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Purpose: Hepatitis C virus (HCV) spreads from contact with blood of an infected person. HCV infections are common among people who use drugs (PWUDs), when sharing needles, syringes, or other equipment for injected drugs. The advent of pangenotypic direct-antiviral agents (DAA) in 2017 transformed the treatment landscape for HCV, but PWUDs remain a complex and hard-to-treat population with high risk of HCV reinfection. The aim of this real-world analysis was to characterize the demographic and clinical features of PWUDs in Italy, also focusing on comorbidity profile, treatment with DAAs, resource consumptions for the National Health System (NHS)., Patients and Methods: During 01/2011-06/2020, administrative databases of Italian healthcare entities, covering 3,900,000 individuals, were browsed to identify PWUDs with or without HCV infection. Among HCV+ patients, a further stratification was made into treated and untreated with DAAs. The date of PWUD or HCV first diagnosis or DAA first prescription was considered as index-date. Patients were then followed-up for one year. Alcohol-dependency was also investigated., Results: Total 3690 PWUDs were included, of whom 1141 (30.9%) PWUD-HCV+ and 2549 (69.1%) PWUD-HCV-. HCV-positive were significantly older (43.6 vs 38.5 years, p < 0.001), had a worse comorbidity profile (Charlson-index: 0.8 vs 0.4, p < 0.001), and high rates of psychiatric, respiratory, dermatological, musculoskeletal diseases and genitourinary (sexually transmitted) infections. Moreover, they received more drug prescriptions (other than DAAs, like anti-acids, antiepileptics, psycholeptics) and had undergone more frequent hospitalization, predominantly for hepatobiliary, respiratory system and mental disorders. DDA-untreated had significantly higher Charlson-index than DAA-treated (0.9 vs 0.6, p = 0.003). Alcoholism was found in 436 (11.8%) cases., Conclusion: This Italian real-world analysis suggests that PWUDs with HCV infection, especially those untreated with DAAs, show an elevated drug consumption due to their complex clinical profile. These findings could help to ameliorate the healthcare interventions on PWUDs with HCV infection., Competing Interests: A.M. declares teaching and speaking and research support: Angelini, Gilead Sciences, Polifarma. F.F and C.H are employees of Gilead Sciences. M.P. reports grants, personal fees, non-financial support from Gilead, AbbVie; personal fees from Merck, during the conduct of the study; personal fees from Angelini, Astra Zeneca, GSK, Menarini, Janssen, Roche, and Novartis, outside the submitted work. All other authors report no conflicts of interest in this work., (© 2023 Nava et al.)

Purpose: An Italian real-world retrospective study was conducted in patients with psoriasis (PSO) to evaluate their characteristics, treatment patterns, and biological/targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD) drug utilization., Patients and Methods: The retrospective analysis was carried out on real-world data collected from administrative databases of selected Italian health-departments; the dataset covered approximately 22% of the Italian population. PSO patients (identified by PSO hospitalization, and/or active exemption code and/or a topical anti-psoriatic medication prescription) were included. In prevalent patients identified during 2017-2018-2019-2020, baseline characteristics and treatment patterns were investigated. Moreover, b/tsDMARD drug utilization (focusing on persistence, monthly dosage, and mean duration between prescriptions) was evaluated in bionaïve patients included during 2015 and 2018., Results: PSO was diagnosed in 241,552 (in 2017), 269,856 (in 2018), 293,905 (in 2019) and 301,639 (in 2020) patients. At the index date, almost 50% of patients had not received systemic medications, and 2% had received biological treatment. Among the b/tsDMARD-treated patients, a decrease in the use of tumour necrosis factor (TNF) inhibitors (60.0-36.4%, from 2017 to 2020) and an increase in the use of interleukin (IL) inhibitors (36.3-50.6%, from 2017 to 2020) were observed. In 2018, the persistence rates of TNF inhibitors and IL inhibitors in bionaïve patients ranged from 60.8-79.7% and 83.3-87.9%, respectively., Conclusion: This real-world study of PSO drug utilization in Italy showed that a significant number of patients were not treated with systemic medications and only 2% of patients were treated with biologics. An increase in the use of IL inhibitors and a decrease in the prescription of TNF inhibitors over years were found. Patients treated with biologics were highly persistent with treatment. These data provide insight into routine clinical practice for PSO patients in Italy, suggesting that the optimization of treatment for PSO still represents an unmet medical need., Competing Interests: VP, MD, DS, and LDE are affiliated with CliCon S.r.l. Società Benfit. SL, SS and MM are employees of Eli Lilly S.p.A Italy. SL is a stockholder of Eli Lilly S.p.A Italy. The authors report no other conflicts of interest in this work., (© 2023 Perrone et al.)

Purpose: 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., Competing Interests: SF reports speaking/consulting/research for AbbVie, Astellas, Bayer, Gilead, Intercept, Roche, Eisai, Kedrion, MSD, Novartis. PT reports speaking/consulting/research for AbbVie, Bayer, Gilead. NC reports speaking/consulting/research for AbbVie, Bristol, Gilead, Janssen, Merck, ViiV Healthcare, MSD. CH, GAN, FF are employees of Gilead. LDE, VP are employees of Clicon S.r.l. Società Benefit, Health Economics and Outcomes Research. AM reports speaking/consulting/research for Angelini, Gilead, Intercept, MSD, Spring Bank. All the remaining authors reports no conflicts of interest in this work., (© 2023 Fagiuoli et al.)

Purpose: A retrospective analysis of real-world data was performed to assess the epidemiology and economic burden of multiple sclerosis (MS), relapsing-remitting MS (RRMS), and secondary-progressive MS (SPMS) in Italy., Patients and Methods: An observational study on administrative databases from a sample of Italian entities was carried-out. Between 01/2010-12/2017, patients with ≥1 MS diagnosis code (ICD-9-CM:340 and/or exemption code:046) and/or ≥1 disease-modifying therapies (DMTs) prescription, were included. Among MS-cohort, SPMS patients were identified by ≥2 hospitalizations or by ≥2 drug prescriptions related to MS progression. MS patients not fulfilling SPMS criteria were included as RRMS. Mean annual healthcare costs were reported during follow-up and stratified by DMT treatment/untreatment., Results: Overall, 9543 MS patients were included; 8397 with RRMS and 1146 with SPMS. Estimated prevalence of MS was 141.6/100,000 inhabitants (RRMS 124.4/100,000 and SPMS 17.2/100,000). Mean annual cost for untreated and treated patient was respectively: €3638 and €11796 (MS-cohort), €3183 and €11486 (RRMS-cohort), €6317 and €15511 (SPMS-cohort). The first-line DMT treatment duration averaged 27.4 ± 22.8 months; the mean cost was 19004€ for the whole period. The second-line DMT treatment lasted on average 31.1 ± 24.5 months; the mean cost was 47293€ for the whole period., Conclusion: This study provided insights into the MS epidemiology in Italy and its economic burden. Healthcare costs associated with MS management were mainly driven by DMTs expenditure. A trend of higher healthcare-resource consumption was observed among SPMS-cohort., Competing Interests: This study was sponsored by Novartis Pharma S.p.A, under an agreement between Novartis Pharma S.p.A and Clicon S.r.l. Società Benefit. Clicon S.r.l. Società Benefit is an independent company. The agreement sign by Clicon S.r.l. Società Benefit and Novartis Pharma AG does not create any entityship, joint venture or any similar relationship between parties. Neither CliCon S.r.l. Società Benefit nor any of their representatives are employees of Novartis Pharma for any purpose. MN and DR are employees of Novartis Pharma. All other authors report no other conflicts of interest in this work., (© 2022 Perrone et al.)

Purpose: 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., Competing Interests: Novartis Farma S.p.A. purchased the study report that is the basis for this manuscript. This manuscript was developed by CliCon S.r.l. Società Benefit and sponsored by Novartis Farma S.p.A. All authors report no conflicts of interest in this work. The agreement signed by Clicon S.r.l. Società Benefit and Novartis Farma S.p.A. does not create any entity hip, joint venture or any similar relationship between parties. Clicon S.r.l.Società Benefit is an independent company. Neither CliCon S.r.l. Società Benefit nor any of their representatives are employees of Novartis Farma S.p.A. for any purpose., (© 2022 Perrone et al.)

Purpose: A retrospective analysis was conducted to estimate the number of patients with focal epilepsy and drug-resistant epilepsy (DRE) and their characteristics, the therapeutic patterns, the consumption of health resources in a real-world Italian setting., Patients and Methods: A retrospective study was carried out on the administrative databases of a sample of Italian Health Departments, covering approximately 8.7 million health-assisted individuals. All adult patients with at least one hospitalization for focal epilepsy and an electroencephalogram (between 01/2010 and 12/2019), and at least one prescription of antiseizure medication (ASM) (between 01/2011 and 12/2018) were included in the study. Patients with at least two treatment failures and treated with a subsequent ASM were considered DRE., Results: Overall, 1897 patients with focal epilepsy (mean age 56 years, 47% male) were identified, of which 485 (25.6%) with DRE (mean age 53 years, 43% male). Among patients with focal epilepsy and DRE, respectively, 48% and 54% had essential hypertension, 23.4% and 26.6% had cardiovascular disease, and 46.3% and 62.1% had peptic ulcer/prescription of gastric secretion inhibitors. During follow-up, patients with focal epilepsy maintained first-line treatment for 53.9 months; among these, 52% passed to the second-line, and 485 (25.6% of the total) began third-line treatment. In patients with focal epilepsy, the mean cost was € 4448 (of which € 1410 were epilepsy-related), and in DRE patients total expenditures averages € 5825 (of which € 2165 were epilepsy-related). In both patients with focal epilepsy and DRE, hospitalizations represented the most impacting item of expenditure., Conclusion: The present analysis conducted in a setting of Italian clinical practice has shown that 25% of patients with focal epilepsy were resistant to antiepileptic treatments. Furthermore, these results showed that health-care costs for the management of epileptic patients were mainly accountable for the costs related to the disease-management and to hospitalizations., Competing Interests: V Perrone, C Veronesi, M Dovizio, DD Ancona, M Andretta, F Bartolini, A Cavaliere, A Chinellato, A Ciaccia, M Cillo, A De Francesco, N Enieri, F Ferrante, S Gentile, C Procacci, L Ubertazzo, A Vercellone, and L Degli Esposti report no conflicts of interest in this work. D Lucatelli and M Procaccini are employees of Angelini Pharma, Italy. The authors report no other conflicts of interest in this work., (© 2022 Perrone et al.)

Purpose: 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., Competing Interests: The authors report no conflicts of interest in this work., (© 2022 Degli Esposti et al.)

Purpose: To analyse the healthcare resource consumption and related costs for the Italian National Health System of patients estimated to be affected by treatment-resistant depression (TRD) in Italy., Patients and Methods: This was an observational retrospective study based on administrative databases, including those related to residential/semiresidential structures, of Veneto Region and the Local Health Unit of Bergamo in Italy (for a total of around 6 million health-assisted subjects). Between July 2011 and December 2017, all adult patients with a third antidepressant (AD) after ≥2 AD (each one with at least ≥4 weeks duration, ≥1 prescription at maximum dosage reported in datasheets, a grace period ≤30 days when switching AD and treatment maintained ≥9 months) were included. Overall and psychiatry-related healthcare resources consumption and related costs were estimated on a 12-months based analysis. Data were re-proportioned to the Italian population., Results: We have previously estimated a total of 101,455 patients with TRD in Italy (130,049 considering the mean maximum dosage of AD). Of them, 44.2% had at least a psychiatric hospitalization/visit or accessed a residential/semiresidential structure, and 31% added another AD or a mood stabilizer/antipsychotic drug. Patients with at least one psychiatry-related hospitalization increased over the number of antidepressant lines from 12.0% during first line up to 24.5% during fourth line. Direct healthcare costs increased from €4,405 for first line to €9,251 from fifth line onwards. Psychiatry-related costs went from €1,817 (first line) to €4,606 (fifth line onwards) and were mainly driven by residential/semiresidential structures and hospitalizations., Conclusion: An upward trend with number of AD lines was observed for all healthcare resource utilization and consequently for all direct costs, thus indicating an increasing burden for patients as they move forward AD lines., Competing Interests: VP, DS, and LDE are employees of Clicon S.r.l., an independent company. The agreement signed by Clicon S.r.l. and Janssen Italy does not create any entityship, joint venture or any similar relationship between parties. Neither CliCon S.r.l. nor any of their representatives are employees of Janssen Italy for any purpose. PCFM is an employee of Hemar Department, Janssen Italy. GM has been a consultant/speaker for: Angelini, Boehringer, Fb Health, Innovapharma, Italfarmaco, Janssen, Otsuka, Lundbeck, Sanofi. EZ has been a consultant for Johnson & Johnson, Otsuka, Lundbeck. All the remaining authors report no conflicts of interest., (© 2021 Perrone et al.)

Purpose: To date, litte evidence is reported about the real-life dosage of tyrosine kinase inhibitors prescribed in Italy. The present observational retrospective study aimed to evaluate the mean daily dose of nilotinib prescribed as first- and second-line therapy among patients suffering from chronic myeloid leukemia (CML) in settings of clinical practice in Italy., Patients and Methods: Data were obtained from the administrative databases of a sample of Italian entities. All adult patients prescribed nilotinib were included from January 2013 to December 2016 if they were using it as first-line and from January 2015 to December 2018 as second-line therapy. The mean daily dose was calculated considering the dosage between first and last nilotinib prescription date or last BCR/ABL test date., Results: Among CML patients treated with nilotinib as first-line (N=87), the mean daily dose of nilotinib was 500.5 mg during a mean treatment duration of 798.9 days and of 498.54 mg considering the last determination of BCR/ABL test (mean duration of 811 days). A total of 103 CML patients were prescribed nilotinib as second-line therapy; of them, 80.6% had previously received imatinib, 17.5% dasatinib. The mean daily dose of nilotinib was found to be 566.3 mg with a mean time duration of 302.8 days, while when the last BCR/ABL test was taken into account (mean duration of 323.1 days), a mean daily dose of 565.2 mg was detected., Conclusion: The study reported on the real-world dosage pattern of a TKI for CML management. Our results compared with the dosage of nilotinib reported in datasheet (600 mg and 800 mg for first- and second-line, respectively) showed a trend of mean daily dose prescribed in clinical practice settings lower than the dosage currently indicated., Competing Interests: The authors report no conflicts of interest in this work., (© 2021 Perrone et al.)

The 20th century witnessed the dawn of the antibiotic revolution and is now facing the rising phenomenon of antibiotic resistance. In this narrative review, we aim to describe antibiotic resistance in clinical practice settings through population-based studies from different countries reporting the role of misuse of antibiotics in the development of resistance and the clinical and economic burden associated. The misuse of antibiotics was documented in the wide population as well as in hospitals and care facilities. It was mainly reported as over-use and inappropriate prescribing. Improper dosage regimens and longer treatment duration were regarded as pivotal factors related to antibiotic resistance; the emerging strategy of "antibiotic-de-escalation" could be the key to overcome these issues. The investigation of the self-medication attitude revealed widespread antibiotic use without following medical instructions or medical consultation. Moreover, several studies established the association of antibiotic resistance with increased risk of longer hospitalizations and mortality, highlighting the heavy clinical and economic burden of this phenomenon. In this narrative review, the widespread inappropriate use of antibiotics emerged as one of the main causes of antibiotic resistance, which negative outcomes call for the development of antibiotic stewardship programs and global surveillance networks., Competing Interests: The authors report no conflicts of interest in this work., (© 2021 Giacomini et al.)

Poor medication adherence leads to worsening of clinical outcomes and increases healthcare costs, especially in the context of chronic conditions. The effects of new COVID-19 infection and the measures taken in response to the outbreak are further increasing the concerns about medication adherence. Patients with chronic diseases, many of whom are older adults, have been strongly recommended to stay at home and avoid social contacts even with family members, who often provide support for regular use of therapies. Moreover, the mobilization of health personnel to the frontline of the COVID-19 infection could limit access to healthcare services. Within the Health-DB project, the Fail-To-Refill monitoring system was designed to evaluate the lack of adherence to chronic therapies in Italian clinical practice settings. Considering the date and dose coverage of last prescription, all patients due to refill this prescription for a chronic therapy in the last month were identified, and it was verified if they had the refill. The proposed future analysis, based on the data linkage between the current administrative flows of the Italian Local Health Units involved, will be carried out on a monthly basis from the beginning of the infection, and the "post-Covid-19" results will be compared with "pre-COVID-19" results, calculated for the last three years for patients with chronic therapies. Preliminary data herein presented showed a trend of increased failed refill during the months of lockdown for lipid-lowering and biologic therapies. The pre-COVID-19 trend compared to that of post-COVID-19 in the next months will be useful to estimate the percentage of failure to refill truly related to COVID-19 and on the measures adopted. The identification of patients that do not refill their prescriptions allows healthcare professionals to put in place actions aimed to promptly correct the lack of adherence, thus reducing the associated negative outcomes., Competing Interests: The authors report no conflicts of interest in this work., (© 2020 Degli Esposti et al.)

Purpose: To analyze the treatment patterns of psoriatic arthritis (PSA) or ankylosing spondylitis (AS) patients under biological therapies and to evaluate in this population the health-care resource consumption and related costs., Patients and Methods: A retrospective analysis was performed on administrative databases of the Veneto region. Patients ≥18 years with at least one prescription of biological drugs and a diagnosis at any level for PSA or AS from January 1, 2011 to December 31, 2016 (inclusion period) were included. Index date (ID) was defined as date of first biological drug prescription during inclusion period. Patients were characterized the year before ID and followed-up for one year after ID. The drug utilization profile in terms of adherence, persistence and therapeutic regimen changes, and the health-care resource consumption was analyzed during follow-up., Results: A total of 2602 patients were included: 1857 with PSA and 745 with AS. In the PSA cohort, 40.3% of patients were prescribed adalimumab, 35.6% etanercept, 8.0% golimumab, 7.5% infliximab, 5.6% ustekinumab and 3.0% certolizumab. Percentage of PSA patients adherent to treatment was higher among ustekinumab patients (91.3%) and lower among etanercept users (54.3%). Persistence ranged from 53.2% (infliximab) to 70.3% (etanercept). Regarding AS cohort, 45.5% of patients were prescribed adalimumab, 26% etanercept, 17.3% infliximab, 9.7% golimumab and 1.5% certolizumab. Adherence ranged from 46.9% (etanercept) to 90.9% (certolizumab) and persistence from 62.8% (adalimumab) to 81.8% (certolizumab). Mean annual health-care costs (including costs for drug treatment, diagnostic services, specialist visits and hospital admissions) ranged from €9727 (certolizumab) to €14,994 (ustekinumab) among PSA patients and from €9875 (infliximab) to €12,991 (golimumab) among AS patients., Conclusion: This study in Veneto region gave a picture of biological treatment patterns among PSA and AS patients in a real-world setting. Our findings showed the high degree of variability concerning utilization of each biological drug and provided insight on the economic burden of both diseases., Competing Interests: VP, DS, EG, and LDE report no conflicts of interest in relation to this work and are employees of Clicon S.r.l. Clicon S.r.l. is an independent company. The agreement signed by Clicon S.r.l. and Novartis does not create any entityship, joint venture or any similar relationship between parties. Neither CliCon S.r.l. nor any of their representatives are employees of Novartis for any purpose. DR and MN are employees of Novartis Pharma, Origgio, Italy. AMM and MA received scholarship from Novartis., (© 2020 Perrone et al.)

Purpose: To evaluate and compare the incidence of cardiovascular (CV) events in a large contemporary cohort of patients diagnosed with prostate cancer (PCa) and in treatment with GnRH agonists or GnRH antagonists., Patients and Methods: An Italian observational retrospective cohort study based on administrative databases of three local health units and two Regions was performed. PCa patients treated with GnRH agonists or antagonist were included between January 01, 2013 and December 31, 2016. Index date (ID) was the date of first GnRH agonist/antagonist prescription during inclusion period. Follow-up was from ID to December 31, 2017. Patients were excluded if they were under abiraterone treatment or combination therapy with antiandrogens during follow-up. The incidence rate of CV events (acute myocardial infarction, ischemic heart diseases, cerebrovascular diseases, cardiac dysrhythmias, heart failure, atherosclerosis, aneurism, other CV-related conditions) was calculated among patients not switching to androgen deprivation therapy (ADT) in the overall cohort and in a sub-cohort of patients without previous CV events., Results: In total, 9785 (mean age 76.8 ± 8.5) patients were included: 9158 (93.6%) were treated with a GnRH agonist and 627 (6.4%) with a GnRH antagonist. Of them, 9627 did not switch to ADT and were considered in the analyses. The incidence of CV events was significantly higher in patients treated with GnRH agonists rather than antagonists (8.8 vs 6.2, p=0.002). Mean time to CV event was beyond 1 year of treatment in both groups. In the multivariable regression analysis, the risk of experiencing CV events was significantly lower in patients treated with GnRH antagonist rather than those treated with GnRH agonists [HR (95% CI): 0.76 (0.60-0.95), p=0.018]. These findings were confirmed in the sub-cohort of patients without previous CV events., Conclusion: This Italian observational study shows that most patients received a GnRH agonist rather than a GnRH antagonist prescription. GnRH antagonist seems to have a better CV risk profile than GnRH agonist, both in patients with and without a history of CV events., Competing Interests: The views expressed here are those of the authors and not necessarily those of the supporters. The agreement signed by Clicon S.r.l. and Ferring Pharmaceuticals does not create any entityship, joint venture or any similar relationship between parties. Clicon S.r.l. is an independent company. Neither Clicon S.r.l. nor any of their representatives are employees of Ferring Pharmaceuticals for any purpose. MO has worked as a consultant for Ferring and reports personal fees from Ferring, during the conduct of the study; personal fees from Janssen and Takeda, outside the submitted work. The authors report no other conflicts of interest in this work., (© 2020 Perrone et al.)

Objectives: The aim of the study was to assess all-cause mortality and cardiovascular (CV) events in patients after a period of 12 months of treatment with dual antiplatelet therapy (DAPT) after hospitalization for acute myocardial infarction (AMI) in a real-world setting. Health care costs for the management of patients post-AMI was also assessed., Methods: A retrospective analysis using data from the administrative databases of six local health units (LHUs) was performed. All beneficiaries of these LHUs hospitalized with AMI between January 01, 2010, and December 31, 2011, and exposed to a treatment period with DAPT up to 12 months after AMI discharge were included. All-cause mortality, CV hospitalizations, and health care costs occurring during the 36-month follow-up period from end of treatment with DAPT were considered. For the cost analysis, only patients still alive at the end of the follow-up period were included., Results: A total of 2,721 patients were included (mean ± SD age 63.6±17.3 years, 67.8% males). About 17% and 18% of all patients had CV events and died during the follow-up period, respectively. The annual mean cost per patient was €3,523.27. During the follow-up period, 63 patients had a second AMI event; for whom, the mean health care cost per patient was €19,570.70., Conclusion: In a real-world setting in Italy, considering a 36-month follow-up period, all-cause mortality, CV events, and related health care cost of patients hospitalized with an AMI undergoing a 12-month treatment period with DAPT remained relevant. This study suggests that increased efforts aimed at the prevention of recurrent AMI are warranted, as well as an accurate risk stratification in order to improve long-term outcome., Competing Interests: Disclosure L Degli Esposti, V Perrone, C Veronesi, and S Buda are employees of Clicon s.r.l. Health, Economics & Outcomes Research. The authors report no other conflicts of interest in this work.

Objectives: This study aimed to: 1) describe treatment patterns and drug utilization profile (in terms of therapeutic strategy used, switch, persistence and drug consumption variation) among adult patients affected by rheumatoid arthritis (RA), and 2) estimate the health care resource utilization and its associated direct cost for the management of RA patients., Methods: A retrospective cohort analysis, using administrative databases of six Local Health Units in Italy, was performed. All adult patients with a confirmed diagnosis of RA between January 1, 2010 and December 31, 2014 were enrolled. The date of the first RA diagnosis according to the study criteria during the study period represented the index date (ID) for each patient. Patients enrolled were observed from the ID for at least 12 months (follow-up period), and their clinical characteristics were investigated for 12 months prior to the ID., Results: A total of 10,401 patients with a confirmed RA diagnosis were included. Mean age was 63.0 years and 25% were male; 67% of patients were untreated at ID. During the followup period, 67.8% of patients treated with biologic agents were persistent with initial therapy, compared to 45.7% for patients on conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), while 11% of patients treated with biologic agents switched during the follow-up period, compared to 17.6% of csDMARDs-treated ones. At the end of the follow-up period, 14.7% of all patients in the analysis had an increase and 12.6% of them had a decrease in their initial drug consumption. The mean cost per RA patient was €3,743., Conclusion: Our study showed that there is still much that needs to be learned about the prescription of csDMARDs and biologics to RA patients in Italy and to identify areas for future research. The knowledge of RA management in a real-life clinical setting could offer an opportunity to improve the management of RA in Italy., Competing Interests: Disclosure WF is an employee of Eli Lilly & Company, Erl Wood, UK; PLR is an employee of Eli Lilly & Company, Madrid, Spain; and SL, VR and SA are employees of Eli Lilly Italy S.p.a., Italy. VP, LDE, SD, and SB report no conflicts of interest in this work. Clicon S.r.l. is an independent company. The agreement sign by Clicon S.r.l. and Eli Lilly & Company does not create any entityship, joint venture or any similar relationship between parties. Neither CliCon nor any of their representatives are employees of Eli Lilly & Company for any purpose.

Objective: The objectives of this study were to estimate the prevalence of Hepatitis C among six Italian Local Health Units (LHUs), to describe patient and antiviral drug characteristics, and to estimate the health care consumption rates and related costs for the management of patients affected by hepatitis C virus (HCV) infection by using data from routine clinical practice., Methods: We conducted a retrospective study using administrative databases of six Italian LHUs. All patients who had a record related to HCV during the enrollment period (July 1, 2009, to December 31, 2014) and who had at least 6 months of data available prior to the first HCV record were included. The date of the first record related to HCV during the enrollment period was considered as a proxy of diagnosis and used as the index date. Patients were followed from the index date up to 1 year, death, or exiting the database. Using the overall cohort of HCV adult patients as the numerator, we estimated the prevalence of HCV among six LHUs. The denominators were obtained from the National Institute of Statistics (N=1,665,682). We also evaluated descriptive patient's characteristics and treatment patterns, and estimated health care consumption rates and related costs for the management of the HCV patients., Results: A total of 7,550 patients were analyzed, of whom 57% were male with a mean age of 57.6±16.4 years. The prevalence of HCV was estimated to be 0.45% (95% confidence interval 0.44-0.46). During the follow-up period, 78.6% of HCV patients had received no antiviral treatment. The annual health care cost associated with HCV infection was €6,022.7 (±7,922.6) while the cost specific to HCV care was €3,154.6 (±4,972.0)., Conclusion: Our findings showed that, in the Italian real-world setting, only a small proportion of HCV-infected patients received an antiviral treatment. Despite the current low prevalence of HCV, the economic impact of such disease remains high., Competing Interests: Disclosure Cinira Lefevre is an employee of Bristol-Myers Squibb (France) and Carmela Nappi is an employee of Bristol-Myers Squibb S.r.l. (Italy). The authors report no other conflicts of interest in this work.

Objectives: The aims of this study were to assess the prevalence of diagnosed atrial fibrillation (AF), the drug use in patients with AF in terms of antithrombotic (AT) strategies used and the compliance with treatment, and to describe the characteristics of patients affected by AF in relation to treatment., Methods: The data collected were provided from databases of general practitioners (GPs) of the Local Health Unit of Bologna in Italy. From January 1, 2009, to December 31, 2012, all subjects aged ≥18 years followed by the 44 GPs enrolled in the study were evaluated, and the subjects with a diagnosis of AF were included in the analysis., Results: From 2009 to 2012, we identified 1,413 patients with a diagnosis of AF (2.09% of 67,517 patients of the 44 GPs). A total of 1,413 patients with a diagnosis of AF (2.09% of 67,517 patients of the 44 GPs) were enrolled in the study. During the study, 14% of the enrolled patients did not receive any prescription of ATs, 30% and 39.56% were treated only with antiplatelet (AP) agents and oral anticoagulants (OACs), respectively, and 16.28% of the patients received prescriptions for both an OAC and an AP agent; of the patients receiving prescriptions for both, only 4.17% received these therapies at the same time. Among the OAC users, the percentage of patients still on treatment with the index drug during the last 3 months of observation was 76.9%., Conclusion: Our findings emphasize that in an Italian real-world setting, the burden of AF in general population from a public health point of view underscores the need for improvement in utilization of appropriate ATs in patients with known AF., Competing Interests: Disclosure The authors have no conflicts of interest to disclose. The opinions expressed in this article do not necessarily reflect the views of the authors’ institutions.

Objective: The aim of this study was to assess healthcare resource consumption and its associated costs among patients with polycystic kidney disease (PKD) in a real-world setting., Methods: An observational retrospective cohort analysis was conducted using data from the administrative databases of four Italian local health units. Data for patients who were diagnosed with PKD during the inclusion period (January 1, 2010 to December 31, 2012) were extracted. The date on which a patient's first PKD hospitalization occurred during the inclusion period was defined as the index date (ID), and the ID was defined as the date of the first dialysis treatment recorded during the inclusion period for patients undergoing dialysis. Data regarding the clinical characteristics of patients included in the study during the 12 months prior to the ID (pre-ID; characterization period) were collected. All patients were then followed up for the 12 months following the ID (post-ID; follow-up period). Healthcare consumption and its associated costs were analyzed during the follow-up period. All costs are reported in euros (€)., Results: A total of 1,123 patients with PKD were included in this study, 61.9% of whom were male; the mean age of the patients was 57.7±24.5 years. At diagnosis, 11.2% and 1.1% of patients were affected by the dominant and recessive forms of PKD, respectively. Approximately 8% of the included patients were undergoing dialysis at ID (baseline). The incidence of dialysis was fourfold greater among patients with autosomal-dominant PKD (ADPKD) than among the total cohort (33.3% compared with an overall 8.3%). During the follow-up period, the average annual rates of healthcare resource consumption were greater among dialyzed than non-dialyzed patients. The average healthcare expenditures were €45,059.62 and €3,913.89 ( p <0.001) per year for dialyzed and non-dialyzed PDK patients, respectively. Our findings suggest that in the real-world Italian context, consumption of healthcare among patients with PKD has increased at dialysis initiation due to the cost of outpatient specialist healthcare services as well as other costs. Research on the prevention of PKD-related complications and disease progression may help to facilitate a decrease in the costs associated with this condition., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Aim: The objectives of this study were to: 1) analyze the drug utilization pattern among adult psoriasis patients who were newly prescribed with topical medication; and 2) assess their adherence to topical therapy and the possibility of switching to other strategies in the treatment process., Methods: An observational retrospective analysis was conducted based on administrative databases of two Italian local health units. All adult subjects who were diagnosed with psoriasis or who were newly prescribed for topical medication with at least one prescription between January 1, 2010, and December 31, 2014, were screened. Only patients who were "non-occasional users of topical drugs" (if they had at least two prescriptions of topical drugs in a time space of 2 years) were considered for the first and second objectives in the analysis. The date of the first prescription of topical agents was identified as the index date (ID), which was then followed for all time available from ID (follow-up period). The adherence to therapy was assessed on the basis of cycles of treatment covered in the 6 months before the end of the follow-up period. The mean health care costs in patients who switched to disease-modifying antirheumatic drugs (DMARDs) or biologics after the ID were evaluated., Results: A total of 17,860 patients with psoriasis who were newly prescribed for topical medication were identified. A total of 2,477 were identified as "non-occasional users of topical drugs", of whom 70.2% had a prescription for a topical fixed combination regimen at ID. Around 19% adhered to their medication, whereas 6% switched to other options of psoriasis treatment. Multivariable logistic regression model shows that patients on fixed combination treatment were less likely to be non-adherent to treatment and less likely to switch to other treatments. The annual mean pharmaceutical costs were €567.70 and €10,606.10 for patients who switched to DMARDs and biologics, respectively., Conclusion: Our findings show that the use of fixed combination topical treatment can lead to improve the likelihood of patients being adherent to treatment and can decrease the likelihood of switching the treatment to DMARDs or biologics., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Aim: The objective of this study was to evaluate the different outcomes associated with the use of budesonide/formoterol compared to fluticasone/salmeterol in fixed combinations in patients with COPD in a "real-world" setting. The outcomes included exacerbation rates and health care costs., Patients and Methods: An observational retrospective cohort analysis, based on administrative databases of three local health units, was conducted. Patients with at least one prescription of fixed-dose combination of inhaled corticosteroids and long-acting β2-agonists (budesonide/formoterol or fluticasone/salmeterol), at dosages and formulations approved for COPD in Italy, between January 1, 2009 and December 31, 2011 (inclusion period), were included. Patients were followed until December 2012, death or end of treatment (follow-up period), whichever occurred first. Patients were included if they were aged ≥40 years and had at least 6 months of follow-up. Propensity score matching was performed to check for confounding effects. Number of hospitalizations for COPD and number of oral corticosteroid and antibiotic prescriptions during follow-up were analyzed using Poisson regression models. The cost analysis was conducted from the perspective of the National Health System., Results: After matching, 4,680 patients were analyzed, of which 50% were males with a mean age of 64±13 years. In the Poisson regression models, the incidence rate ratio for budesonide/formoterol as compared to fluticasone/salmeterol was 0.84 (95% confidence interval [CI]: 0.74-0.96, P =0.010) for number of hospitalizations, 0.89 (95% CI: 0.87-0.92, P <0.001) for number of oral corticosteroid prescriptions and 0.88 (95% CI: 0.86-0.89, P <0.001) for number of antibiotic prescriptions. The mean annual expenditure for COPD management was €2,436 for patients treated with budesonide/formoterol and €2,784 for patients treated with fluticasone/salmeterol., Conclusion: Among patients with COPD, treatment with a fixed combination of budesonide/formoterol was associated with fewer exacerbations and a lower, but not significant, cost of illness than the treatment with fluticasone/salmeterol. Real-world analyses are requested to ameliorate interventions to address unmet needs, optimizing treatment pathways to improve COPD-related burden and outcomes., Competing Interests: The authors report no conflicts of interest in this work.

Introduction: The objective of this study was twofold: 1) to assess the residual cardiovascular (CV) risk among patients treated with statins according to guidelines and at the recommended dosages; and 2) to assess the difference, if any, in the frequency of CV events when patients were treated with other lipid-lowering agents alongside statins., Methods: A retrospective observational study including one local health unit was conducted. Administrative databases were linked to laboratory test database in order to collect cholesterol values at baseline. Patients were included if they had filled at least one prescription for statins between January 1, 2009 and December 31, 2011; patients' records were considered for a 12-month time span., Results: A total of 27,330 patients treated with statins were included (50% male, mean age 68.0±11.5 years). Among them, 770 were treated with statins according to guidelines and at the recommended dosages and had a low density lipoprotein-cholesterol value below the therapeutic target. Nevertheless, the risk of myocardial infarction or stroke remained: incidence rates were 1.3±1.0 per patient per year for moderate CV risk, 4.1±2.6 for high risk, and 12.5±11.0 for very high risk. This incremental risk was confirmed further using the Cox model, by correcting for age, sex, use of antiplatelet and/or antihypertensive therapy, and adherence to treatment. As a second analysis, we compared, after a propensity score matching, patients extracted from the overall sample who were treated with fibrates. Based on the Cox model, patients on fibrates had a risk for myocardial infarction or stroke lower than patients on statins., Conclusion: Among patients treated with statins according to guidelines and at the recommended dosages, a residual CV risk was observed. We concluded that intervention for managing residual CV risk during statin therapy should be implemented., Competing Interests: The authors report no conflicts of interest in this work.

Introduction: Hepatitis C virus (HCV) infection represents serious health problems worldwide and is a major contributor to end-stage liver disease including cirrhosis and hepatocellular carcinoma (HCC). In Italy, ~2% of subjects are infected with HCV. The objective of this study was to describe treatment patterns, disease progression, and resource use in HCV., Methods: An observational retrospective cohort analysis based on four Local Health Units administrative and laboratory databases was conducted. HCV-positive patients between January 1, 2009 and December 31, 2010 were included and followed-up for 1 year. To explore which covariates were associated to disease progression (cirrhosis, HCC, death for any cause), Cox proportional hazards models were performed., Results: A total of 9,514 patients were analyzed of which 55.6% were male, aged 58.1±16.1, and prevalence 0.4%; 5.8% were positive to human immunodeficiency virus (HIV) infection, 3.0% to hepatitis B virus (HBV), and 1.6% to HCV+HBV+HIV; 26.1% had cirrhosis and 4.3% HCC. The majority of patients (76%) did not receive an antiviral treatment; the main factors affecting this decision were age, 44.1% of untreated patients being aged >65 years; 31% were affected by cirrhosis, 6.6% had ongoing substance or alcohol abuse, and 5.5% were affected by HCC. Disease progression in the observed timeframe was less frequent among treated patients (incidence rate per 100 patients/year: cirrhosis 2.1±0.7 vs 13.0±1.0, HCC 0.5±0.3 vs 3.6±0.5, death 0.5±0.3 vs 6.4±0.7). The annual expenditure for HCV management (drugs, hospitalizations, outpatient services) was €4,700 per patient., Conclusion: This observational, real-life study shows that only a small proportion of patients received antiviral therapy in the territorial services investigated; among patients who were not treated, this is reflected in a disease progression and cost of management higher than treated patients. These results suggest the importance of better defining the categories of patients who can really postpone treatment, and those who require immediate antiviral therapy., Competing Interests: The authors report no conflicts of interest in this work.

Objective: The purpose of this study was to determine the prevalence of adverse drug reactions (ADRs) reported in emergency departments (EDs) and carry out a thorough characterization of these to assess preventability, seriousness that required hospitalization, subsequent 30-day mortality, and economic burden., Methods: This was a retrospective cohort study of data from an active pharmacovigilance project at 32 EDs in the Lombardy region collected between January 1, 2010 and December 31, 2011. Demographic, clinical, and pharmacological data on patients admitted to EDs were collected by trained and qualified monitors, and deterministic record linkage was performed to estimate hospitalizations. Pharmacoeconomic analyses were based on Diagnosis-Related Group reimbursement., Results: 8,862 ADRs collected with an overall prevalence rate of 3.5 per 1,000 visits. Of all ADRs, 42% were probably/definitely preventable and 46.4% were serious, 15% required hospitalization, and 1.5% resulted in death. The System Organ Classes most frequently associated with ADRs were: skin and subcutaneous tissue, gastrointestinal, respiratory thoracic and mediastinal, and nervous system disorders. The most common Anatomical Therapeutic Chemical classes involved in admissions were J (anti-infectives and immunomodulating agents), B (blood and blood-forming organs), and N (nervous system). Older age, yellow and red triage, higher number of concomitantly taken drugs, and previous attendance in ED for the same ADR were significantly associated with an increased risk of hospitalization. The total cost associated with ADR management was €5,184,270, with a mean cost per patient of €585. Fifty-eight percent of the economic burden was defined as probably/definitely preventable., Conclusion: ADRs are a serious health/economic issue in EDs. This assessment provides a thorough estimation of their seriousness, preventability, and burden impact in a large population from a representative European region.

Objectives: Systemic administration of anti-tumor necrosis factor alpha (anti-TNF alpha) leads to an anti-inflammatory and joint protective effect in pathologies such as rheumatoid arthritis, psoriasis, and Crohn's disease. The aim of this study was to assess adherence to therapy, persistence in treatment (no switches or interruptions), and consumption of care resources (drugs, outpatient services, hospitalizations)., Methods: We conducted an observational retrospective cohort analysis using the administrative databases of five local health units. Patients filling at least one prescription for anti-TNF alpha between January 1, 2009 and December 31, 2011 were included and followed up for 1 year. Patients were defined as adherent if >80% of the follow-up period was covered by drugs dispensation., Results: A total of 1,219 patients were analyzed (mean age 49.6±14.6, male 47%). Among enrolled patients, 36% were affected by rheumatoid arthritis, and 31% and 10% were affected by psoriasis and Crohn's disease, respectively; other indications remained below these percentages. Thirty-four percent of patients (420) were treated with adalimumab, 51% (615) with etanercept, and 15% (184) with infliximab. Among the 94% of patients who did not switch, those treated with infliximab had a higher rate of adherence across all indications (51% overall) when compared to that observed in patients treated with etanercept (27%) or adalimumab (23%). The mean annual nonpharmacological expenditure for each patient in analysis was €988 for adherent and €1,255 for nonadherent patients. Infliximab was associated with the lowest cost for all indications as determined by the multivariate generalized linear model., Conclusions: Patients treated with infliximab were associated with higher adherence and persistence in treatment and lower costs, as compared to those treated with adalimumab or etanercept.

Background: Highly active antiretroviral therapy (HAART) has reduced morbidity and mortality in patients infected with human immunodeficiency virus (HIV). Studies have documented high interindividual variability in the pharmacokinetics of antiretroviral drugs, which may impair the success of HAART if not managed properly. Therapeutic drug monitoring (TDM) is a useful diagnostic tool that helps clinicians to optimize drug doses so that drug concentrations associated with the highest therapeutic efficacy are obtained with a reduced risk of concentration-dependent adverse effects. The aim of this study was to assess whether use of TDM improves clinical outcomes and cost of illness., Methods: A retrospective cohort study was conducted at L Sacco University Hospital in Milan, Italy, in HIV-infected patients aged ≥18 years with at least one prescription of antiretroviral drugs for which TDM was applied. The inclusion period was from January 2010 to December 2011, with a follow-up period of up to 12 months. Laboratory and administrative databases were analyzed and matched with each other., Results: The cohort consisted of 5,347 patients (3,861 males and 1,486 females) of mean age 43.9±12.5 years. We found that TDM had been used in 143 of these patients, among whom adherence with therapy was significantly higher than among those in whom TDM had not been used (94% versus 78%). In TDM-controlled patients, the mean length of HIV-related hospitalization stay and mean cost of hospitalization were significantly reduced with respect to those observed in the group in which TDM had not been used (7.21 days versus 29.47 days and €293 versus €688, respectively)., Conclusion: Inclusion of TDM as part of routine clinical optimization of drug dosing in HIV-infected patients is associated with higher adherence to therapy, reduced length of hospitalization stay, and reduced cost of illness.