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Stefano Fagiuoli,1 Pierluigi Toniutto,2 Nicola Coppola,3 Domenica Daniela Ancona,4 Margherita Andretta,5 Fausto Bartolini,6 Fulvio Ferrante,7 Alessandro Lupi,8 Stefano Palcic,9 Francesca Vittoria Rizzi,10 Davide Re,11 Gema Alvarez Nieto,12 Candido Hernandez,13 Francesca Frigerio,14 Valentina Perrone,14 Luca Degli Esposti,14 Alessandra Mangia15 1Department of Medicine and Surgery, University of Milan Bicocca & Gastroenterology Hepatology and Transplantation Unit, ASST Papa Giovanni XXIII, Bergamo, Italy; 2Hepatology and Liver Transplantation Unit, Azienda Ospedaliero Universitaria, Udine, Italy; 3Infectious Diseases Unit, University of Campania L. Vanvitelli, Naples, Italy; 4Dipartimento Farmaceutico ASL BAT, Trani, Italy; 5UOC Assistenza Farmaceutica Territoriale, Azienda Ulss 8 Berica, Vicenza, Italy; 6Dipartimento Farmaceutico-Usl Umbria 2, Terni, Italy; 7Dipartimento Diagnostica Ed Assistenza Farmaceutica – ASL Frosinone, Frosinone, Italy; 8Struttura Complessa Di Cardiologia – ASL VCO, Omegna, Italy; 9Farmaceutica Territoriale- Azienda Sanitaria Universitaria Integrata Giuliano-Isontina (ASUGI), Trieste, Italy; 10UOS Farmacovigilanza e Monitoraggio Spesa Farmaceutica- ASL BAT, Trani, Italy; 11Servizio Farmaceutico Territoriale ASL Teramo, Teramo, Italy; 12Gilead Sciences, Medical Affairs Italy, Milan, Italy; 13Gilead Sciences, Global Medical Affairs, London, UK; 14Clicon S.r.l., Health Economics and Outcomes Research, Bologna, Italy; 15Gastroenterology and Transplant Hepatology, Papa Giovanni XXIII Hospital, Bergamo, 24127, ItalyCorrespondence: Luca Degli Esposti, CliCon S.r.l. Società Benefit, Health, Economics & Outcomes Research, Via Murri, 9, Bologna, 40137, Italy, Tel +390544 38393, Email luca.degliesposti@clicon.itPurpose: The study aims at investigating the impact of polymedication and aging in the prevalence of multiple drug-drug interactions (DDIs) on HCV patients treated with sofosbuvir/velpatasvir (SOF/VEL) or glecaprevir/pibrentasvir (GLE/PIB).Patients and Methods: This is a retrospective analysis based on administrative data covering around 6.9 million individuals. Patients treated with SOF/VEL or GLE/PIB over November 2017–March 2020 were included. Index date corresponded to SOF/VEL or GLE/PIB first prescription during such period; patients were followed up for treatment duration. Analyses were then focused on patients with ≥ 2 comedications at risk of multiple DDIs. The severity and the effect of multiple DDI were identified using the Liverpool University tool.Results: A total of 2057 patients with SOF/VEL and 2128 with GLE/PIB were selected. Mean age of SOF/VEL patients was 58.5 years, higher than GLE/PIB ones (52.5 years) (p < 0.001), and patients > 50 years were more present in SOF/VEL vs GLE/PIB cohorts: 72% vs 58%, (p < 0.001). Most prescribed co-medications were cardiovascular, alimentary and nervous system drugs. Proportion of patients with ≥ 2 comedications was higher in SOF/VEL compared to GLE/PIB cohort (56.5% vs 32.3%, p < 0.001). Those at high-risk of multiple DDIs accounted for 11.6% (N = 135) of SOF/VEL and 19.6% (N = 135) of GLE/PIB (p < 0.001) patients with ≥ 2 comedications. Among them, the potential effect of DDI was a decrease of DAA serum levels (11% of SOF/VEL and GLE/PIB patients) and an increased concentration of comedication serum levels (14% of SOF/VEL and 42% of GLE/PIB patients).Conclusion: This real-world analysis provided a thorough characterization on the burden of polymedication regimens in HCV patients treated with SOF/VEL or GLE/PIB that expose such patients to an increased risk of DDIs. In our sample population, SOF/VEL regimen was more frequently detected on elderly patients and on those with ≥ 2 comedications at risk of multi-DDI, ie, among patients characterized by higher rates of comorbidities and polypharmacy.Keywords: administrative database, glecaprevir/pibrentasvir, hepatitis C, sofosbuvir/velpatasvir, polymedication

Valentina Perrone,1 Elisa Giacomini,1 Diego Sangiorgi,1 Margherita Andretta,2 Fausto Bartolini,3 Alessandro Lupi,4 Fulvio Ferrante,5 Stefano Palcic,6 Davide Re,7 Luca Degli Esposti1 1CliCon S.r.l. Società Benefit – Health, Economics & Outcome Research, Bologna, Italy; 2UOC Assistenza Farmaceutica Territoriale, Azienda ULSS 8 Berica, Vicenza, Italy; 3Dipartimento Farmaceutico-USL Umbria 2, Terni, Italy; 4ASL VCO, Omegna (VB), Italy; 5ASL Frosinone, Frosinone, Italy; 6Azienda Sanitaria Universitaria Integrata Giuliano-Isontina (ASUGI), Trieste, Italy; 7U.O.C. Servizio Assistenza Farmaceutica Territoriale, ASL Teramo, Teramo, ItalyCorrespondence: Valentina Perrone, CliCon S.r.l. Società Benefit – Health, Economics & Outcome Research, Via Murri 9, Bologna, 40137, Italy, Tel +39 3450316494, Email valentina.perrone@clicon.itPurpose: The study aimed to analyze, in hypercholesterolemic patients under statin medication, patient characteristics and their lipid profile at baseline, the therapeutic pathway, and the pharmaco-utilization, using real-world data in Italy.Patients and Methods: A retrospective study was conducted using administrative databases of a sample of entities covering 6.5 million health-assisted individuals. Between January 2010 and June 2019, patients with non-familial hypercholesterolemia (nFH) were identified by 1) ≥ 1 low-density lipoprotein cholesterol (LDL-C) measurement (LDL-C assessment date was the index-date) and 2) statin prescription during 6 months before the index-date (pharmaco-utilization period). FH patients were defined by LDL-C evaluation, statin treatment during the pharmaco-utilization period, and a score ≥ 6 according to the Dutch Lipid Clinic Network criteria. nFH patients were divided into four exclusive cohorts based on CV-risk class: 1) with previous CV disease (CVD); 2) with diabetes mellitus; 3) with mixed-dyslipidemia diagnosis; 4) in primary-prevention. Based on LDL-C index values, patient was defined with LDL-C “controlled” if its levels were ≤ 70mg/dl (CVD), ≤ 100mg/dl (diabetes, FH), ≤ 130mg/dl (mixed-dyslipidemia, primary-prevention).Results: Overall 164,161 nFH patients were included (mean age 72 years, 51% male); of these, 46,782 (28.5%) were CVD (mean age 74 years, 66% male), 34,803 (21.2%) were diabetic (mean age 72 years, 51% male), 1617 (1%) were with mixed-dyslipidemia (mean age 71 years, 48% male) and 80,959 (49.3%) were in primary-prevention (mean age 71 years, 42% male). The proportion of nFH patients with controlled LDL-C was 41.2% for CVD, 73.6% for diabetic, 80.7% for mixed-dyslipidemia, and 79.5% for primary-prevention patients; 49% of nFH patients were adherent to therapy. Overall, 1287 FH patients (mean age 64 years, 42% male) were included; in 39.2% of the patients, LDL-C was controlled, and 44% of the patients were adherent to therapy.Conclusion: The results of this study highlighted non-optimal therapeutic management of hypercholesterolemic patients in Italian clinical practice, with a notable quote of patients non-adherent to therapy.Keywords: lipid-lowering agents, pharmacoutilization, real-world evidence, clinical practice

Luca Degli Esposti,1 Chiara Veronesi,1 Domenica Daniela Ancona,2 Margherita Andretta,3 Fausto Bartolini,4 Alberto Drei,5 Alessandro Lupi,6 Stefano Palcic,7 Davide Re,8 Francesca Vittoria Rizzi,2 Elisa Giacomini,1 Valentina Perrone1 1CliCon S.r.l. Health, Economics & Outcomes Research, Bologna, Italy; 2Dipartimento Farmaceutico, ASL BAT, Trani, Italy; 3UOC Assistenza Farmaceutica Territoriale, Azienda ULSS 8 Berica, Vicenza, Italy; 4Dipartimento Farmaceutico, Umbria 2, Terni, 05100, Italy; 5Deloitte, Milano, Italy; 6Cardiology Unit, ASL VCO, Omegna, Italy; 7Farmaceutica Territoriale, Azienda Sanitaria Universitaria Integrata Giuliano-Isontina, Trieste, Italy; 8UOC Assistenza Farmaceutica Territoriale, ASL Teramo, Teramo, ItalyCorrespondence: Valentina Perrone, Clicon Srl, Health, Economics and Outcomes Research, Via Murri 9, Bologna, 40137, Italy, Tel +39 544 38393, Fax +39 544 212699, Email valentina.perrone@Clicon.itPurpose: This real-world study investigates the direct healthcare costs from the perspective of the Italian Healthcare National Service of experienced statin users according to their level of adherence to therapy and to their cardiovascular (CV) profile in Italian settings of outpatients clinical practice.Patients and Methods: A retrospective observational analysis was performed based on administrative databases covering approximately 6 million health-assisted individuals. Adult patients with statins prescription between January 2014 and December 2016 were screened, and first prescription within this period was the index date. Follow-up lasted 1 year after index date. Only patients receiving statins prior index date (experienced statin users) were included and distributed in clusters based on their CV profile. Adherence was calculated during follow-up as proportion of days covered (PDC) and classified in low adherence (PDC< 40%), partial adherence (PDC=40– 79%) and adherence (PDC≥ 80%). Mean direct healthcare costs of drugs, hospitalizations, and outpatient services were evaluated during follow-up.Results: A total of 436,623 experienced statin users were included and distributed as follows: 5.5% in the previous CV events, 22.6% in diabetes, 55.7% in CV treatments and 16.2% in the no comorbidity cluster. Total mean annual cost/patient decreased from low adherent to adherent patients from € 4826 to € 3497 in previous CV events, from € 2815 to € 2360 in diabetes cluster, from € 2077 to € 1863 for patients with CV treatments. Same trend was reported for the cost item related to hospitalizations, which was the major determinant of the total costs. In previous CV event cluster, adherence was associated to a saving of € 879 on total costs.Conclusion: The study highlighted a decrease in overall mean costs as adherence levels increase, particularly for patients with previous CV events, showing how improving adherence could be associated to cost savings and suggesting suited strategy based on CV profile should be undertaken for adherence optimization.Keywords: direct costs, lipid-lowering drugs, medication adherence, real-life

Introduction: We aimed to compare the effectiveness and cost-effectiveness profiles of glucagon-like peptide-1 receptor agonist (GLP-1-RA), sodium-glucose cotransporter 2 inhibitor (SGLT2i), and dipeptidyl peptidase-4 inhibitor (DPP-4i) compared with sulfonylureas and glinides (SU)., Research Design and Methods: Population-based retrospective cohort study based on linked regional healthcare utilization databases. The cohort included all residents in Lombardy aged ≥40 years, treated with metformin in 2014, who started a second-line treatment between 2015 and 2018 with SU, GLP-1-RA, SGLT2i, or DPP-4i. For each cohort member who started SU, one patient who began other second-line treatments was randomly selected and matched for sex, age, Multisource Comorbidity Score, and previous duration of metformin treatment. Cohort members were followed up until December 31, 2022. The association between second-line treatment and clinical outcomes was assessed using Cox proportional hazards models. The incremental cost-effectiveness ratios (ICERs) were calculated and compared between newer diabetes drugs and SU., Results: Overall, 22 867 patients with diabetes were included in the cohort, among which 10 577, 8125, 2893 and 1272 started a second-line treatment with SU, DPP-4i, SGLT2i and GLP-1-RA, respectively. Among these, 1208 patients for each group were included in the matched cohort. As compared with SU, those treated with DPP-4i, SGLT2i and GLP-1-RA were associated to a risk reduction for hospitalization for major adverse cardiovascular events (MACE) of 22% (95% CI 3% to 37%), 29% (95% CI 12% to 44%) and 41% (95% CI 26% to 53%), respectively. The ICER values indicated an average gain of €96.2 and €75.7 each month free from MACE for patients on DPP-4i and SGLT2i, respectively., Conclusions: Newer diabetes drugs are more effective and cost-effective second-line options for the treatment of type 2 diabetes than SUs., Competing Interests: Competing interests: GC received research support from the European Community (EC), the Italian Agency of Drugs (AIFA), and the Italian Ministry of University and Research (MIUR). He took part in a variety of projects that were funded by pharmaceutical companies (ie, Novartis, GSK, Roche, AMGEN and BMS). He also received honoraria as a member of the advisory board to Roche., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

This real-world analysis evaluated the clinical and economic burden of non-dialysis-dependent CKD patients with and without secondary hyperparathyroidism (sHPT) in Italy. An observational retrospective study was conducted using administrative databases containing a pool of healthcare entities covering 2.45 million health-assisted individuals. Adult patients with hospitalization discharge diagnoses for CKD stages 3, 4, and 5 were included from 1 January 2012 to 31 March 2015 and stratified using the presence/absence of sHPT. Of the 5710 patients, 3119 were CKD-only (62%) and 1915 were CKD + sHPT (38%). The groups were balanced using Propensity Score Matching (PSM). Kaplan-Meier curves revealed that progression to dialysis and cumulative mortality had a higher incidence in the CKD + sHPT versus CKD-only group in CKD stage 3 patients and the overall population. The total direct healthcare costs/patient at one-year follow-up were significantly higher in CKD + sHPT versus CKD-only patients (EUR 8593 vs. EUR 5671, p < 0.001), mostly burdened by expenses for drugs (EUR 2250 vs. EUR 1537, p < 0.001), hospitalizations (EUR 4628 vs. EUR 3479, p < 0.001), and outpatient services (EUR 1715 vs. EUR 654, p < 0.001). These findings suggest that sHPT, even at an early CKD stage, results in faster progression to dialysis, increased mortality, and higher healthcare expenditures, thus indicating that timely intervention can ameliorate the management of CKD patients affected by sHPT.

Competing Interests: Conflict of interest: The Authors declare no potential conflict of interest with respect to the research, authorship and/or publication of this article. The authors declare the following competing interests: AMM, FC, GCo, AG, ML, MMed , MMel, SP, MP, FP, MZ declare no conflict of interest. WM reports holding a fiduciary role in FIMMG, EPCCS and Consulta. EA is an employee of Amgen and reports stock ownership in the company. MB is an employee of Sanofi. GB is an employee of Dephaforum. RC reported receiving consulting fees from MSD Italia, Eli Lilly Italy, Menarini Diagnostics, Roche Diabetes Care Italy, honoraria from Novo Nordisk, Sanofi, Abbott, Mundipharma Farmaceuticals, participation to an advisory boards supported by Boehringer Ingelheim. GCa reported receiving consulting fees from Novartis, Alexion, AstraZeneca, Abbvie, Astellas, Roche, Takeda, Jannsen and Biomarin. ACa reported receiving consulting fees from MSD Italia, Eli Lilly Italy, Menarini Diagnostics, Roche Diabetes Care Italy, honoraria from Novo Nordisk, Sanofi, Abbott, Mundipharma Farmaceuticals, participation to advisory boards supported by Boehringer Ingelheim. ACo reported receiving research grants by AstraZeneca, honoraria from Novo Nordisk, Eli Lilly, Merck Sharp & Dhome, participation on advisory boards supported by Novo Nordisk and Eli Lilly. GD reports stock ownership in Bristol Meyers Squibb. MDG is an employee of Sanofi and reports stock ownership in the company. EP is an employee or Gilead Sciences and reports stock ownership in the company. DS is an employee of Abbvie. VT reported receiving consulting fees from Biogen Italia and grants from FEEM Fondazione Eni Enrico Mattei. EC is an employee of Chiesi Italia.

Anaemia is a uraemia-related complication frequently found in non-dialysis-dependent chronic kidney disease (ND-CKD) patients, with iron-deficiency anaemia (IDA) as the main underlying mechanism. Given the suboptimal anaemia management in ND-CKD patients with a co-diagnosis of IDA, this study evaluated the role of IDA therapy on clinical outcomes and healthcare resource consumptions in an Italian clinical setting. A retrospective observational real-world analysis was performed on administrative databases of healthcare entities, covering around 6.9 million health-assisted individuals. From January 2010 to March 2019, ND-CKD patients were included and diagnosed with IDA in the presence of two low-haemoglobin (Hb) measurements. Patients were divided into IDA-treated and untreated, based on the prescription of iron [Anatomical-Therapeutic Chemical (ATC) code B03A] or anti-anaemia preparations (ATC code B03X), and evaluated during a 6-month follow-up from the index date [first low haemoglobin (Hb) detection]. IDA treatment resulted in significantly decreased incidence of all cause-related, cardiovascular-related, and IDA-related hospitalizations (treated vs. untreated: 44.5% vs. 81.8%, 12.3% vs. 25.3%, and 16.2% vs. 26.2%, respectively, p < 0.001). A healthcare direct cost estimation showed that overall mean expenditure per patient reduced by 47% with IDA treatment (5245€ vs. 9918€, p < 0.001), mainly attributable to hospitalizations (3767€ vs. 8486€, p < 0.001). This real-life analysis on Italian ND-CKD-IDA patients indicates that IDA therapy administration provides significant benefits in terms of patients’ clinical outcomes and healthcare cost savings.

This Italian real-world data analysis evaluated the pharmaco-utilization of calcimimetics, cinacalcet or etelcalcetide, and the economic burden of secondary hyperparathyroidism (SHPT) in chronic kidney disease (CKD) patients. From 1 January 2010 to 30 June 2020, adult patients with: (i) ≥1 prescription of etelcalcetide or cinacalcet, (ii) ≥3 hemodialysis/week, and (iii) without parathyroidectomy, were included. Based on the drug firstly prescribed, patients were allocated into etelcalcetide- and cinacalcet-treated cohorts, and the propensity score matching (PSM) methodology was applied to abate potential cohorts’ unbalances. Overall, 1752 cinacalcet- and 527 etelcalcetide-treated patients were enrolled. In cinacalcet- and etelcalcetide-treated patients, respectively, the most frequent comorbidities were hypertension (75.3% and 74.4%), diabetes mellitus (21.0% and 21.3%), and cardiovascular disease (18.1% and 13.3%, p < 0.01). In covariate-balanced cohorts, the treatment adherence and persistence rates were significantly higher in the etelcalcetide-treated (80.1% and 62.7%, respectively) vs. cinacalcet-treated cohort (62.3% and 54.7%, respectively). After PSM, the total costs for the management of cinacalcet- and etelcalcetide-treated patients, respectively, averaged EUR 23,480 and EUR 22,958, with the disease-specific drug costs (EUR 2629 vs. EUR 2355, p < 0.05) and disease-specific hospitalization costs (EUR 1241 vs. EUR 855) in cinacalcet- and etelcalcetide-treated patients. These results showed that, in etelcalcetide-treated patients, a higher treatment adherence and persistence was found, with disease-specific costs savings, especially those related to drugs and hospitalizations.

Biofilms pose a serious problem for public health. Penetration of pharmacological agents within a biofilm is hampered by the morphological structure of such microbial communities. A biofilm infection therefore entails adverse outcomes both in the field of cost management and patient prognosis. The problem is further complicated if the drugs available to combat a biofilm-related fungal infection versus a bacterial one are compared: in the case of a fungal infection, the drugs available are less efficacious than antibiotics used to counteract a bacterial infection. Furthermore, even the fairly recent introduction of antifungals, such as echinocandins, start presenting some limits of usage, such as ineffectiveness in treating some fungal populations and increased resistance. It therefore becomes imperative to search for innovative molecules in order to combat this condition. The discovery of new molecules and/or new targets can make a difference. This paper illustrates the main innovative molecules that are coming to light in the field of infection by fungal biofilms.