Comparative Effectiveness of Biosimilar, Reference Product and Other Erythropoiesis-Stimulating Agents (ESAs) Still Covered by Patent in Chronic Kidney Disease and Cancer Patients: An Italian Population-Based Study

Background Since 2007 biosimilars of erythropoiesis-stimulating agents (ESAs) are available on the Italian market. Very limited post-marketing data exist on the comparative effectiveness of biosimilar and originator ESAs. Aim This population-based study was aimed to compare the effects of biosimilars, reference product and other ESAs still covered by patent on hemoglobinemia in chronic kidney disease (CKD) and cancer patients in a Local Health Unit (LHU) from Northern Italy. Methods A retrospective cohort study was conducted during the years 2009-2014 using data from Treviso LHU administrative database. Incident ESA users (no ESA dispensing within 6 months prior to treatment start, i.e. index date (ID)) with at least one hemoglobin measurement within one month prior to ID (baseline Hb value) and another measurement between 2nd and 3rd month after ID (follow-up Hb value) were identified. The strength of the consumption (as total number of defined daily dose (DDD) dispensed during the follow-up divided by days of follow-up) and the difference between follow-up and baseline Hb values [delta Hb (ΔHb)] were evaluated. Based on Hb changes, ESA users were classified as non-responders (ΔHb≤0 g/dl), responders (0Delta;Hb≤2 g/dl), and highly responders (ΔHb>2 g/ dl). A multivariate ordinal logistic regression model to identify predictors for responsiveness to treatment was performed. All analyses were stratified by indication for use and type of dispensed ESA at ID. Results Overall, 1,003 incident ESA users (reference product: 252, 25.1%; other ESAs covered by patent: 303, 30.2%; biosimilars: 448, 44.7%) with CKD or cancer were eligible for the study. No statistically significant difference in the amount of dose dispensed during the follow-up among biosimilars, reference product and other ESAs covered by patent was found in both CKD and cancer. After three months from treatment start, all ESAs increased Hb values on average by 2g/dl. No differences in ΔHb as well as in frequency of non-responders, responders and highly responders among different types of ESAs were observed in both indications of use. Overall, around 15-20% of ESA users were non-responders. Strength of treatment, but no type of dispensed ESAs was found to be predictor of responsiveness to treatment. Conclusions No difference on the effects on hemoglobinemia among users of either biosimilars or reference product or ESAs covered by patent was observed in a general population from Northern Italy, despite a comparable dispensed dose of the different ESAs during the first three months of treatment

How Have Intravitreal Anti-VEGF and Dexamethasone Implant Been Used in Italy? A Multiregional, Population-Based Study in the Years 2010-2016

Purpose: To describe intravitreal anti-VEGF drug and dexamethasone use in four Italian regions.Methods: Four regional claims databases were used to measure drug prevalence, compare dosing intervals to those recommended in the summary of product characteristics (SPC), and identify switchers. Bilateral treatment and diabetic macular edema (DME) coding algorithms were validated, linking claims with a sample of prospectively collected ophthalmological data.Results: Overall, 41,836 patients received 651 study drug in 2010-2016 (4.8 per 10,000 persons). In 2016, anti-VEGF drug use ranged from 0.8 (Basilicata) to 5.7 (Lombardy) per 10,000 persons while intravitreal dexamethasone use ranged from 0.2 (Basilicata) to 1.4 (Lombardy) per 10,000 persons. Overall, 40,815 persons were incident users of study drugs. Among incident users with 651 year of follow-up (N = 30,745), 16.0% (N = 30,745), 16.0% (N = 30,745), 16.0% (.Conclusion: Study drug use increased over time in Lombardy, Basilicata, Calabria, and Sicily, despite a large heterogeneity in prevalence of use across regions. Drug treatment appeared to be partly in line with SPC, suggesting that improvement in clinical practice may be needed to maximize drug benefits

Challenges in Post-marketing Studies of Biological Drugs in the Era of Biosimilars: A Report of the International Society for Pharmacoepidemiology 2019 Mid-Year Meeting in Rome, Italy

Several controversial issues related to challenges in the post-marketing studies of biological drugs, including biosimilars, were discussed at the International Society for Pharmacoepidemiology (ISPE) 2019 Mid-Year Meeting in Rome (Italy) in April. In recent years, the marketing of biosimilars has been growing, thus offering opportunities for wider access by patients to high-cost biological drugs as well as ensuring the economic sustainability of national healthcare systems. Through the comparability exercise required for marketing approval, the similarity of biosimilars to the reference products in terms of efficacy, safety and quality has to be demonstrated in pre-marketing studies. In Europe, the 15\ua0years of experience of marketing of biosimilars has allowed the accumulation of a significant amount of scientific evidence confirming the comparability of the benefit\u2013risk profile of biosimilars and originators. However, some aspects remain to be addressed both from a scientific and regulatory perspective, such as interchangeability and the automatic substitution of originators and biosimilars. The (long-term) monitoring of all biological drugs, including biosimilars, in real-world settings is warranted, with the ultimate goal of integrating pre- and post-marketing evidence relating to the aforementioned open questions. This conference report describes priorities, data sources and methodological strategies for the post-marketing surveillance of biological drugs in the era of biosimilars

Adverse drug reactions associated with off-label use of ketorolac, with particular focus on elderly patients. An analysis of the Italian pharmacovigilance database and a population based study

This study aims to evaluate the frequency of off-label use of ketorolac in Italy and the related suspected adverse drug reactions (ADRs) reported

Pharmacokinetics of new oral anticoagulants: implications for use in routine care

Introduction: Since 2008, new oral anticoagulants (NOACs) have been approved for the prevention of venous thromboembolism (VTE) in patients receiving hip or knee replacement surgery, prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation (NVAF), treatment of deep vein thrombosis (DVT), and pulmonary embolism (PE). Premarketing randomized clinical trials (RCTs) of NOACs demonstrated their non-inferiority in terms of efficacy vs. warfarin (traditional oral anticoagulant–TOA), with lower risk of serious adverse drug reactions, especially cerebral hemorrhages. In clinical practice, pharmacokinetic aspects of NOACs have to be carefully taken into account to optimize the benefit-risk profile of these drugs. Areas covered: An overview of major issues related to pharmacokinetics of NOACs, such as drug–drug interactions, over- and underdosage in special populations (e.g. elderly, underweight, and chronic kidney disease patients), and impact on adherence and persistence to NOACs therapy and ultimately clinical outcomes in real-world setting, is provided. Expert opinion: NOACs have been proven to be a better option than traditional anticoagulants due to better tolerability and ease of use. However, given specific pharmacokinetic characteristics, NOAC therapy has to be carefully tailored and monitored in relation to patient characteristics with the final goal of maximizing benefits and minimizing risks

Expert Opin Drug Saf

INTRODUCTION: Adverse drug reactions (ADRs) are an important cause of morbidity and mortality worldwide. They are associated with healthcare costs due to hospital admissions or prolonged length of stay (LOS), as well as additional interventions. The aim of this study was to conduct a systematic review of observational studies to evaluate the economic impact of preventable ADRs. Areas covered: Published observational research investigating the cost of preventable ADRs in Western countries (limited to the US and European countries). Expert opinion: Several reviews have been carried out in the field of the ADR epidemiology but fewer reviews have investigated the economic impact of ADRs, and at the time of writing, none has focused on preventable ADRs. The reason why future research should focus on the costs of preventable ADRs is that both the costs and the clinical outcomes are preventable, and as such, are a key point of public health policy action. Nevertheless, the present review highlights an important and sobering limitation of published research on the cost of preventable ADRs, of which the major limitation is the heterogeneity in methods and in reporting limit what can be known through a summarizing work of a systematic review

Medication is an additional source of phosphate intake in chronic kidney disease patients

Background and aims: Hyperphosphatemia increases the risk of cardiovascular morbidity but the use of medicines as a source of phosphate has not been investigated yet. This study aims to explore the use of absorbable phosphate-containing drugs in CKD patients. Methods and results: Incident CKD patients were identified within the Arianna database (containing data from 158,510 persons in Caserta (Southern Italy) registered with 123 general practitioners) from 2005 to 2011. Drugs prescribed to these patients were classified as phosphate-containing based on the summary of product characteristics (SPC), PubChem and Micromedex. The number and duration of prescriptions for these drugs as well as the overall intake of phosphate were estimated.Out of 1989 CKD patients, 1381 (70%) were prescribed 266 medicinal products containing absorbable phosphate over a median follow-up of 6 years (interquartile range (IQR) = 5.2-6.0). Most patients were prescribed ATC A (650; 47.1%) and C (660; 47.8%) phosphate-containing drug products targeting the gastrointestinal and cardiovascular system for a median of 232 (IQR: 56-656) and 224 (IQR: 56-784) days respectively. Conclusions: Several medications, especially chronically prescribed ones, contain absorbable phosphate. This study's findings confirm the relevance of medicines as a phosphate source for the first time