Iron therapy supplementation in inflammatory bowel disease patients with iron deficiency anemia: findings from a real-world analysis in Italy.

BACKGROUND: This real-world analysis evaluated iron therapy supplementation in inflammatory bowel disease patients with iron-deficiency anemia, considering disease progression and healthcare resource consumption. METHODS: A retrospective observational study was conducted using administrative databases of a pool of Italian healthcare entities, covering about 9.3 million beneficiaries. Between January 2010 and September 2017, adult patients were enrolled in the presence of either hospitalization or active exemption code for ulcerative colitis/Crohn's disease, or one vedolizumab prescription. Iron-deficiency anemia was identified by at least one prescription for iron and/or hospitalization for iron-deficiency anemia and/or blood transfusion (proxy of diagnosis). Patients were divided in untreated and iron-treated during 12-month follow-up and analyzed before and after propensity score matching. Disease progression, was evaluated through inflammatory bowel disease-related hospitalizations and surgeries, and healthcare resource utilization was assessed. RESULTS: Overall, 1753 patients were included, 1077 (61.4%) treated with iron therapy and 676 (38.6%) untreated. After propensity score matching, 655 patients were included in each group. In unbalanced cohorts, disease progression was significantly reduced in patients receiving iron therapy compared to the untreated (11.0% vs. 15.7%, P  < 0.01), and this trend was maintained also after applying propensity score matching. The overall mean cost/patient was significantly lower in iron-treated than untreated (4643€ vs. 6391€, P  < 0.01). CONCLUSION: The findings of this real-world analysis suggest that iron therapy was associated with significant benefits in inflammatory bowel disease patients with iron-deficiency anemia, in terms of both disease progression and healthcare resource utilization.

Profile, Healthcare Resource Consumption and Related Costs in ANCA-Associated Vasculitis Patients: A Real-World Analysis in Italy.

INTRODUCTION: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are rare autoimmune diseases triggering inflammation of small vessels. This real-world analysis was focused on the most common AAV forms, granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), to describe patients' demographic and clinical characteristics, therapeutic management, disease progression, and the related economic burden. METHODS: A retrospective analysis was conducted on administrative databases of a representative sample of Italian healthcare entities, covering approximately 12 million residents. Between January 2010 and December 2020, adult GPA patients were identified by payment waiver code or hospitalization discharge diagnosis, and MPA patients by payment waiver code with or without hospitalization discharge diagnosis. Clinical outcomes were evaluated through AAV-related hospitalizations, renal failure onset, and mortality. Economic analysis included healthcare resource utilization deriving from drugs, hospitalizations, and outpatient specialist services. The related mean direct costs year/patient were also calculated in patients stratified by presence/absence of glucocorticoid therapy and type of inclusion criterion (hospitalization/payment waiver code). RESULTS: Overall, 859 AAV patients were divided into GPA (n = 713; 83%) and MPA (n = 146; 17%) cohorts. Outcome indicators highlighted a clinically worse phenotype associated with GPA compared to MPA. Cost analysis during follow-up showed tendentially increased expenditures in glucocorticoid-treated patients versus untreated (overall AAV: €8728 vs. €7911; GPA: €9292 vs. €9143; MPA: €5967 vs. €2390), mainly driven by drugs (AAV: €2404 vs. €874; GPA: €2510 vs. €878; MPA: €1881 vs. €854) and hospitalizations. CONCLUSION: Among AAV forms, GPA resulted in a worse clinical picture, higher mortality, and increased costs. This is the first real-world pharmaco-economic analysis on AAV patients stratified by glucocorticoid use on disease management expenditures. In both GPA and MPA patients, glucocorticoid treatment resulted in higher healthcare costs, mostly attributable to medications, and then hospitalizations, confirming the clinical complexity and economic burden for management of patients with autoimmune diseases under chronic immunosuppression.

Characteristics and Drug Utilization of Patients with Hereditary Angioedema in Italy, a Real-World Analysis.

This real-world analysis investigated the characteristics and treatment patterns of patients with hereditary angioedema (HAE) in Italy using the administrative data of health units across Italy. Patients were identified via exemption code or HAE-specific treatments (thus, all known forms, type I, II and, III, were included). The index date was that of first prescription of HAE treatments within the inclusion period (01/2010-06/2021) or of the date of exemption. The number of HAE patients included was 148 (43.2% male, mean age 43.3 years). Gastrointestinal disorders affected 36.5% patients, hypertension affected 28.4%, hypercholesterolemia affected 11.5%, and depression affected 9.5%. The frequent gastrointestinal involvement was further confirmed by the use of antiemetics and systemic antihistamines that doubled after the index date. Among patients enrolled by treatment (n = 125), n = 105 (84%) were receiving a treatment for acute attacks. This analysis provided insights into the characterization of patients with HAE and their management in Italian clinical practice, suggesting that an unmet therapeutic need could be present for such patients in terms of the clinical burden.

Iron deficiency anemia impacts disease progression and healthcare resource consumption in patients with inflammatory bowel disease: a real-world evidence study.

Background: Iron deficiency anemia (IDA) is a common extraintestinal manifestation of inflammatory bowel disease (IBD), affecting around one-third of patients. Objective: To compare IBD progression and healthcare resource utilization in patients with and without a co-diagnosis of IDA in a real-world setting. Design: A retrospective comparative study was conducted using Italian entities' administrative databases, covering 9.3 million health-assisted individuals. Methods: Adult IBD patients diagnosed with ulcerative colitis and/or Crohn's disease were enrolled between January 2010 and September 2017. Within 12 months from IBD diagnosis, IDA was identified by at least one prescription for iron and/or IDA hospitalization and/or blood transfusion (proxy of diagnosis). IBD population was divided according to the presence/absence of IDA. Given the nonrandom patients' allocation, propensity score matching (PSM) was applied to abate potential unbalances between the groups. Before and after PSM, IBD progression (in terms of IBD-related hospitalizations and surgeries), and healthcare resource costs were assessed. Results: Overall, 13,475 IBD patients were included, with an average age at diagnosis of 49.9 years, and a 53.9% percentage of male gender. Before PSM, 1753 (13%) patients were IBD-IDA, and 11,722 (87%) were IBD-non-IDA. Post-PSM, 1753 IBD-IDA patients were matched with 3506 IBD-non-IDA. Before PSM, IBD progression was significantly higher in IBD-IDA (12.8%) than in IBD-non-IDA (6.5%) (p < 0.001). After PSM, IBD progression and IBD-related hospitalizations were significantly (p < 0.001) more frequent in IBD-IDA patients (12.8% and 12.0%, respectively) compared to IBD-non-IDA (8.7% and 7.7%). Consistently, healthcare expenditures resulted significantly higher among IDA patients (p < 0.001), with an overall mean annual cost of €5317 compared to €2798 for patients without IDA. These results were confirmed after PSM matching, as the mean annual total cost/patient in IBD-IDA versus IBD-non-IDA were €3693 and €3046, respectively (p < 0.001). Conclusion: In a real-life setting, IDA co-diagnosis in IBD patients was associated with disease progression and higher related economic burden.

Epidemiology, Patients' Journey and Healthcare Costs in Early-Stage Non-Small-Cell Lung Carcinoma: A Real-World Evidence Analysis in Italy.

This real-world analysis aims to estimate the epidemiology and economic burden related to early-stage non-small-cell lung carcinoma (eNSCLC) in the clinical practice Italian setting. An observational analysis was performed using administrative databases linked to pathological anatomy data, covering around 2.5 mln health-assisted individuals. From 2015 to mid-2021, eNSCLC patients staged II-IIIA treated with chemotherapy after surgery were included. Patients were stratified into those presenting loco-regional or metastatic recurrence during follow-up and annualized healthcare direct costs covered by the Italian National Health System (INHS) were estimated. In 2019-2020, the prevalence of eNSCLC was 104.3-117.1/million health-assisted subjects, and the annual incidence was 38.6-30.3/million. Data projected to the Italian population estimated 6206 (2019) and 6967 (2020) prevalent and 2297 (2019) and 1803 (2020) incident cases. Overall, 458 eNSCLC patients were included. Of them, 52.4% of patients had a recurrence (5% loco-regional-recurrence, 47.4% metastatic-recurrence). Healthcare total direct costs/patient averaged EUR 23,607, in particular, in the first year after recurrence, costs averaged EUR 22,493 and EUR 29,337 in loco-regional and metastatic-recurrence patients, respectively. This analysis showed that about one-half of eNSCLC patients stage II-IIIA experience a recurrence, and in recurrence patients, total direct costs were almost two-fold those of no-recurrence patients. These data highlighted an unmet clinical need, as the therapeutic optimization of patients at early stages.

Healthcare Resource Consumption and Related Costs in Patients on Antiretroviral Therapies: Findings from Real-World Data in Italy.

This real-world analysis conducted on administrative databases of a sample of Italian healthcare entities was aimed at describing the role of therapeutic pathways and drug utilization in terms of adherence, persistence, and therapy discontinuation in HIV-infected patients under antiretroviral therapies (ART) and Tenofovir Alafenamide (TAF)-based regimens on healthcare resource consumption and related direct healthcare costs. Between 2015 and 2019, adults (≥18 years) prescribed with TAF-based therapies were identified and characterized in the year prior to the first prescription (index-date) for TAF-based therapies and followed-up until the end of data availability. Overall, 2658 ART-treated patients were included, 1198 of which were under a TAF-based regimen. TAF-based therapies were associated with elevated percentages of adherence (83.3% patients with proportion of days covered, PDC > 95% and 90.6% with PDC > 85%) and persistence (78.5%). The discontinuation rate was low in TAF-treated patients, ranging from 3.3% in TAF-switchers to 5% in naïve. Persistent patients had lower overall mean annual healthcare expenditures (EUR 11,106 in persistent vs. EUR 12,380 in non-persistent, p = 0.005), and this trend was statistically significant also for costs related to HIV hospitalizations. These findings suggest that a better therapeutic management of HIV infection might result in positive clinical and economic outcomes.

Italian Real-World Analysis of the Impact of Polypharmacy and Aging on the Risk of Multiple Drug-Drug Interactions (DDIs) in HCV Patients Treated with Pangenotypic Direct-Acting Antivirals (pDAA).

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.

Trends and determinants of epinephrine prescriptions: a proxy of anaphylaxis epidemiology?

PURPOSE OF REVIEW: Epinephrine autoinjectors (EAIs) are recommended to all patients previously experiencing anaphylaxis reaction in order to prevent further reactions and fatalities. Under that perspective, EAI prescription could be considered as a proxy of anaphylaxis epidemiology. Nevertheless EAI prescription rates are still unacceptably low. RECENT FINDINGS: The review focuses on potential determinants, in addition to clinical indications, which might impact EAI prescription rates by exploring the scientific literature published within the past 18 months, wherever available. Although some controversial results, age, sex, ethnicity, geographical setting and socioeconomic conditions might influence both physician prescription behaviour and EAIs' accessibility from the patient's side, which hampers the accuracy of EAI prescription as a proxy of anaphylaxis. Low EAI prescription and refill rates have been recorded even in the absence of significant socioeconomic barriers, suggesting that economical limitations only partially account for the issue, and cultural restrictions have also to be considered and addressed. SUMMARY: In addition to providing the same opportunities in terms of EAI availability in all countries worldwide, implementing the resources for anaphylaxis management in terms of practical knowledge, education, and allergy specialist networks is an urgent need, even in the absence of socioeconomic barriers.

Analysis of Patients with Focal Epilepsy and Drug-Resistant Epilepsy in Italy: Evaluation of Their Characteristics, Therapeutic Pathway and the Consumption of Healthcare Resources.

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.

Evaluation of the Therapeutic Pattern and Pharmaco-Utilization in Hypercholesterolemic Patients Treated with Statins: A Retrospective Study on Italian Real-World Data.

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.

Real-World Evaluation of Calcimimetics for the Treatment of Secondary Hyperparathyroidism in Chronic Kidney Disease, in an Italian Clinical Setting.

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.

Direct Healthcare Costs by Level of Adherence of a Real-World Population of Statin Users in Italy.

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.

The Use of Oral Amino-Bisphosphonates and Coronavirus Disease 2019 (COVID-19) Outcomes.

The determinants of the susceptibility to severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection and severe coronavirus disease 2019 (COVID-19) manifestations are yet not fully understood. Amino-bisphosphonates (N-BPs) have anti-inflammatory properties and have been shown to reduce the incidence of lower respiratory infections, cardiovascular events, and cancer. We conducted a population-based retrospective observational cohort study with the primary objective of determining if oral N-BPs treatment can play a role in the susceptibility to development of severe COVID-19. Administrative International Classification of Diseases, Ninth Revision, Clinical ModificationI (ICD-9-CM) and anatomical-therapeutic chemical (ATC) code data, representative of Italian population (9% sample of the overall population), were analyzed. Oral N-BPs (mainly alendronate and risedronate) were included in the analysis, zoledronic acid was excluded because of the low number of patients at risk. Incidence of COVID-19 hospitalization was 12.32 (95% confidence interval [CI], 9.61-15.04) and 11.55 (95% CI, 8.91-14.20), of intensive care unit (ICU) utilization because of COVID-19 was 1.25 (95% CI, 0.38-2.11) and 1.42 (95% CI, 0.49-2.36), and of all-cause death was 4.06 (95% CI, 2.50-5.61) and 3.96 (95% CI, 2.41-5.51) for oral N-BPs users and nonusers, respectively. Sensitivity analyses that excluded patients with prevalent vertebral or hip fragility fractures and without concomitant glucocorticoid treatment yielded similar results. In conclusion, we found that the incidence of COVID-19 hospitalization, intensive care unit (ICU) utilization, and COVID-19 potentially related mortality were similar in N-BPs-treated and nontreated subjects. Similar results were found in N-BPs versus other anti-osteoporotic drugs. We provide real-life data on the safety of oral N-BPs in terms of severe COVID-19 risk on a population-based cohort. Our results do not support the hypothesis that oral N-BPs can prevent COVID-19 infection and/or severe COVID-19; however, they do not seem to increase the risk. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Healthcare Resource Consumption and Related Costs of Patients Estimated with Treatment-Resistant Depression in Italy.

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.

Improving statin treatment strategies to reduce LDL-cholesterol: factors associated with targets' attainment in subjects with and without type 2 diabetes.

BACKGROUND: This cross-sectional study aimed to identify actionable factors to improve LDL-cholesterol target achievement and overcome underuse of lipid-lowering treatments in high- or very-high-cardiovascular risk patients. METHODS: We evaluated healthcare records of 934,332 subjects from North-Italy, including subjects with available lipid profile and being on statin treatments up to December 2018. A 6-month-period defined adherence with proportion-of-days-covered ≥ 80%. Treatment was classified as high-intensity-statin (HIS) + ezetimibe, HIS-alone, non-HIS (NHIS) + ezetimibe or NHIS alone. RESULTS: We included 27,374 subjects without and 10,459 with diabetes. Among these, 30% and 36% were on secondary prevention, respectively. Adherence was high (78-100%) and increased with treatment intensity and in secondary prevention. Treatment intensity increased in secondary prevention, but only 42% were on HIS. 2019-guidelines LDL-cholesterol targets were achieved in few patients and more often among those with diabetes (7.4% vs. 10.7%, p < 0.001). Patients in secondary prevention had mean LDL-cholesterol levels aligned slightly above 70 mg/dl (range between 68 and 73 mg/dl and between 73 and 85 mg/dl in patients with and without diabetes, respectively). Moreover, the differences in mean LDL-cholesterol levels observed across patients using treatments with well-stablished different LDL-lowering effect were null or much smaller than expected (HIS vs. NHIS from - 3 to - 11%, p < 0.001, HIS + ezetimibe vs. HIS-from - 4 to + 5% n.s.). These findings, given the observational design of the study, might suggest that a "treat to absolute LDL-cholesterol levels" approach (e.g., targeting LDLc of 70 mg/dl) was mainly used by physicians rather than an approach to also achieve the recommended 50% reduction in LDL-cholesterol levels. Our analyses suggested that female sex, younger age, higher HDL-c, and elevated triglycerides are those factors delaying prescription of statin treatments, both in patients with and without diabetes and in those on secondary prevention. CONCLUSIONS: Among patients on statin treatment and high adherence, only a small proportion of patients achieved LDL-cholesterol targets. Late initiation of high-intensity treatments, particularly among those with misperceived low-risk (e.g., female subjects or those with high HDL-cholesterol), appears as pivotal factors needing to be modified to improve CVD prevention.

Italian Real-World Analysis of a Tyrosine Kinase Inhibitor Administration as First- or Second-Line of Therapy in Patients with Chronic Myeloid Leukemia.

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.

Treatment patterns, health resource consumption, and costs of patients with migraine in an Italian real-world setting.

OBJECTIVE: This study aimed to describe the demographic and clinical characteristics of migraineurs prescribed ≥1 migraine prophylactic therapy, and to analyze their therapeutic pathways, healthcare resource consumption, and related costs. METHODS: This retrospective analysis was based on administrative databases from two regions and three local health units in Italy. Adult patients with ≥1 discharge diagnosis for migraine or ≥1 prescription for migraine-specific drugs, or ≥1 emergency room visit for migraine from 1 January 2010 to 31 December 2016 were included if they had received ≥1 migraine prophylactic therapy between 1 January 2011 and 31 December 2015 (enrollment period). The first date of the last migraine prophylactic treatment was considered as the index date (ID). Patients were characterized 1-year prior ID and followed-up for 1 year afterwards. RESULTS: Of the 166,362 identified migraineurs, 32,794 (mean age: 45.9 ± 13.9 years, 19.2% male) who received migraine prophylaxis were included in the analysis. At ID, 31,629 patients had received 1 prophylactic treatment with antidepressants (51.2%), neuromodulators (28.1%), beta blockers (12.4%), other migraine preparations (7.8%), and botulinum toxin A (0.5%). Focusing on patients with one prophylactic treatment at ID, 85.4% did not have any previous therapeutic failures whereas 14.6% had ≥1 previous failure. During follow-up, 5% of patients made a therapeutic switch after a mean period of 103.4 ± 97.9 days. Total mean annual cost for patients receiving migraine prophylaxis was 1193.64€ during characterization and 1303.86€ during follow-up periods. CONCLUSION: This real-world study gave insights on the characterization of migraineurs and patterns of prophylaxis utilization in Italian clinical settings, showing an underuse of prophylactic agents.

Pharmaco-utilization of biologic drugs in patients affected by psoriasis, psoriatic arthritis and ankylosing spondylitis in an Italian real-world setting.

BACKGROUND: As primary aim the study evaluated the monthly average dose for biologic drugs used for psoriasis (PSO), psoriatic arthritis (PsA) and ankylosing spondylitis (AS) in real-world settings. METHODS: This retrospective analysis was based on administrative databases of Italian Entities. Adult patients diagnosed PSO, PsA or AS with ≥1 prescription of biologic drugs indicated for these diseases were included during 01/01/2011 - 30/06/2017. Monthly average dose and persistence were evaluated during 6-months after inclusion (follow-up). RESULTS: Overall, 6,179 patients prescribed biologic drugs were included: 2,373 represented the 1.1% of PSO-patients, 2,756 the 37.4% of PsA-patients, 1,050 the 17.8% of AS-patients. Monthly average dose was: 69 mg (PSO), 73 mg (PsA), 70 mg (AS) for adalimumab; 152 mg (PSO), 155 mg (PsA), 147 mg (AS) for etanercept; 140 mg (PSO), 133 mg (PsA), 166 mg (AS) for infliximab; 255 mg (PSO), 183 mg (PsA), 154 mg (AS) for secukinumab. Persistance to adalimumab was 76%(PSO), 78%(PsA), 74%(AS); with etanercept 77% in each disease-cohort; with infliximab 67%(PSO), 71%(PsA), 88%(AS); with secukinumab 91%(PSO) and 85%(PsA). CONCLUSION: The study described real-world dosing patterns of biologics indicated for PSO, PsA, or AS, suggesting a trend of monthly average dose generally lower than the dosage indicated in the datasheet.

Treatment Pattern Analysis and Health-care Resource Consumption on Patients with Psoriatic Arthritis or Ankylosing Spondylitis Treated with Biological Drugs in a Northern Italian Region.

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.

Low adherence to inhaled corticosteroids/long-acting ß2-agonists and biologic treatment in severe asthmatics.

Less than half of severe asthmatic patients show a >80% adherence rate to inhaled treatment just before and during biologic therapy. This has implications in biologic treatment sustainability and disease prevalence estimation. http://bit.ly/3cRTJB0.