry between 2 August 2017 and 1 January 2020. Sustained virologic response was 98.4% (127/129) in the per-protocol analysis (excluding patients lost to follow-up or who discontinued treatment due to compliance) and was 85.8% (127/148) in patients with data available in an intention-to-treat analysis. Nineteen patients were lost to follow-up; nine genotype 3 patients, nine nongenotype 3 patients and one mixed genotype patient. One patient relapsed, and one died, unrelated to treatment. Adverse events (>5%) were fatigue and headache. Two serious adverse events occurred; no adverse events resulted in drug discontinuation. An 8-week glecaprevir/pibrentasvir therapy was effective and well-tolerated in this real-world analysis.

Glecaprevir/pibrentasvir is safe and effective in hepatitis C patients with cirrhosis: Real-world data from the German Hepatitis C-Registry.

Glecaprevir/pibrentasvir is a pangenotypic direct-acting antiviral regimen approved for treating chronic hepatitis C virus. Real-world use of protease-inhibitor-containing regimens requires further evaluation in patients with cirrhosis. We evaluated the real-world safety and effectiveness of glecaprevir/pibrentasvir in patients with cirrhosis from the German Hepatitis C-Registry who initiated treatment between 2 August 2017 and 30 June 2019. Overall, 131 patients received 12-week (on-label) treatment and 51 received 8-week (off-label) treatment. No patient discontinued treatment due to adverse events. Four patients had serious adverse events; none were considered related to glecaprevir/pibrentasvir. Two patients had total bilirubin > 5 × upper limit of normal (ULN) during treatment. Three patients had alanine aminotransferase and three patients had aspartate aminotransferase > 3 × ULN. Rates of sustained virologic response were 100% (86/86) for 86 patients with available data. Glecaprevir/pibrentasvir treatment was well-tolerated and highly effective in patients with chronic hepatitis C and cirrhosis in real-world practice.

Correction to: Real-World Clinical Practice Use of 8-Week Glecaprevir/Pibrentasvir in Treatment-Naïve Patients with Compensated Cirrhosis.

In the original article, there is an error in Fig. 1.

Real-World Clinical Practice Use of 8-Week Glecaprevir/Pibrentasvir in Treatment-Naïve Patients with Compensated Cirrhosis.

INTRODUCTION: More than 70 million people are estimated to be infected with hepatitis C virus globally. Glecaprevir/pibrentasvir is a widely used treatment and has recently been approved for an 8-week regimen for treatment-naïve patients with compensated cirrhosis in Europe and the USA, who would previously have received glecaprevir/pibrentasvir for 12 weeks. This label update was based on the EXPEDITION-8 study, which included 343 treatment-naïve patients with compensated cirrhosis. However, there is currently a lack of similarly large-scale real-world studies of the 8-week glecaprevir/pibrentasvir regimen in this population. METHODS: This summary of seven separate smaller real-world studies aims to validate the results seen in EXPEDITION-8 and provide an up-to-date real-world reference for clinicians making treatment decisions for patients with compensated cirrhosis (Child-Pugh A) who may benefit from a shorter-duration therapy with glecaprevir/pibrentasvir. The newly emerging real-world effectiveness data on treatment-naïve patients with compensated cirrhosis treated with 8 weeks of glecaprevir/pibrentasvir help to understand where further research is needed to support patients with hepatitis C virus. RESULTS: Across all seven studies, glecaprevir/pibrentasvir showed high effectiveness with an average sustained virologic response rate of 98.1%, similar to that found in a clinical trial setting (99.7%). Only one patient (0.5%) experienced virologic failure and treatment was well tolerated. CONCLUSION: Expanding the number of patients eligible for the shortened treatment duration will potentially increase treatment initiation and completion, particularly in underserved populations, contributing to the elimination of hepatitis C virus.

Real-world effectiveness and safety of glecaprevir/pibrentasvir for the treatment of chronic hepatitis C infection: data from the German Hepatitis C-Registry.

BACKGROUND: Glecaprevir/pibrentasvir is a pangenotypic direct-acting antiviral regimen approved for treating adults chronically infected with hepatitis C virus (HCV). There are limited real-world data on glecaprevir/pibrentasvir to date. AIM: To evaluate the effectiveness and safety of glecaprevir/pibrentasvir under real-world conditions in the German Hepatitis C-Registry (DHC-R). METHODS: The DHC-R is an ongoing, non-interventional, multicentre, prospective, observational cohort study that monitors patients with chronic HCV infection. Data were collected from patients who initiated glecaprevir/pibrentasvir and completed a screening visit on or after 2 August 2017. The primary effectiveness endpoint was sustained virological response at post-treatment Week 12 (SVR12). Safety and tolerability were also assessed. RESULTS: As of 15 July 2018, 586 patients received glecaprevir/pibrentasvir and had documented SVR12 data, treatment discontinuation, loss to follow-up or HCV reinfection. Five hundred and fifty-two patients (94%) received on-label treatment. At baseline, most on-label patients were infected with HCV genotype 1 (53%) or 3 (33%), HCV treatment-naïve (90%), without cirrhosis (94%), and treated for 8 weeks (93%). Five hundred and thirty-four patients (96.7%) achieved SVR12 (intention-to-treat [ITT] analysis). By modified ITT analysis (excluding patients who discontinued and did not achieve SVR12 or patients lost to follow-up), the SVR12 rate was 99.4% (n/N = 534/537). There was one documented virological failure (relapse) and two documented HCV reinfections. One hundred and forty-two (26%) adverse events (AEs) and 9 (2%) serious AEs occurred; 2 (<1%) AEs led to treatment discontinuation. All patients treated off-label (N = 34) achieved SVR12. CONCLUSION: Glecaprevir/pibrentasvir was highly effective and well tolerated under real-world conditions. Clinical trial number: DRKS00009717 (German Clinical Trials Register, DRKS).

Development and evaluation of an algorithm to facilitate drug prescription for inpatients with feeding tubes.

PURPOSE: We aimed to develop and evaluate an algorithm to facilitate drug switching between primary and tertiary care for patients with feeding tubes. METHODS: An expert consortium developed an algorithm and applied it manually to 267 preadmission drugs of 46 patients admitted to a surgical ward of a tertiary care university hospital between June 12 and December 2, 2013, and requiring a feeding tube during their inpatient stay. RESULTS: The new algorithm considered the following principles: Drugs should be ideally listed on the hospital drug formulary (HDF). Additionally, drugs should include the same ingredient instead of a therapeutic equivalent. Preferred dosage forms were appropriate liquids, followed by solid drugs with liquid administration form, and solid drugs that could be crushed and/or suspended. Of all evaluated drugs, 83.5% could be switched to suitable drugs listed on the HDF and another 6.0% to drugs available on the German drug market. Additionally, for 4.1% of the drugs, the integration of individual switching rules allowed the switch from enteric-coated to immediate-release drugs. Consequently, 6.4% of the drugs could not be automatically switched and required case-to-case decision by a clinical professional (e.g., from sustained-release to immediate-release). CONCLUSIONS: The predefined principles were successfully integrated in the new algorithm. Thus, the algorithm switched more than 90% of the evaluated preadmission drugs to suitable drugs for inpatients with feeding tubes. This finding suggests that the algorithm can readily be transferred to an electronic format and integrated into a clinical decision support system.

Inappropriate crushing information on ward lists: cytotoxic drugs, capsules, and modified release formulations are gravely neglected.

PURPOSE: The aim of this study was to assess the quality of the information sources on the modification of solid medication dosage forms (crushing, suspending) used on the wards of a large university hospital in Germany. METHODS: We performed on-site visits of all 79 wards of the hospital and collected available sources of information on the modification of solid medication dosage forms. To evaluate the quality of such information, we gathered reference information for each listed brand from the respective pharmaceutical company, transferred this information to a knowledge base, and classified it into three categories, i.e., modification not allowed, modification allowed, and modification allowed under certain circumstances. RESULTS: Twenty-two lists of information on drug modification were identified in the 79 wards. Each list contained errors, and on average 17.0 % (range 8.0-32.3 %) of the brands listed had been withdrawn from the market or the information on crushing and/or suspending was inappropriate. Most of the incorrect information either concerned brands containing ingredients that were potentially hazardous to the staff members who prepared the drugs or referred to special dosage forms such as capsules and modified release formulations (e.g., cytotoxic drugs). CONCLUSION: We found that the lists posted on the wards were often outdated and did not take into account the limitations/problems of preparing drugs on the ward. Our results emphasize that lists posted in wards need to be checked regularly and that "ready-to-use" lists from third parties might require adaptation to site-specific conditions in order to protect healthcare staff from exposure to potentially hazardous drugs during drug preparation and ensure safe drug application to the patient.

Safeguarding the process of drug administration with an emphasis on electronic support tools.

AIMS: The aim of this work is to understand the process of drug administration and identify points in the workflow that resulted in interventions by clinical information systems in order to improve patient safety. METHODS: To identify a generic way to structure the drug administration process we performed peer-group discussions and supplemented these discussions with a literature search for studies reporting errors in drug administration and strategies for their prevention. RESULTS: We concluded that the drug administration process might consist of up to 11 sub-steps, which can be grouped into the four sub-processes of preparation, personalization, application and follow-up. Errors in drug handling and administration are diverse and frequent and in many cases not caused by the patient him/herself, but by family members or nurses. Accordingly, different prevention strategies have been set in place with relatively few approaches involving e-health technology. CONCLUSIONS: A generic structuring of the administration process and particular error-prone sub-steps may facilitate the allocation of prevention strategies and help to identify research gaps.

Development of a standardized knowledge base to generate individualized medication plans automatically with drug administration recommendations.

AIMS: We aimed to develop a generic knowledge base with drug administration recommendations which allows the generation of a dynamic and comprehensive medication plan and to evaluate its comprehensibility and potential benefit in a qualitative pilot study with patients and physicians. METHODS: Based on a literature search and previously published medication plans, a prototype was developed and iteratively refined through qualitative evaluation (interviews with patients and focus group discussions with physicians). To develop the recommendations for safe administration of specific drugs we screened the summary of product characteristics (SmPC) of different exemplary brands, allocated the generated advice to groups with brands potentially requiring the same advice, and reviewed these allocations regarding applicability and appropriateness of the recommendations. RESULTS: For the recommendations, 411 SmPCs of 140 different active ingredients including all available galenic formulations, routes of administrations except infusions, and administration devices were screened. Finally, 515 distinct administration recommendations were included in the database. In 926 different generic groups, 29,879 allocations of brands to general advice, food advice, indications, step-by-step instructions, or combinations thereof were made. Thereby, 27,216 of the preselected allocations (91.1%) were confirmed as appropriate. In total, one third of the German drug market was labelled with information. CONCLUSIONS: Generic grouping of brands according to their active ingredient and other drug characteristics and allocation of standardized administration recommendations is feasible for a large drug market and can be integrated in a medication plan.

Opportunities to reduce medication regimen complexity: a retrospective analysis of patients discharged from a university hospital in Germany.

BACKGROUND: Numerous characteristics of a medication regimen can weaken patient adherence to drug therapy and thus impair clinical outcomes of drug therapy. OBJECTIVE: The aim of the study was to investigate the prevalence of medication regimen characteristics that are known to reduce patient adherence to drug therapy. Furthermore, we assessed to what extent complex medication regimens can possibly be simplified through different strategies. METHODS: We retrospectively evaluated the medication regimens of 500 consecutive patients discharged from the University Hospital of Heidelberg, Germany, in whom the dosages of all drugs were specified. The medication regimens were extracted from the discharge letters issued between 1 January 2007 and 29 December 2007. Each medication regimen was checked for the presence of seven regimen characteristics that are known to reduce patient adherence, and theoretical viable strategies to avoid four of the respective characteristics were identified. The extent of possible simplification through the identified strategies was evaluated for the overall study population and the subgroup of elderly patients (≥65 years) with polypharmacy (≥5 drugs). RESULTS: On average, every medication regimen in the overall study population had 2.9±1.7 (standard deviation) characteristics (range 0-7) known to impair patient adherence. In contrast, the medication regimens of elderly patients with polypharmacy contained 3.7±1.6 characteristics (range 0-7) known to impair patient adherence. The most prevalent complexity characteristics in the overall study population were prescription of ≥1 drug with multiple doses per day (441 patients), ≥3 drugs with different dosing intervals (349 patients), tablet splitting (223 patients), followed by ≥12 daily drug administrations (190 patients). Almost half of the prescribed tablet splitting could be prevented. Moreover, 17.9% of the multi-dose prescriptions could be switched to once-daily dosing, and thus reduced the number of drugs with different dosing intervals and the number of daily drug administrations. The combined intervention reduced the total number of potentially preventable complexity characteristics by 18.3% (from 2283 to 1865 characteristics) without reducing prescription quality. CONCLUSION: Almost one-fifth of all regimen complexity characteristics relevant for patient adherence were avoidable by simple modifications of the medication scheme, stressing the need for targeted interventions.