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Enrico Torre,1 Sergio Di Matteo,2 Chiara Martinotti,2 Giacomo Matteo Bruno,3 Umberto Goglia,4 Gianni Testino,5 Alberto Rebora,1 Luigi Carlo Bottaro,6 Giorgio Lorenzo Colombo3 1Diabetology and Metabolic Diseases Unit - ASL3, Genoa, Italy; 2Center of Research, SAVE Studi - Health Economics and Outcomes Research, Milan, Italy; 3Department of Drug Sciences, University of Pavia, Pavia, Italy; 4Territorial Diabetology Unit, ASLCN1, Cuneo, Italy; 5Units of Addiction and Hepatology, ASL3, Genoa, Italy; 6General Direction, ASL3, Genoa, ItalyCorrespondence: Giorgio Lorenzo Colombo, Email giorgio.colombo@unipv.itBackground: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a multisystem condition destined to become pandemic in the coming decades. This study aimed at evaluating the economic impact of MASLD in the Italian population from the Italian National Healthcare Service (NHS) perspective.Methods: The economic impact of the MASLD was assessed by developing a calculation model in Microsoft Excel® from the Italian NHS perspective, considering healthcare resources and direct costs. The target population was based on the prevalence data. Through a literature search, complications of MASLD were identified, including MASH, with relative risk of evolution into CC, DCC, HCC, T2DM, cardiovascular diseases, in particular AMI and stroke, CKD, and CRC. The differential impact between complication development in the population with MASLD and the same sample size population without-MASLD was evaluated. Differential risk data, mortality rates, and event unit costs were drawn from the published international literature. Frequency and cost data were applied to the total target population, the total annual costs and mortality data, referring to the two arms, were then calculated, and the differential value was obtained.Results: Based on an estimated 11,546,370 MASLD target population, an annual illness impact of € 12,251,631,822 was calculated, corresponding to a difference of € 7,731,674,054 compared with the same sample size without MASLD. Moreover, the MASLD population is expected to experience 13,438 additional deaths annually.Conclusion: The growing epidemiological impact of MASLD and its complications represent a huge economic burden for healthcare services worldwide. An integrated approach, including changes in lifestyle behaviors, will be the first step. Specific drugs for MASLD are not yet available; however, studies are underway, and combined pharmaceutical therapies may be an inevitable choice to achieve adequate control of MASLD and its complications.Keywords: metabolic associated fatty liver disease MASLD, complications, MASLD burden in Italy, healthcare costs, treatment and perspectives

Francesco Pesce,1 Giacomo Matteo Bruno,2 Giorgio Lorenzo Colombo,2 Sergio Di Matteo,3 Anna Rita Maurizi,4 Valentina Mongelli,4 Silvia Mele,5 Lavinia Narici,5 Stefano Bianchi,6 Mario Bonomini,7 Giuseppe Castellano,8 Luca De Nicola,9 Giovanni Gambaro,10 Giuseppe Grandaliano,11 Gaetano La Manna,12 Antonello Pani,13 Andrea Ranghino,14 Loreto Gesualdo15 1Division of Renal Medicine, “Fatebenefratelli Isola Tiberina—Gemelli Isola”, Rome, 00186, Italy; 2Department of Drug Sciences, University of Pavia, Pavia, Italy; 3S.A.V.E. Studi Analisi Valutazioni Economiche, Milan, Italy; 4Cardiovascular, Renal and Metabolism Medical Affairs, AstraZeneca, Milan, Italy; 5Value & Access, AstraZeneca, Milan, Italy; 6Nephrology and Dialysis Unit, Department of Internal Medicine, ASL Toscana Nordovest, Regione Toscana, Livorno, Italy; 7Department of Medicine, Section of Nephrology and Dialysis, G. D’Annunzio University, Chieti, 66013, Italy; 8UOC of Nephrology, Dialysis, and Kidney Transplant, IRCCS Foundation Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy; 9Department of Advanced Medical and Surgical Sciences, Nephrology and Dialysis Unit, University Vanvitelli, Naples, Italy; 10Division of Nephrology and Dialysis, Department of Medicine, University of Verona, Verona, Italy; 11Department of Translational Medicine and Surgery, Università Cattolica Sacro Cuore, Rome, Italy; 12Nephrology Dialysis and Kidney Transplant Unit, IRCCS Azienda Ospedaliero-Universitaria Di Bologna, Bologna, Italy; 13Department of Nephrology and Dialysis, G. Brotzu Hospital, Cagliari, Italy; 14Nephrology, Dialysis and Kidney Transplant Unit, Ospedali Riuniti Ancona, Ancona, Italy; 15Nephrology, Dialysis and Transplantation Unit, Department of Precision and Regenerative Medicine and Ionian Area (Dimepre-J), University of Bari “aldo Moro”, Bari, ItalyCorrespondence: Giorgio Lorenzo Colombo, Email colombog@unipv.itIntroduction: The underdiagnosis of chronic kidney disease (CKD) remains a significant public health concern. The Early chroNic kiDney disease pOint of caRe Screening (ENDORSE) project aimed to evaluate the clinical and economic implications of a targeted training intervention for general practitioners (GPs) to enhance CKD awareness and early diagnosis.Methods: Data on estimated Glomerular Filtration Rate (eGFR) and Urinary Albumin-Creatinine Ratio (uACR) were collected by 53 Italian GPs from 112,178 patients at baseline and after six months. The intervention involved six months of hybrid training provided by 11 nephrologists, which included formal lectures, instant messaging support, and joint visits for complex cases.Results: The results demonstrated a substantial increase in the use of eGFR (+44.7%) and uACR (+95.2%) tests. This led to a 128.9% rise in the number of individuals screened for CKD using the KDIGO classification, resulting in a 62% increase in CKD diagnoses. The intervention’s impact was particularly notable in high-risk groups, including patients with type 2 diabetes, hypertension, and heart failure.Discussion: A budget impact analysis projected cumulative five-year savings of € 1.7 million for the study cohort. When these findings were extrapolated to the entire Italian CKD population, potential savings were estimated at € 106.6 million, highlighting significant cost savings for the national health service. The clinical simulation assumed that early diagnosed CKD patients would be treated according to current indications for dapagliflozin, which slows disease progression.Conclusion: The ENDORSE model demonstrated that targeted training for GPs can significantly improve early CKD detection, leading to better patient outcomes and considerable economic benefits. This approach shows promise for broader implementation to address the underdiagnosis of CKD on a national and potentially international scale. Keywords: eGFR, uACR, awareness, chronic kidney disease, general practice, economic impact, training intervention, early diagnosis

Sergio Di Matteo,1 Roberto Freilone,2 Giacomo Matteo Bruno,1,3 Rosario Notaro,4 Sabrin Moumene,1 Nicoletta Martone,5 Cristina Teruzzi,5 Antonio Ciccarone,1 Giorgio Lorenzo Colombo1,3 1Center of Research, SAVE Studi - Health Economics and Outcomes Research, Milan, Italy; 2Dipartimento di Oncologia - Direttore SC Ematologia, Azienda Ospedaliera Universitaria Città della Salute e della Scienza, Torino e componente Tumor Molecular Board (TMB) Regione Piemonte, Torino, Italy; 3Department of Drug Sciences, University of Pavia, Pavia, Italy; 4Direttore S.C. Core Research Laboratory in ISPRO, Firenze, Italy; 5Sobi S.r.l., Milano, ItalyCorrespondence: Giorgio Lorenzo Colombo, Email giorgio.colombo@unipv.itBackground: Paroxysmal nocturnal hemoglobinuria is a rare, acquired disease characterized by hemolytic episodes and associated with significant clinical burden. The introduction of C5 inhibitory monoclonal antibodies (C5i) represented a major breakthrough in PNH treatment, effectively reducing intravascular hemolysis (IVH) but showing limited impact on extravascular hemolysis (EVH). In 2021, the C3 inhibitor pegcetacoplan was approved by EMA and recently reimbursed in Italy, which also has the advantages in the reduction of both IVH and EVH, increasing hemoglobin values and simultaneously improving the quality of life and fatigue of patients. A cost-utility analysis was developed to compare pegcetacoplan to C5i (eculizumab and ravulizumab) in the PNH population who remain anemic after treatment with C5i for at least 3 months.Materials and Methods: The analysis employed a Markov model with a 5-year time horizon whereby patients can transition among 3 PNH health states, adopting the perspective of the Italian NHS. Efficacy data were sourced from the PEGASUS study, with drug prices reflecting ex-factory costs. Additionally, costs associated with resource utilization, adverse events, and complications were estimated based on outpatient and hospital care rates, excluding indirect expenses. Utility and disutility values related to transfusions were also considered, with pegcetacoplan allowing for dose escalation.Results: The cumulative cost of treatment per individual patient at 5 years was estimated to be € 1,483,454 for pegcetacoplan, € 1,585,763 for eculizumab, and € 1,574,826 for ravulizumab. Pegcetacoplan demonstrated a superior increase in quality-adjusted life years (QALYs) compared to both eculizumab (0.51 increase) and ravulizumab (0.27 increase). Furthermore, pegcetacoplan showed a reduction in complication management costs (€ 22,891 less compared to eculizumab and € 22,611 less compared to ravulizumab) and lower transfusion-related expenses (€ 14,147 less than both C5i treatments).Conclusion: Pegcetacoplan emerged as the dominant strategy in this analysis, being more effective, less expensive and improves quality of life in the analyzed population affected by PNH.Keywords: PNH, pegcetacoplan, eculizumab, ravulizumab, IVH, EVH, cost-utility analysis, pharmacoeconomics

Ivo Abraham,1 Mickael Hiligsmann,2 Kenneth KC Lee,3 Leslie Citrome,4 Giorgio Lorenzo Colombo,5 Mike Gregg6 1University of Arizona, Tucson, AZ, USA; 2Maastricht University, Maastricht, the Netherlands; 3Taylor’s University, Selangor, Malaysia; 4New York Medical College, Valhalla, New York, NY, USA; 5University of Pavia, Pavia, Italy; 6Taylor & Francis, London, SE1 8BF, UKCorrespondence: Mike Gregg, Email mike.gregg@tandf.co.uk

Nanna Nyholm,1 Anne Danø,2 Henrik Schnack,2 Giorgio Lorenzo Colombo3 1LEO Pharma AS, Ballerup, Denmark; 2EY, Frederiksberg, Denmark; 3CEFAT Center of Pharmaceuticals Economics and Medical Technologies Evaluation, Department of Drug Sciences, University of Pavia, Pavia, ItalyCorrespondence: Nanna Nyholm, LEO pharma A/S, Industriparken 55, Ballerup, 2750, Denmark, Tel +45 6178 2096, Email OJYDK@leo-pharma.comObjective: The objective of this study was to optimise the cost-effectiveness of different anti-IL17 treatment sequences used in the treatment of moderate-to-severe plaque psoriasis in Italy and Germany over a five-year time horizon.Methods: We adjusted a previously published treatment sequence model for biologic drugs used in psoriasis treatment to an Italian and German setting, respectively. The model included all anti-IL17 biologics currently available in the treatment of moderate-to-severe plaque psoriasis in the markets of scope (secukinumab, ixekizumab, brodalumab and bimekizumab). Real-world discontinuation rates were used to model switches between the four anti-IL17 biologics included in the study. The treatment costs were based on label dosing recommendations for each drug, including induction and maintenance therapy, and the manufacturer prices of each drug in Italy and Germany, respectively. We used long-term Psoriasis Area and Severity Index 100 (PASI100) measures to inform the model on the efficacy for each treatment. The cost-effectiveness in the analysis was evaluated based on the cost per PASI100-responder.Results: We found that the most cost-effective treatment sequence was achieved by using brodalumab as first-line treatment, bimekizumab as second-line treatment, ixekizumab as third-line treatment and secukinumab as fourth-line treatment in both Italy and Germany, which resulted in a total cost per responder of € 128,200 and € 138,212, respectively, over a five-year period. Several scenario analyses were also conducted and ensured that the results were robust to changes in key input parameters.Conclusion: Our study showed that using brodalumab as a first-line therapy to treat moderate-to-severe psoriasis in both Italy and Germany leads to the most cost-effective treatment sequence, when compared to all possible combinations of anti-IL17s over a five-year time horizon. In addition, we found that treatment discontinuation and switching are important factors when assessing the cost-effectiveness of biologic therapies.Keywords: cost-per-responder, psoriasis vulgaris, treatment sequences, interleukin-17

Giacomo M Bruno,1,2 Maria Chiara Valentino,2 Alessandra Brunetti,3 Sergio Di Matteo,2 Ivan Begovic,2 Edoardo Croce,4 Garifallia Sakellariou,5 Serena Bugatti,6 Pietro Perotti,7 Silvia Vecchio,7 Simona Migliazza,7 Roberto Langella,8 Giorgio L Colombo1,2 1Department of Drug Sciences, Center of Pharmaceuticals Economics and Medical Technologies Evaluation, CEFAT.Unipv - University of Pavia at Centro di Ricerca SAVE Studi, Milano, Italy; 2S.A.V.E. Research Center - Studi Analisi Valutazioni Economiche, Milano, Italy; 3Research and Innovation Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; 4Scientific Direction - IRCCS istituto Ortopedico Galeazzi, Milan, Italy; 5Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy; 6Department of Internal Medicine and Therapeutics, Division of Rheumatology, University of Pavia, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; 7U.O.C. Epidemiological Observatory – Health Protection Agency of Pavia (ATS Pavia), Pavia, Italy; 8SIFO Regional Secretariat - Società Italiana di Farmacia Ospedaliera e dei Servizi Farmaceutici delle Aziende Sanitarie, Milano, ItalyCorrespondence: Giacomo M Bruno, Department of Drug Sciences, Center of Pharmaceuticals Economics and Medical Technologies Evaluation, CEFAT.Unipv - University of Pavia at Centro di Ricerca SAVE Studi, Milano, 20149, Italy, Email giacomomatteo.bruno@unipv.itBackground: The current flows of the SSN represent the set of interest whose interconnection alone justifies the current study. These flows can be interconnected with other sources, institutional or otherwise, in order to answer well-defined questions.Objective: The objective of the study is to verify, through the analysis of administrative databases, any differences in the consumption of health resources between biological off-patent originator drugs and biosimilars in real clinical practice, with particular reference to the rheumatology area.Methods: Through the use of assisted databases (BDA) of ATS Pavia we evaluated the differences in terms of consumption of health resources related to the different drugs under analysis. Annual and daily costs were calculated by total patient cost, stratified for different treatments, considering the sum of total costs for the prescriptions of drugs subject to the analysis. Another objective was to evaluate the adherence of the drugs of interest, by utilizing specific indicators (MPR).Results: A total of 145 patients were analyzed. Among enrolled patients, 26.9% of users were treated with a biosimilar drug, while 73.1% with a biologic originator. Adherence is higher if it is considered the population treated with biosimilar drugs (82.1%). Total cost (including drug prescriptions, hospitalizations, outpatient services, tests for any cause) during the observation period of 1 year is 14,274.08. 87.7% of the total is attributable to drugs. Non-hospitalized patients are the least expensive, whether they were treated with biologics or biosimilars.Conclusion: In our sample, biosimilar drugs tend to be underused: the treatment of a patient with a chronic autoimmune disease is a clinical process that involves many health professionals, and a criticality could also derive from the difficult communication between the various professional figures who get involved with the whole patient treatment.Keywords: real world data, biosimilar, rheumatic diseases, PDTA, EULAR recommendations, rheumatoid arthritis

Giorgio Lorenzo Colombo,1 Maria Chiara Valentino,2 Alessandra Fabi,3 Maria Vittoria Dieci,4,5 Mauro Caruggi,2 Giacomo Matteo Bruno,2 Gloria Lombardi,6 Sergio Di Matteo2 1Department of Drug Sciences, University of Pavia, Pavia, Italy; 2S.A.V.E. Studi Analisi Valutazioni Economiche S.r.l., Health Economics & Outcomes Research, Milan, Italy; 3Precision Medicine Breast Unit, Scientific Directorate, Department of Women, Children and Public Health Sciences, “A. Gemelli” IRCCS, Roma, Italy; 4Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy; 5Oncology 2, Veneto Institute of Oncology IOV-IRCCS, Padova, Italy; 6Real World Solutions, IQVIA Solutions Italy S.r.l, Milan, ItalyCorrespondence: Giorgio Lorenzo Colombo, Email giorgio.colombo@unipv.itBackground: To date, no study evaluated the cost-effectiveness of palbociclib (PAL) plus fulvestrant (FUL) vs ribociclib (RIB) plus FUL and abemaciclib (ABM) plus FUL in Italy. Cost-effectiveness analysis comparing the three cyclin-dependent 4/6 kinase inhibitors in combination with endocrine therapies for the management of postmenopausal women with HR+, HER2- advanced or metastatic breast cancer in Italy was developed.Material and Methods: To assess the cost-effectiveness of PAL plus FUL vs RIB plus FUL and ABM plus FUL, a cost-minimization has been carried out with a conservative scenario considering three CDK4/6 inhibitors with equal effectiveness in terms of overall survival (OS) (MAIC, Rugo et al 2021). Adverse events (AEs) associated with all therapies were obtained from clinical trials. Ad-hoc analysis was performed to estimate the cost-effectiveness considering the quality-of-life (QoL) data (Lloyd et al 2006).Results: Cost-minimization inputs were drugs, visits and exams, AE monitoring and best supportive care (BSC) before the progression state, active and BSC in the progression and terminal phase of the last two weeks of life. Given the comparability of PAL, RIB and ABM in terms of efficacy, this analysis demonstrated slight economic savings over a lifetime for PAL. Results showed saving per patient of € 305 (lifetime) when PAL is compared with RIB; for PAL vs ABM a saving of € 243 (lifetime) in a conservative scenario. Results of a budget impact analysis showed a potential savings of € 319,563 for PAL vs RIB and € 297,544 for PAL vs ABM. When QoL data were considered, results may favor PAL due to the lower impact of AE with savings and improvement in the QoL related to fewer AE.Conclusion: From the Italian perspective, a cost-saving profile associated with the use of PAL+FUL for the management of advanced/metastatic HR+/HER2- breast cancer compared to RIB+FUL and ABM+FUL emerged.Keywords: cost effectiveness, cost-minimization, metastatic breast cancer, palbociclib, ribociclib, abemaciclib, second-line endocrine therapy, Italy

Enrico Torre,1 Sergio Di Matteo,2 Giacomo Matteo Bruno,3 Chiara Martinotti,2 Maria Chiara Valentino,2 Gianni Testino,4 Alberto Rebora,1 Luigi Carlo Bottaro,5 Giorgio Lorenzo Colombo3 1Diabetology and Metabolic Diseases Unit - ASL3, Genoa, Italy; 2S.A.V.E. Studi Analisi Valutazioni Economiche S.r.l., Health Economics & Outcomes Research, Milan, Italy; 3Department of Drug Sciences, University of Pavia, Pavia, Italy; 4Unit of Addiction and Hepatology - ASL3, Genoa, Italy; 5General Direction, ASL3, Genoa, ItalyCorrespondence: Giorgio Lorenzo Colombo, Department of Drug Sciences, School of Pharmacy, University of Pavia, Italy, Email giorgio.colombo@unipv.itBackground: Aim of our study is to evaluate the economic impact of NASH among diabetic population in Italy and potential benefits of treatments that can slow the disease progression.Methods: A Markov model was conducted from the Italian National Healthcare System perspective reporting results at 3, 5, 10 and 15 years. The model included NASH and T2DM patients with all stages of fibrosis (F0-F3), compensated cirrhosis (CC), decompensated cirrhosis (DCC), hepatocellular carcinoma (HCC), liver transplant (LT), post-LT and death. A 1-year model cycle length was considered, with each patient passing through the stages and exiting the model when reached one of mortality states. Transition probabilities and annual cost related to health states were derived from published literature. Moreover, the model made it possible to develop a scenario analysis to simulate the impact of treatments capable of slowing the disease progression in phases F0-F4 (CC).Results: The results highlighted an economic burden of NASH in T2DM patients of approximately € 1.4 billion, € 3.1 billion, and € 9.4 billion, respectively, after 3, 5 and 10 years, reaching about € 17.3 billion after 15 years. The slowing down of the progression in the early stages of the disease (fibrosis F0-CC) has led to significant savings corresponding to € 2.3 billion at 15 years. These savings were generated by the reduction of the patients in the advanced stages of the disease, which is linked to a reduction in deaths, equal to 92,208 deaths avoided over a 15-year time horizon.Conclusion: Patients with NASH and T2DM reported an important burden in Italy. It is important to investigate the potential clinical and economic benefits of antidiabetic drugs that have been shown to be effective in preventing the transition to advanced disease, simultaneously acting on the therapeutic goals of diabetic disease.Keywords: non-alcoholic steatohepatitis, type 2 diabetes mellitus, burden of illness, treatment perspectives

Enrico Torre,1 Giorgio Lorenzo Colombo,2 Sergio Di Matteo,3 Chiara Martinotti,3 Maria Chiara Valentino,3 Alberto Rebora,1 Francesca Cecoli,1 Eleonora Monti,1 Marco Galimberti,4 Paolo Di Bartolo,5 Germano Gaggioli,6 Giacomo Matteo Bruno2 1Endocrinology Diabetology and Metabolic Diseases Unit - ASL3, Genoa, Italy; 2Department of Drug Sciences, University of Pavia, Pavia, Italy; 3S.A.V.E. Studi Analisi Valutazioni Economiche S.r.l., Health Economics & Outcomes Research, Milan, Italy; 4DP Trade SA, Lugano, Switzerland; 5Diabetes Center of Ravenna, Romagna Diabetes Clinical Network, Romagna Local Health Authority, Ravenna, Italy; 6Cardiology Unit Villascassi Hospital - ASL3, Genoa, ItalyCorrespondence: Giorgio Lorenzo ColomboDepartment of Drug Sciences, School of Pharmacy, University of Pavia, Pavia, ItalyEmail giorgio.colombo@unipv.itBackground: In Italy, the adoption of a total lockdown has generated almost total suspension of outpatient visits except for emergencies. Even after lockdown, the pandemic fear created additional barriers to access the health services. The aim of our study is to evaluate the economic impact of the lockdown for COVID-19 on public health in Italy, focusing on its effects on diabetic population.Materials and Methods: We analyzed the impact of the lockdown on excess mortality and morbidity in the Italian diabetic population during 2020. The analysis was divided into several steps: a quantification of specialist visit reduction, the calculation of excess mortality in the diabetic population, the economic evaluation of the slowdown in the use of innovative diabetic therapies. Furthermore, the impact of the lockdown on the reduction of procedures and follow-up visits in diabetic population was evaluated. The overall impact of the pandemic and lockdown effects on costs and quality of life was then calculated.Results: During 2020, a drop of 28% in patient access has been observed. Diabetic patients recorded a twice higher mortality value compared to general population (20.4% vs 10.2%). The analysis of market data revealed a slowdown in consumption of new antidiabetic therapies (− 14%, 27% vs 41%). We estimated an expense of € 26.6 million for NHS and a loss of 257 utilities in diabetic population due to the missed benefits related to slowdown in innovative antidiabetic drugs use and non-optimal follow-up and control of diabetes complications. In simulation scenarios, we also estimated an overall expenditure ranging from € 38.7 to 94.0 million and a loss of 294– 836 utilities.Conclusion: Diabetic population paid a high tribute to pandemic and lockdown, both in terms of number of deaths and burden of diabetic complications, together with an overall deterioration of quality of life.Keywords: COVID-19, diabetes type II, diabetic complications, quality of life, economic impact

Giorgio Lorenzo Colombo,1 Franca Heiman,2 Ilaria Peduto2 1CEFAT - Department of Drug Sciences, University of Pavia, Pavia, Italy; 2Real World Solutions, IQVIA Solutions Italy S.r.l., Milan, ItalyCorrespondence: Ilaria PedutoIQVIA Solutions Italy S.r.l., Via Fabio Filzi 29, Milan, 20124, ItalyEmail ilaria.peduto@iqvia.comPurpose: Understand the demographics and clinical features of patients with osteoarthritis (OA), quantify healthcare resource utilization by OA patients, and estimate the annual direct medical costs per OA patient from a National Health Service (NHS) perspective in Italy.Patients and Methods: Retrospective observational cohort analysis using data from electronic medical records captured by the Italian IQVIA Longitudinal Patient Database (LPD). Only direct medical costs reimbursed by the NHS were considered. Patients were included if they received at least one diagnosis of OA during the period from January 1 to December 31, 2018. Each patient was observed for 3 years: a 24-month baseline period preceding the index date, and a 12-month follow-up period starting at the index date.Results: A total of 71,467 patients met inclusion criteria: 43.98% had not been prescribed NSAIDs/opioids, 40.76% had been prescribed NSAIDs, and 15.26% an opioid. Mean age was 71.36 years, and 68.2% of the patients were women. At least one comorbidity was present in 91.34% of the patients; 38.05% were newly diagnosed with OA. During 1-year of follow-up, 173,884 prescriptions with an associated diagnosis of OA were found: 47.36% had been prescribed an NSAID, 9.11% diclofenac, 8.30% codeine+paracetamol, and 7.32% ketoprofen. Nearly 15% of the patients had at least 1 request for a specialist visit and 23.82% had at least 1 request for exams. Orthopedic visits accounted for 60% of all specialist visits. Yearly mean costs per patient were € 622, for approximately € 2.5 billion per year in direct costs, considering 3.9 million patients with OA in Italy. Protheses were a major driver in annual costs: € 143.45 in patients without a prosthesis and € 10,090.91 in those with a joint prosthesis.Conclusion: This real-world analysis of direct costs of care of patients with OA in Italy confirms the substantial economic burden. Direct costs dramatically increased when joint replacement was needed.Keywords: osteoarthritis, costs, real-world, Italy

Enrico Torre,1 Giacomo M Bruno,2 Sergio Di Matteo,2 Chiara Martinotti,2 Maria Chiara Valentino,2 Luigi C Bottaro,3 Giorgio L Colombo4 1Endocrinology Diabetology and Metabolic Diseases Unit - ASL3, Genoa, Italy; 2S.A.V.E. Studi Analisi Valutazioni Economiche S.r.l., Health Economics & Outcomes Research, Milan, Italy; 3General Direction, ASL3, Genoa, Italy; 4Department of Drug Sciences, School of Pharmacy, University of Pavia, Pavia, ItalyCorrespondence: Giorgio L ColomboDepartment of Drug Sciences, School of Pharmacy, University of Pavia, Pavia, ItalyEmail giorgio.colombo@unipv.itBackground: Diabetes represents a relevant public health problem worldwide due to its growing prevalence and socioeconomic burden, principally due to the development of macrovascular and microvascular complications as well as to the continuous launch of new and even more expensive drugs. The aim of our study is to evaluate the economic impact of dulaglutide, a weekly GLP-1 receptor agonist, on the treatment of diabetic patients as an alternative to both high dose sulphonylureas and insulin basalization at the failure of oral therapies alone. We carried out a cost-effectiveness analysis developed considering the economic implications of recent clinical studies regarding cardiovascular risk drug effects and especially of REWIND studies outcomes, focusing on the impact of weight changes on HRQoL.Material and Method: In our analysis, we have applied the cost-utility technique to the above reported clinical outcomes and compared the global costs of dulaglutide versus sulfonylurea or basal insulin, all in add-on with metformin. We have chosen gliclazide, as a sulfonylurea and Abasaglar®, the less expensive among basal insulin analogues. Abasaglar was titrated to 20 IU, corresponding to the mean dosage used in the treatment of type II diabetic patients. The model aims to estimate total direct costs related to the above-reported treatments and find out the real gap in costs between dulaglutide, the apparently cheaper gliclazide and basal insulin glargine (IGlargine) based on the Italian National Healthcare System (INHS).Results: The total cost of dulaglutide has resulted in € 859.66 higher than gliclazide (€ 1,579.73 vs € 720.07) and basal insulin, although less significantly, reporting a difference of € 396.54 (€ 1,579.73 vs 1,183.19). Except for the purchase cost, dulaglutide has reported reduced costs compared to insulin IGlargine and gliclazide. Dulaglutide showed lower self-monitoring blood glucose and hypoglycaemia costs, a significant reduction in costs related to cardiovascular complications, as well as savings in costs in other drugs. Dulaglutide can be considered a cost-effective antidiabetic therapy, due to the positive impact on the quality of life induced by weight reduction, despite the higher annual cost per patient, mainly influenced by drug purchase cost.Discussion and Conclusion: In this cost-utility analysis, dulaglutide has shown to be a cost-effective treatment option from the Italian healthcare system perspective as add-on therapy to metformin in patients with inadequately controlled type 2 diabetes mellitus. Study findings can provide stakeholders valuable evidence to support the adoption of this cost-effective second- or third-line therapy compared to gliclazide or basal insulin glargine. Dulaglutide cost-effectiveness has been particularly evident in the comparison with basal insulin glargine, indicating that, in patients who have treatment indication, this therapy may be preferred to basalization avoiding related complications and costs.Keywords: dulaglutide, cost utility analysis, diabetes type II

Giorgio Walter Canonica, 1 Giorgio Lorenzo Colombo, 2, 3 Paola Rogliani, 4 Pierachille Santus, 5 Claudia Pitotti, 6 Sergio Di Matteo, 3 Chiara Martinotti, 3 Giacomo Matteo Bruno 3 1Asthma & Allergy Clinic, Humanitas University, Milan, Italy; 2S.A.V.E. S.r.l. Studi Analisi Valutazioni Economiche Health Economics & Outcomes Research - Research Center, Milan, Italy; 3Drug Science Department, Pavia University, Pavia, Italy; 4Respiratory Unit, Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, Rome, Italy; 5Department of Biomedical and Clinical Sciences (DIBIC), University of Milan, Division of Pulmonary Diseases, Ospedale L. Sacco, ASST Fatebenefratelli-Sacco, Milan, Italy; 6Novartis Farma S.p.A, Milan, ItalyCorrespondence: Giorgio Walter Canonica Tel +39 0282247752Email giorgio_walter.canonica@hunimed.euIntroduction: Inadequately controlled severe asthma patients require additional therapy accounting for significant clinical and economic burden. Our analysis aims to determine the cost-effectiveness of omalizumab in the management of severe allergic asthma in Italy based on observational data from the PROXIMA study.Methods: Observational data on efficacy, healthcare resource utilization and changes in quality of life at 12 months after the initiation of omalizumab were examined to estimate the cost-effectiveness compared to pre-omalizumab period and results were expressed with Incremental Cost-Effectiveness Ratio (ICER). The cost–utility analysis estimated the cost per quality-adjusted life-year (QALY) gained. Direct health costs were assessed from the perspective of the Italian National Health Service (NHS).Results: Omalizumab reduced the incidence of exacerbations, number of hospitalizations, physician visits, and improved quality of life after 12 months of treatment. Omalizumab had a greater effectiveness than pre-omalizumab treatment involving 0.132 QALYs gained and led to a € 3729 per patient reduction in direct healthcare costs, excluding the add-on treatment cost. Nevertheless, the addition of omalizumab cost led to € 7478 increase in total direct costs with respect to pre-omalizumab period. Based on difference in total direct cost and difference in QALY between post and pre-omalizumab period, the ICER was € 56,847. According to sensitivity analysis, omalizumab provided a cost-effective use of NHS resources, already at 20% discounted price.Conclusion: This study offers a real-world evidence of omalizumab effectiveness in Italy. Despite the high acquisition cost of the innovative drug, omalizumab is a sustainable treatment option for patients with uncontrolled severe allergic asthma.Keywords: severe allergic asthma, healthcare costs, effectiveness, cost-utility, omalizumab, PROXIMA study

Giorgio L Colombo,1,2 Sergio Di Matteo,2 Chiara Martinotti,2 Steffen M Jugl,3 Praveen Gunda,4 Mariantonietta Naclerio,5 Giacomo M Bruno2 1Department of Drug Science, Pavia University, Pavia, Italy; 2S.A.V.E. S.r.l. Studi Analisi Valutazioni Economiche Health Economics & Outcomes Research - research center, Milan, Italy; 3Novartis Pharma AG, Basel, Switzerland; 4Novartis Healthcare Private Limited, Hyderabad, India; 5Novartis Farma S.p.A, Origgio, Varese, Italy Objective: Secukinumab, a fully human monoclonal IgG1 antibody that selectively neutralizes the proinflammatory cytokine IL-17A, has been approved in Europe in 2015 for the treatment of adult patients with moderate-to-severe plaque psoriasis, psoriatic arthritis (PsA), and ankylosing spondylitis (AS). This analysis assessed the budget impact of introduction of secukinumab to the Italian market for all three indications from the perspective of the Italian National Health Service. Materials and methods: A cross-indication budget impact model was developed and included biologic-treated adult patients diagnosed with psoriasis, PsA, and AS. The analyses were conducted over a 3-year time horizon and included direct costs (drug therapy costs, administration costs, diseases-related costs, and adverse events costs). Model input parameters (epidemiology, market share projections, resource use, and costs) were obtained from the published literature and other Italian sources. The robustness of the results was tested via one-way sensitivity analyses: secukinumab cost, secukinumab market share, intravenous administration costs, and adverse events costs were varied by ±10%. Results: The total patient population for secukinumab over the 3-year timeframe was projected to be 6,648 in the first year, increasing to 12,001 in the third year, for all three indications combined (psoriasis, PsA, and AS). Compared to a scenario without secukinumab in the market, the introduction of secukinumab in the market for the treatment of psoriasis, PsA, and AS showed a cumulative 3-year incremental budget impact of -5%, corresponding to savings of €66.1 million and per patient savings of about €1,855. The majority of the cost savings came from the adoption of secukinumab in AS (58%), followed by PsA (29%) and psoriasis (13%). Sensitivity analyses confirmed the robustness of the results. Conclusion: Results from this cross-indication budget impact model show that secukinumab is a cost-saving option for the treatment of PsA, AS, and psoriasis patients in Italy. Keywords: budget impact, psoriasis, psoriatic arthritis, ankylosing spondylitis, Italy, secukinumab

Enrico Torre,1 Giacomo Matteo Bruno,2 Sergio Di Matteo,2 Chiara Martinotti,2 Martina Oselin,2 Maria Chiara Valentino,2 Alessio Parodi,3 Luigi Carlo Bottaro,4 Giorgio Lorenzo Colombo5 1Endocrinology, Diabetology and Metabolic Diseases Unit, ASL3, Genoa, Italy; 2S.A.V.E. Studi Analisi Valutazioni Economiche S.r.l., Health Economics & Outcomes Research, Milan, Italy; 3General Direction International Evangelic Hospital, Genoa, Italy; 4General Direction, ASL3, Genoa, Italy; 5Department of Drug Sciences, University of Pavia, Pavia, Italy Background: Diabetes represents a relevant public health problem worldwide due to its increasing prevalence and socioeconomic burden. There is no doubt that tight glycemic control reduces the development of diabetic complications such as the long-term costs related to the disease. The aim of our model was to calculate total direct costs associated with the two treatments considered in DUAL VII study, and hence evaluate the potential economic benefits for the National Health System (NHS) deriving from the use of insulin degludec plus liraglutide (IDegLira) in a once-daily fixed combination. Materials and methods: We applied the cost-minimization technique adopting the NHS point of view to the DUAL VII trial outcomes. In the model, developed in Microsoft Excel®, we calculated and compared annual costs per patient of the two therapeutic options for type 2 diabetes (T2D) patients not achieving glycemic control on basal insulin and metformin described in the trial, including costs of therapy management and side effects, both negative and positive. Annual treatment costs were calculated based on IDegLira and basal bolus end-of-trial doses resulting in a 1:2 ratio (40.4 U vs 84.1 U). Therefore, maintaining the IDegLira/basal bolus at 1:2 dose ratio, we calculated the correlation between the dose reduction and costs compared to DUAL VII doses base case scenario. Results: Total treatment costs were obtained by adding annual cost of drug, needles, glycemic self-monitoring, hypoglycemic events, and effect on consumption of other drugs. Total annual costs of IDegLira combination resulted in €434 higher than basal bolus in DUAL VII base case (40.4 U); the two treatments reported equal costs at 34% dose reduction (26.7 U), while below this value IDegLira treatment became less expensive, with about €215 gain at 50% dose reduction (20.2 U). It is also important to notice that above the break-even point, until an IDegLira dose of 30 U, the cost difference is negligible in view of the clinical benefit provided by the fixed combination highlighted in DUAL VII trial. Conclusion: Adding the significant clinical findings derived from DUAL VII trial to our economic evaluation, IDegLira seems to offer an important alternative to basal-bolus therapy. Keywords: diabetes, cost minimization, IDegLira, basal-bolus therapy

Giorgio L Colombo,1,2 Sergio Di Matteo,2 Chiara Martinotti,2 Martina Oselin,2 Giacomo M Bruno,2 Gianfranco M Beghi3 1Department of Drug Sciences, University of Pavia, Pavia, Italy; 2S.A.V.E. Studi Analisi Valutazioni Economiche S.r.l., Health Economics & Outcomes Research, Milan, Italy; 3Unit of Pulmonary Rehabilitation, Hospital of Casorate Primo, Pavia, Italy Background: Anas barbariae hepatis et cordis extractum 200K (Oscillococcinum®) is used to treat and prevent seasonal colds and airway inflammatory affections, improve symptom control, and reduce the frequency of respiratory tract infection (RTI) episodes. The objective of this controlled observational study is to investigate, from the Italian National Health Service (NHS) point of view, the role of Anas barbariae hepatis et cordis extractum 200K in preventing RTIs and estimate the annual average cost per patient due to visits and medicines in a real-world setting, investigating whether this method of treatment can bring savings for the NHS.Methods: Data from a single center from 2002 to 2011 were used. The analysis examined 455 patients who suffered from respiratory diseases. Of the total number of patients, 246 were treated with Anas barbariae hepatis et cordis extractum 200K while 209 were not treated (Control group). All the data concerning RTI episodes, pharmacological treatments, and pneumological visits were extracted from the database.Results: It was found that, regardless of the diagnosis, the frequency of RTI episodes was always lower in patients treated with Anas barbariae hepatis et cordis extractum 200K; the difference between the numbers of events occurring was statistically significant in every class of patients (p

Anna Testa,1 Fabiana Castiglione,1 Olga Maria Nardone,1 Giorgio L Colombo2 1Gastroenterology, University of Naples Federico II, Naples, 2Department of Drug Sciences, University of Pavia, Pavia, Italy Abstract: Medication adherence is an important challenge while treating chronic illnesses, such as ulcerative colitis (UC), that require a long-term management to induce and maintain clinical remission. This review provides an overview of the role that medication adherence plays in the routine management of UC, with a focus on the results of a recent Italian study reporting the perception of patients with UC regarding adherence to treatment. A literature analysis was conducted on topics, such as measurement of adherence in real practice, causes, risk factors and consequences of non-adherence and strategies, to raise patients’ adherence. Most of the data refer to adherence to 5-aminosalicylic acid, and standard of care for the induction and maintenance of remission in UC. The adherence rate to 5-aminosalicylic acid is low in clinical practice, thus resulting in fivefold higher risk of relapse, likely increased risk of colorectal cancer, reduced quality of life and higher health care costs for in- and outpatient settings. There are various causes affecting non-adherence to therapy: forgetfulness, high cost of drugs, lack of understanding of the drug regimen – which are sometimes due to insufficient explanation by the specialist – anxiety created by possible adverse events, lack of confidence in physicians’ judgment and complex dosing regimen. The last aspect negatively influences adherence to medication both in clinical trial settings and in real-world practice. Regarding this feature, mesalamine in once-daily dosage may be preferable to medications with multiple doses per day because the simplification of treatment regimens improves adherence. Keywords: adherence, ulcerative colitis, 5-ASA, mesalamine, once-daily

Anna Poli,1 Sergio Di Matteo,2 Giacomo M Bruno,2 Enrica Fornai,1 Maria Chiara Valentino,2 Giorgio L Colombo2,31Vigilanza e Controllo Infezioni Correlate all'Assistenza, Ospedale Piero Palagi, Azienda Sanitaria di Firenze, Firenze, Italy; 2SAVE Studi – Health Economics and Outcomes Research, Milan, Italy; 3Department of Drug Sciences, University of Pavia, Pavia, ItalyIntroduction: Despite the awareness about the increasing rates of Clostridium difficile infection (CDI) and the economic burden arising from its management (prolonged hospitalization, laboratory tests, visits, surgical treatment, environmental sanitation), few studies are available in Italy on the economic costs directly attributable to the CDI. The Florence health care system has designed a study with the aim of describing the costs attributable to the CDI and defines the incremental economic burden associated with the management of this complication.Methods: We conducted a retrospective study in five hospitals of the Florence health care system. The enrolled population included all patients who were hospitalized during the year 2013 with a diagnosis of CDI. Of the 187 total cases reported in 2013, 69 patients were enrolled, for whom the main cause of hospitalization was directly attributable to CDI.Results: We enrolled 69 patients (19 males and 50 females), with a mean age of 82.16 years (minimum 46 to maximum 98). The total number of hospitalization days observed was 886 (12.8 per patient on average). The data from this study show that the mean total incremental cost for a patient with CDI was €3,270.52 per year. The hospital stay length is the most significant cost parameter, having the largest influence on the overall costs, with an impact of 87% on the total cost. The results confirm the costs for the management of CDI in five hospitals of the Florence health care system are in line with data from the international literature.Conclusion: The economic impact of CDI is most evident in the extension of the duration of hospitalization and emergency recurrences requiring new therapeutic options with the need to develop and implement new diagnostic and therapeutic algorithms in clinical practice.Keywords: cost of illness, burden of disease, pharmacoeconomics, cost analysis

Giorgio Lorenzo Colombo,1 Calogero Cammà,2 Adolfo Francesco Attili,3 Roberto Ganga,4 Giovanni Battista Gaeta,5 Giuseppina Brancaccio,5 Jean Marie Franzini,6 Marco Volpe,6 Giuseppe Turchetti7 1Department of Drug Sciences, University of Pavia, Pavia, Italy; 2Section of Gastroenterology, Di.Bi.M.I.S., University of Palermo, Palermo, Italy; 3Department of Clinical Medicine, University of Rome (La Sapienza) Rome, Italy; 4Clinical Medicine Division, Ospedale Brotzu, Cagliari, Italy; 5Viral Hepatitis Unit, Second University, Naples, Italy; 6Business Integration Partners S.p.A., Milan, Italy; 7Scuola Superiore Sant’Anna, Pisa, Italy Background: Hepatocellular carcinoma (HCC) is a severe health condition associated with high hospitalizations and mortality rates, which also imposes a relevant economic burden.Purpose: The aim of the present survey is to investigate treatment strategies and related costs for HCC in the intermediate and advanced stages of the disease. Patients and methods: The survey was conducted in four Italian centers through structured interviews with physicians. Information regarding the stage of disease, treatments performed, and related health care resource consumption was included in the questionnaire. Direct health care cost per patient associated with the most relevant treatments such as sorafenib, transarterial chemoembolization (TACE), and transarterial radioembolization (TARE) was evaluated.Results: Between 2013 and 2014, 285 patients with HCC were treated in the four participating centers; of these, 80 were in intermediate stage HCC (Barcelona Clinic Liver Cancer Classification [BCLC] B), and 57 were in the advanced stage of the disease (BCLC C). In intermediate stage HCC, the most frequent first-line treatment was TACE (63%) followed by sorafenib (15%), radiofrequency ablation (14%), and TARE (1.3%). In the advanced stage of HCC, the most frequently used first-line therapy was sorafenib (56%), followed by best supportive care (21%), TACE (18%), and TARE (3.5%). The total costs of treatment per patient amounted to €12,214.54 with sorafenib, €13,418.49 with TACE, and €26,106.08 with TARE. Both in the intermediate and in the advanced stage of the disease, variability in treatment patterns among centers was observed.Conclusion: The present analysis raises for the first time the awareness of the overall costs incurred by the Italian National Healthcare System for different treatments used in intermediate and advanced HCC. Further investigations would be important to better understand the effective health care resource usage. Keywords: disease costs, drugs cost, transarterial embolization, sorafenib

Franco Maggiolo,1 Giorgio L Colombo,2,3 Sergio Di Matteo,3 Giacomo M Bruno,3 Noemi Astuti,1 Elisa Di Filippo,1 Giulia Masini,1 Claudia Bernardini1 1Division of Infectious Diseases, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy; 2University of Pavia, Department of Drug Sciences, Pavia, Italy; 3SAVE Studi Analisi Valutazioni Economiche, Milan, Italy Objectives: Costs may play a role in deciding how and when to start highly active antiretroviral therapy (HAART) in a naïve patient. The aim of the present study was to assess the cost- effectiveness of treatment with HAART in a large clinical cohort of naïve adults to determine the potential role of single-tablet regimens in the management of patients with human immunodeficiency virus (HIV). An incremental cost-effectiveness ratio analysis was performed, including a quality-adjusted life year approach. Results: In total, 741 patients (females comprising 25.5%) were retrospectively included. The mean age was 39 years, the mean CD4 cell count was 266 cells/µL, and the mean viral load was 192,821 copies/mL. The most commonly used backbone was tenofovir + emtricitabine (77.6%); zidovudine + lamivudine was used in 10%, lamivudine + abacavir in 3%, and other nucleoside reverse transcriptase inhibitor (NRTI) or NRTI-free regimens in 9.4% of patients. NNRTIs were used in 52.8% of cases, boosted protease inhibitors in 44.1%, and unboosted protease inhibitors and integrase inhibitors in 0.7% and 2.4%, respectively. Starting therapy at CD4 >500 cells/µL and CD4 351–500 cells/µL rather than at 500 cells per µL); in this case, the incremental cost-effectiveness ratio value was €199,130 per quality-adjusted life year gained, a higher value than the one suggested in guidelines. The single-tablet regimen (STR) invariably dominated any other therapeutic approach. Sensitivity analysis was performed, and starting right away with an STR was cost-effective even when compared with therapeutic strategies contemplating STR as simplification. Conclusion: By integrating clinical data with economic variables, our study offers an estimate of the cost-effectiveness of the various first-line treatment strategies for patients infected with HIV and provides significant evidence to be used in future prospective pharmacoeconomic evaluations. Keywords: cost-effectiveness, quality-adjusted life years, highly active antiretroviral therapy, single-tablet regimen

Giorgio L Colombo,1,2 Daria Bettoni,3 Sergio Di Matteo,2 Camilla Grumi,3 Cinzia Molon,4 Daniela Spinelli,5 Gaetano Mauro,6 Alessia Tarozzo,4 Giacomo M Bruno2 1Department of Drug Sciences, University of Pavia, Pavia, Italy; 2Studi Analisi Valutazioni Economiche (SAVE), Milan, Italy; 3Hospital Pharmacy, Spedali Civili Brescia, Brescia, Italy; 4Città della Salute e della Scienza di Torino, Presidio Molinette, Turin, Italy; 5Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy; 6Scuola di Specializzazione in Farmacia Ospedaliera, Università La Sapienza, Roma, Italy Background: TachoSil® is a medicated sponge coated with human fibrinogen and human thrombin. It is indicated as a support treatment in adult surgery to improve hemostasis, promote tissue sealing, and support sutures when standard surgical techniques are insufficient. This review systematically analyses the international scientific literature relating to the use of TachoSil in hemostasis and as a surgical sealant, from the point of view of its economic impact. Methods: We carried out a systematic review of the PubMed literature up to November 2013. Based on the selection criteria, papers were grouped according to the following outcomes: reduction of time to hemostasis; decrease in length of hospital stay; and decrease in postoperative complications. Results: Twenty-four scientific papers were screened, 13 (54%) of which were randomized controlled trials and included a total of 2,116 patients, 1,055 of whom were treated with TachoSil. In the clinical studies carried out in patients undergoing hepatic, cardiac, or renal surgery, the time to hemostasis obtained with TachoSil was lower (1–4 minutes) than the time measured with other techniques and hemostatic drugs, with statistically significant differences. Moreover, in 13 of 15 studies, TachoSil showed a statistically significant reduction in postoperative complications in comparison with the standard surgical procedure. The range of the observed decrease in the length of hospital stay for TachoSil patients was 2.01–3.58 days versus standard techniques, with a statistically significant difference in favor of TachoSil in eight of 15 studies. Conclusion: This analysis shows that TachoSil has a role as a supportive treatment in surgery to improve hemostasis and promote tissue sealing when standard techniques are insufficient, with a consequent decrease in postoperative complications and hospital costs. Keywords: TachoSil®, systematic review, economic evaluation, cost analysis, outcomes research

Enrico Papaleo,1 Carlo Alviggi,2 Giorgio Lorenzo Colombo,3,4 Claudio Pisanelli,5,6 Claudio Ripellino,7 Salvatore Longobardi,8 Pier Luigi Canonico91Centro Scienze della Natalità, Gynecological-Obstetrics Department, San Raffaele Hospital, Vita-Salute San Raffaele, Milan, Italy; 2Department of Neuroscience, Reproductive Sciences and Odontostomatology, University “Federico II” of Naples, Naples, Italy; 3Department of Drug Sciences, University of Pavia, Pavia, Italy; 4SAVE Studi Analisi Valutazioni Economiche, Milan, Italy; 5ACO San Filippo Neri, Rome, Italy; 6Società Italiana Di Farmacia Ospedaliera, Milan, Italy; 7CSD Medical Research Srl, Milan, Italy; 8Medical Department, Merck Serono SpA, Rome, Italy; 9Department of Pharmaceutical Sciences, University of Piemonte Orientale, Novara, Italy Background: Hypogonadotropic hypogonadal women are characterized by ovarian functionality deficiency, caused by low concentrations of follicle-stimulating hormone (FSH) and luteinizing hormone (LH). To recover reproduction functionality, recommended therapies for ovarian induction involve injections of FSH and LH medications. Objective: Since important differences exist between recombinant and urinary gonadotropin therapies in terms of efficacy and cost, the objective of this study was to develop a cost-effectiveness model to compare recombinant FSH (rFSH) + recombinant LH (rLH) and highly purified human menopausal gonadotropin (HP-HMG). Methods: A Markov model was developed, considering three cycles of therapy; probability of pregnancy and miscarriage were considered, and the efficacy was evaluated in terms of pregnancy occurrence. The perspective of the model was that of the Italian Health Service, so only direct cost (drugs, specialist visits, patient examinations, and hospitalizations) were included. Results: rFSH + rLH is associated with a higher total cost (€3,453.50) and higher efficacy (0.87) compared with HP-HMG (€2,719.70 and 0.50). rFSH + rLH generated an incremental cost effectiveness ratio equal to €2,007.30 compared to HP-HMG; the average cost per pregnancy is estimated to be €3,990.00 for recombinant strategy and €5,439.80 for urinary strategy. Results of probabilistic sensitivity analysis were consistent with the abovementioned findings. Conclusion: Despite the higher acquisition cost in comparison to HP-HMG, rFSH + rLH resulted in a higher pregnancy rate, which makes it the recommended choice when considering cost-effectiveness of LH in supporting FSH-induced follicular gonadotropins in hypogonadotropic hypogonadal women. Keywords: HP-HMG, hypogonadotropic hypogonadism, gonadotropin

Giorgio L Colombo,1,2 Antonella Castagna,3 Sergio Di Matteo,2 Laura Galli,3 Giacomo Bruno,2 Andrea Poli,3 Stefania Salpietro,3 Alessia Carbone,3 Adriano Lazzarin3,41Department of Drug Sciences, School of Pharmacy, University of Pavia, Italy; 2Studi Analisi Valutazioni Economiche (S.A.V.E.), Milan, 3Infectious Diseases Department, San Raffaele Hospital, Milan, 4Vita-Salute San Raffaele University, Milan, ItalyObjective: In the study reported here, single-tablet regimen (STR) versus (vs) multi-tablet regimen (MTR) strategies were evaluated through a cost analysis in a large cohort of patients starting their first highly active antiretroviral therapy (HAART). Adult human immunodeficiency virus (HIV) 1-naïve patients, followed at the San Raffaele Hospital, Milan, Italy, starting their first-line regimen from June 2008 to April 2012 were included in the analysis.Methods: The most frequently used first-line HAART regimens (>10%) were grouped into two classes: 1) STR of tenofovir disoproxil fumarate (TDF) + emtricitabine (FTC) + efavirenz (EFV) and 2) MTR including TDF + FTC + EFV, TDF + FTC + atazanavir/ritonavir (ATV/r), TDF + FTC + darunavir/ritonavir (DRV/r), and TDF + FTC + lopinavir/ritoavir (LPV/r). Data were analyzed from the point of view of the Lombardy Regional Health Service. HAART, hospitalizations, visits, medical examinations, and other concomitant non-HAART drug costs were evaluated and price variations included. Descriptive statistics were calculated for baseline demographic, clinical, and laboratory characteristics; associations between categorical variables and type of antiretroviral strategy (STR vs MTR) were examined using chi-square or Fisher's exact tests. At multivariate analysis, the generalized linear model was used to identify the predictive factors of the overall costs of the first-line HAART regimens.Results: A total of 474 naïve patients (90% male, mean age 42.2 years, mean baseline HIV-RNA 4.50 log10 copies/mL, and cluster of differentiation 4 [CD4+] count of 310 cells/µL, with a mean follow-up of 28 months) were included. Patients starting an STR treatment were less frequently antibody-hepatitis C virus positive (4% vs 11%, P=0.040), and had higher mean CD4+ values (351 vs 297 cells/µL, P=0.004) than MTR patients. The mean annual cost per patient in the STR group was €9,213.00 (range: €6,574.71-€33,570.00) and €14,277.00 (range: €5,908.89-€82,310.30) among MTR patients. At multivariate analysis, after adjustment for age, sex, antibody-hepatitis C virus status, HIV risk factors, baseline CD4+, and HIV-RNA, the cost analysis was significantly lower among patients starting an STR treatment than those starting an MTR (adjusted mean: €12,096.00 vs €16,106.00, P=0.0001).Conclusion: STR was associated with a lower annual cost per patient than MTR, thus can be considered a cost-saving strategy in the treatment of HIV patients. This analysis is an important tool for policy makers and health care professionals to make short- and long-term cost projections and thus assess the impact of these on available budgets.Keywords: HIV, HAART, single tablet regimen, pharmacoeconomics, multi-tablet regimen

Giorgio L Colombo,1,2 Ivo A Bergamo Andreis,3 Sergio Di Matteo,2 Giacomo M Bruno,2 Claudio Mondellini31Department of Drug Sciences, University of Pavia, Italy; 2Studi Analisi Valutazioni Economiche (S.A.V.E.), Milan, Italy; 3Department of Radiology, City Hospital, Legnano, ItalyObjective: The utilization of diagnostic imaging has substantially increased over the past decade in Europe and North America and continues to grow worldwide. The purpose of this study was to develop an economic evaluation of a syringeless power injector (PI) versus a dual-syringe PI for contrast enhanced computed tomography (CECT) in a hospital setting.Materials and methods: Patients (n=2379) were enrolled at the Legnano Hospital between November 2012 and January 2013. They had been referred to the hospital for a CECT analysis and were randomized into two groups. The first group was examined with a 256-MDCT (MultiDetector Computed Tomography) scanner using a syringeless power injector, while the other group was examined with a 64-MDCT scanner using a dual-syringe. Data on the operators' time required in the patient analysis steps as well as on the quantity of consumable materials used were collected. The radiologic technologists' satisfaction with the use of the PIs was rated on a 10-point scale. A budget impact analysis and sensitivity analysis were performed under the base-case scenario.Results: A total of 1,040 patients were examined using the syringeless system, and 1,339 with the dual-syringe system; the CECT examination quality was comparable for both PI systems. Equipment preparation time and releasing time per examination for syringeless PIs versus dual-syringe PIs were 100±30 versus 180±30 seconds and 90±30 and 140±20 seconds, respectively. On average, 10±3 mL of contrast media (CM) wastage per examination was observed with the dual-syringe PI and 0±1 mL with the syringeless PI. Technologists had higher satisfaction with the syringeless PI than with the dual-syringe system (8.8 versus 8.0). The syringeless PI allows a saving of about €6.18 per patient, both due to the lower cost of the devices and to the better performance of the syringeless system. The univariate sensitivity analysis carried out on the base-case results within the standard deviation range confirmed the saving generated by using the syringeless device, with saving values between €5.40 and €6.20 per patient.Conclusion: The syringeless PI was found to be more user-friendly and efficient, minimizing contrast wastage and providing similar contrast enhancement quality compared to the dual-syringe injector, with comparable CECT examination quality.Keywords: dual-syringe power injector, syringeless power injector, economic evaluation, cost analysis, computed tomography, CT

Giorgio L Colombo,1,2 Sergio Di Matteo,2 Andrea Antinori,3 Massimo Medaglia,4 Silvia Murachelli,3 Giuliano Rizzardini51Department of Drug Sciences, University of Pavia, Pavia, Italy; 2SAVE – Studi Analisi Valutazioni Economiche, Milan, Italy; 3National Institute for Infectious Diseases L Spallanzani, IRCCS, Rome, Italy; 4Pharmaceutical Department, L. Sacco Hospital, Milan, Italy; 5First Division of Infectious Disease, L. Sacco Hospital, Milan, Italy Introduction: Highly active antiretroviral therapy (HAART) has allowed many HIV-infected patients to enjoy longer survival and a better quality of life. We performed an economic analysis to estimate the cost-effectiveness of HAART regimens in Italy for managing HIV-naïve infected patients with a viral load below 100,000 copies/mL.Patients and methods: The population considered in the model consisted of adult subjects with an HIV viral load below 100,000 copies/mL who received antiretroviral HAART treatment for the first time, according to the Italian National Guidelines with recommendation grade A1. The incremental cost-effectiveness analysis of quality-adjusted life years (QALYs) was carried out by means of a Markov model. Both the outcomes (QALYs) and the costs were discounted by 3.5%. The time horizon adopted in the model was 10 years. The point of view of the analysis was that of the Italian national health service.Results: The tenofovir (TDF)/emtricitabine (FTC)/rilpivirine (RPV) single-tablet regimen (STR) (€7,417.00) revealed the lowest mean treatment cost. TDF/FTC + raltegravir (RAL) showed a better quality of life (0.906 QALY/year), followed by TDF/FTC/RPV (STR; 0.900 QALY/year), TDF/FTC + RPV (multipill regimen) (0.889 QALY/year), and TDF/FTC + atazanavir (ATV/r) (0.886 QALY/year). TDF/FTC/RPV (STR) appeared to be the most cost-effective therapeutic choice (€13,655.00), followed by TDF/FTC + RPV (multipill regimen) (€15,803.00), and TDF/FTC + efavirenz (EFV) (€16,181.00). The sensitivity analysis on the main variables confirmed the validity of the base case scenario.Conclusion: STR (TDF/FTC/RPV) is the most cost-effective treatment strategy compared with the other therapeutic regimens recommended by the Italian guidelines for the treatment of naïve patients with a viral load

Giorgio L Colombo,1,2 Sergio Di Matteo,2 Marta Vinci,3 Claudia Gatti,4 Maria Paola Pascali,5 Mario De Gennaro,6 Elena Macrellino,7 Giovanni Mosiello,5 Tiziana Redaelli,7 Francesca Schioppa,7 Cristina Dieci8 1University of Pavia, Department of Drug Sciences, School of Pharmacy, Pavia, Italy; 2S.A.V.E. Studi Analisi Valutazioni Economiche, Milan, Italy; 3Associazione Walter Vinci Onlus, Milan, Italy; 4Centro Spina Bifida, Azienda Ospedaliera di Parma, Parma, Italy; 5Centro Spina Bifida, Ospedale Pediatrico Bambino Gesù, Rome, Italy; 6Ospedale Pediatrico Bambino Gesù, O.C. di Urodinamica, Rome, Italy; 7Centro Spina Bifida, Ospedale Niguarda Milan, Italy; 8ASBI Associazione Spina Bifida Italia, Piacenza, Italy Introduction: Spina bifida (SB) is a congenital malformation of the spinal cord, nerves, and adjacent covering structures, with different levels of severity and functional disability. The economic cost of spina bifida and its prevention using folic acid have never been estimated in Italy. This study was conducted to define the cost of illness of SB in Italy. Methods: A retrospective multicenter observational study on the social cost of patients with SB was carried out in three SB centers in Italy. Cost data were collected relating to the 12 months preceding the enrollment time (T0), and subsequently 3 months after the T0 time (±20 days) through a case report form designed to collect the relevant information on the costs incurred during the period considered. The data for all patients were analyzed through multivariate analysis on the main parameters. Results: We enrolled 128 patients equally divided between males and females, with a mean age of 13 years (minimum, 0; maximum, 29). Diagnosis was mostly postnatal, with 64 cases diagnosed at birth and 33 cases diagnosed subsequently. The lesion severity levels, as defined in the inclusion criteria, were walking (52 patients); walking with simple orthoses (33 patients); walking with complex orthoses (16 patients); and nonwalking, (25 patients). The anatomic type identified is open SB in most cases (84 patients), followed by closed SB (37 patients) and SB occulta (3 patients). The most significant cost per year was for assistive devices, for a total of 4307.00 €, followed by hospitalization (907.00 €), examinations (592.00 €), and drug therapy (328.00 €). Cost breakdown by age range shows that the highest costs are incurred in the 0–4 age range. The highest cost was for cases of open SB (12,103.00 €). The cost/degree of severity ratio showed that the highest cost was for nonwalking patients (14,323.00 €), followed by patients walking with complex orthoses (13,799.00 €). Conclusion: The data from this study show that the mean total cost for a patient with SB was 11,351.00 € per year. Based on data provided by the Italian Institute of Health, we can estimate a total annual social cost of about 60 million Euros per year for SB in Italy. Cost of illness was correlated with age and degree of severity of SB. Keywords: spina bifida, cost of illness, pharmacoeconomics, cost analysis

Giorgio L Colombo,1,2 Sergio Di Matteo,2 Franco Maggiolo31University of Pavia, Department of Drug Sciences, School of Pharmacy, Pavia, Italy, 2Studi Analisi Valutazioni Economiche, Milan, Italy, 3Division of Infectious Diseases, Ospedali Riuniti, Bergamo, ItalyBackground: The aim of this study was to assess the economic value of a reduced number of pills in patients infected with the immunodeficiency virus (HIV) and on highly active antiretroviral therapy by a cost-effectiveness model.Methods: An incremental cost-effectiveness analysis of efavirenz, tenofovir, and emtricitabine (TDF-FTC-EFV) as a single-tablet regimen versus a multipill regimen, with reference to untreated HIV-infected patients, was carried out from the perspective of the Italian National Health Service. The comparisons were performed with the help of a Markov decision model over a 10-year time horizon. Based on the ADONE (ADherence to ONE pill) study, it was then possible to identify the utility score increment in patients switching from a multipill regimen of TDF-FTC + EFV therapy to a single-tablet regimen.Results: The single-tablet regimen (0.755 quality-adjusted life-years [QALYs]/year) resulted in better patient quality of life, with a higher number of QALYs than for the TDF-FTC + EFV multipill regimen (0.716 QALYs/year). The single-tablet regimen was the most cost-effective treatment strategy, with an incremental cost-effectiveness ratio of €22,017.00 versus €26,558.00 for the multipill regimen. A 24% decrease in cost of the multipill regimen determined equivalence with the single-tablet regimen in terms of the incremental cost-effectiveness ratio. Univariate sensitivity and probabilistic analysis carried out on the main variables did not highlight significant variations with respect to the base case scenario.Conclusion: The single-tablet regimen resulted in better adherence, and therefore better quality of life as perceived by patients, corresponding to a €4541.00 lower cost-effectiveness ratio per QALY versus the multipill regimen, with a 17% lower cost in favor of the single-tablet regimen. The value determined could be used to identify a maximum potential "premium price" of 29% to be assigned to therapeutic regimens proposing a single-tablet regimen for HIV-infected patients.Keywords: tenofovir, emtricitabine, efavirenz, single-tablet regimen, highly active antiretroviral therapy, quality of life, pharmacoeconomics, adherence

Isabella Ruggeri,1 Donatello Bragato,2 Giorgio L Colombo,3,4 Emanuela Valla,3 Sergio Di Matteo41Servizio Governo Area Farmaceutica, Azienda Sanitaria Locale, Milano, Binasco, 2Data Solution Provider, Milan, 3University of Pavia, Department of Drug Sciences, School of Pharmacy, 4Studi Analisi Valutazioni Economiche, MilanBackground: Bronchial asthma is a chronic airways disease and is considered to be one of the major health problems in the Western world. During the last decade, a significant increase in the use of β2-agonists in combination with inhaled corticosteroids has been observed. The aim of this study was to assess the appropriateness of expenditure on these agents in an asthmatic population treated in a real practice setting.Methods: This study used data for a resident population of 635,906 citizens in the integrated patient database (Banca Dati Assistito) of a local health care unit (Milano 2 Azienda Sanitaria Locale) in the Lombardy region over 3 years (2007–2009). The sample included 3787–4808 patients selected from all citizens aged ≥ 18 years entitled to social security benefits, having a prescription for a corticosteroid + β2-agonist combination, and an ATC code corresponding to R03AK, divided into three groups, ie, pressurized (spray) drugs, inhaled powders, and extrafine formulations. Patients with chronic obstructive lung disease were excluded. Indicators of appropriateness were 1–3 packs per year (underdosed, inappropriate), 4–12 packs per year (presumably appropriate), and ≥13 packs per year (overtreatment, inappropriate).Results: The corticosteroid + β2-agonist combination per treated asthmatic patient increased from 37% in 2007 to 45% in 2009 for the total of prescribed antiasthma drugs, and 28%–32% of patients used the drugs in an appropriate manner (4–12 packs per years). The cost of inappropriately used packs increased combination drug expenditure by about 40%, leading to inefficient use of health care resources. This trend improved during the 3-year observation period. The mean annual cost per patient was higher for powders (€223.95) and sprays (€224.83) than for extrafine formulation (€142.71).Conclusion: Based on this analysis, we suggest implementation of better health care planning and more appropriate prescription practices aimed at optimizing use of health care resources for the treatment of bronchial asthma. The results of our study should be extended to other regional/national reference local health care units, in order to define and compare average standard costs per pathology, and consolidated through the wide sample considered.Keywords: asthma, antiasthma drugs, general medicine, appropriateness, pharmacoeconomics, health economics

Giuliano Rizzardini,1 Paolo Bonfanti,2 Laura Carenzi,1 Massimo Coen,1 Giovanna Orlando,1 Sergio Di Matteo,3 Giorgio L Colombo3,411st Infectious Diseases Department, “L. Sacco” Hospital, Milan, Italy; 2Infectious Diseases Department, A Manzoni Hospital, Lecco, Italy; 3S.A.V.E. Studi Analisi Valutazioni Economiche, Milan, Italy; 4University of Pavia, Department of Drug Sciences, School of Pharmacy, ItalyIntroduction: We carried out an economic analysis to assess the cost-effectiveness of highly active antiretroviral therapy (HAART) regimens in Italy for the management of human immunodeficiency virus (HIV)-infected patients according to clinical practice in the Infectious Diseases Department of “L. Sacco” Hospital, Milan, Italy.Patients and methods: The incremental cost-effectiveness analysis was completed by means of a Markov model. Through a decision-analytic approach, this enabled us to compare the studied antiretroviral regimens. The model considered a population of adult HIV subjects who received HAART therapy for the first time according to clinical practice in the Infectious Diseases Department of “L. Sacco” Hospital, Milan. Data were investigated from the standpoint of the Lombardy Regional Health Service. We considered the following outcome measures: quality-adjusted life-years (QALYs), and direct health costs calculated for the years 2008 and 2009. The time horizon adopted in the model was 2 years.Results: The model revealed that, in terms of cost per gained QALY, the tenofovir disoproxil fumarate + emtricitabine + efavirenz (TDF+FTC+EFV) once-a-day treatment strategy seems to be the most cost-effective therapeutic choice (€34,965); the incremental cost-effectiveness ratio (ICER) values for the remaining strategies ranged from €53,000 to around €62,000 per QALY. The validity of the base case scenario was then confirmed by means of a sensitivity analysis on the main variables.Conclusion: The TDF+FTC+EFV treatment strategy (TDF/FTC+EFV fixed-dose combination then switched to single-tablet regimen [STR]) in this setting is the most cost-effective treatment strategy compared with the other therapeutic regimens. The ICER value for the TDF+FTC+EFV once-a-day then switched to STR treatment was lower than the internationally generally accepted threshold value of €50,000. The developed model is a tool for policy makers and health care professionals for creating short- and long-term cost projections, with the aim of assessing their impact on the available budgets for HIV patients.Keywords: AIDS, HIV, HAART antiretroviral therapy regimens, single-tablet regimen (STR), Markov model, cost-effectiveness, quality-adjusted life-years, QALYs

Giorgio L Colombo1,2 Sergio Di Matteo,2 Giacomo Bruno,2 Giampiero Girolomoni,3 Gino Antonio Vena41University of Pavia, Department of Drug Sciences, School of Pharmacy, Pavia, Italy; 2S.A.V.E. Studi Analisi Valutazioni Economiche, Milan, Italy; 3Sections of Dermatology and Venereology, Department of Medicine, University of Verona, Verona, Italy; 4Department of Biomedical Sciences and Human Oncology, Unit of Dermatology and Venereology University of Bari, Bari, ItalyBackground: Psoriasis is a chronic inflammatory skin disease with a major impact on the quality of life of affected individuals. Topical therapy has an important role in the treatment of psoriasis. Poor treatment outcomes from topical therapy regimens likely result from poor adherence and ineffective use of medication.Methods: A cost-minimization analysis was performed with the purpose of assessing the use of a gel containing calcipotriol and betamethasone dipropionate (Dovobet® gel) versus the ointment formulation (Dovobet ointment) in the treatment of psoriasis. The analysis was carried out using a Markov model with a one-year time horizon in a hypothetical cohort of patients with a Psoriasis Area and Severity Index score < 10. The model simulates different therapy adherence scenarios for the two different formulations.Results: The Dovobet gel strategy allows a 5% reduction in the number of patients who could potentially be treated with more expensive therapies (biologics and conventional systemic drugs) in comparison with the Dovobet ointment strategy, with a consequent impact on costs for the National Healthcare Service. The total annual cost of Dovobet gel is about €407.00 per patient, ie, 19% less that the total cost of about €500.00 of the Dovobet ointment strategy. The base case results were then examined by sensitivity analysis and budget impact analysis to correlate the various scenarios of Dovobet gel use with cost savings to the National Healthcare Service.Conclusion: The Dovobet gel strategy seems more acceptable to patients, shows better overall adherence, and appears to be favorable from the pharmacoeconomic point of view than the ointment formulation for treatment of patients with mild-to-moderate psoriasis.Keywords: pharmacoeconomics, cost-minimization, cost-consequences, psoriasis, calcipotriol and betamethasone dipropionate, patient adherence

Giorgio L Colombo,1,2 Elisa Rossi,4 Marisa De Rosa,4 Danilo Benedetto,3 Antonio V Gaddi31School of Pharmacy, Department of Drug Sciences, University of Pavia, Pavia, 2S.A.V.E. Studi Analisi Valutazioni Economiche, Milan, 3CINECA – Bologna; 4Centro Aterosclerosi GC Descovich, Dipartimento di Medicina Interna e dell'Invecchiamento, University of Bologna, Bologna, ItalyBackground: Type 2 diabetes has become a disease with a high economic and social impact. The ARNO Observatory is a clinical data warehouse consisting of a network of local health care units (ASL) scattered throughout the Italian territory which collects data on health care consumption for about 10.5 million people. The purpose of this study was to evaluate the use of antidiabetic drugs with particular reference to type of treatment. The analyses were carried out on a sample of 169,375 patients treated with oral blood glucose-lowering drugs in 2008 from a total population of 4,040,624 health care beneficiaries at 12 local health care units in the ARNO Observatory.Methods: Patients were considered “on treatment with oral blood glucose-lowering drugs” if they had received at least one prescription of an antidiabetic drug (Anatomical Therapeutic Chemical code A10B) during 2008. The patients were divided into three treatment groups, ie, monotherapy, fixed-combination drugs, and dual therapy. The following indicators were assessed: number of patients treated with an oral antidiabetic drug, mean number of hospitalizations, mean number of specialist examinations, and mean expenditure per treated patient. Adherence was assessed using the medication possession ratio indicator (MPR).Results: Patients treated with oral blood glucose-lowering drugs comprised 4.2% of the investigated population, and had an average age of 68.9 years. The mean annual number of hospitalizations was lower in the dual therapy group (298 versus 328 per 1000 patients in the sample), while the average number of specialist examinations was lower in the fixed-combination group (30.1 versus 35.1). Patients on monotherapy showed a better percentage of adherence for glimepiride (70.5%) and pioglitazone (70.4%), whereas the best adherence in the fixed-combination therapy group was recorded for metformin + pioglitazone (75.5%). The average annual cost per diabetic patient was €2388, with differences between the monotherapy (€2321), fixed-combination (€2270), and dual therapy (€2465) groups. Fixed combination therapy involved a lower mean expenditure for insulin, other drugs, and specialist and diagnostic care. Thiazolidinediones (such as pioglitazone) showed the lowest average annual cost per patient among the monotherapies, with a marked decrease in costs for hospitalization, specialist care, and diagnostics.Conclusion: The results of our study should be extended to other regional/national reference local health care units in order to define and compare average standard costs per pathology throughout the wide sample considered in this research work. Appropriate drug prescribing is of critical importance in order to achieve therapeutic objectives and to optimize the use of resources in modern health care systems.Keywords: type 2 diabetes, oral antidiabetic drugs, pharmacoeconomics, health care costs, adherence, medication possession ratio

Viviano Benedini,1 Nicola Caporaso,2 Gino Roberto Corazza,3 Zaccaria Rossi,4 Giovanni Fornaciari,5 Mario Cottone,6 Giorgio Frosini,7 Mauro Caruggi,8 Chiara Ottolini,8 Giorgio L Colombo9,10 On behalf of the COSMO Study Group1Department of Gastroenterology, AO Carlo Poma, Mantova; 2Department of Gastroenterology, University of Naples, Federico II, Naples; 3IRCCS Policlinico San Matteo, Pavia; 4Department of Gastroenterology, Ospedale Regina Apostolorum, Albano Laziale, Rome; 5Department of Gastroenterology, Arcispedale S Maria Nuova, Reggio Emilia; 6Medical Division, Azienda Ospedaliera Cervello, Palermo; 7Department of Gastroenterology, Policlinico Universitario Senese, Siena; 8Hospital S Antonio Abate, Gallarate, Varese, 9University of Pavia; School of Pharmacy, Pavia, Lombardy; 10Studi Analisi Valutazioni Economiche (SAVE), Milan, ItalyBackground: This was a prospective observational study designed to evaluate direct and indirect costs and quality of life for patients with Crohn’s disease in Italy from the perspectives of the National Health System and of society.Methods: A total of 162 male and female subjects aged 18–70 years with Crohn’s disease in the active phase and a Crohn’s Disease Activity Index score ≥150 were included in the study. Subjects were recruited from 25 Italian centers on a consecutive basis. The study consisted of four visits undertaken every 6 months with a follow-up period of 18 months. The study started on September 1, 2006 and was completed on April 12, 2010. Multivariate analyses were carried out on demographic characteristics, treatment costs based on the prescribed daily dose, resource use and other cost parameters, and changes in quality of life using the EQ5D questionnaire.Results: Cost of illness per subject with Crohn’s disease in Italy was estimated to be €15,521 per year, with direct costs representing 76% of total costs. Nonhealth care costs and loss of productivity accounted for 24% of total costs. Societal costs during the first months of enrolment were higher compared with costs in the final months of the study. Quality of life measured by the EQ-5D was 0.558 initially and then increased to 0.739, with a mean value of 0.677 during the enrolment period. The cost of illness was not correlated with age or gender.Conclusion: The cost of illness was correlated with quality of life; Crohn’s disease had a negative impact on subjects’ quality of life, and higher costs corresponded to a lower quality of life as measured with the EQ5D. Drug treatment may improve quality of life and reduce hospitalization costs. Our results appear to be in line with the results of other international cost-of-illness studies.Keywords: Crohn’s disease, quality of life, EuroQol, EQ5D, cost-of-illness, cost analysis, economic evaluation

Giorgio L Colombo,1,2 Sergio Di Matteo,2 Giacomo Bruno21Department of Drug Sciences, School of Pharmacy, University of Pavia, Pavia, Italy; 2S.A.V.E. – Studi Analisi Valutazioni Economiche, Milan, ItalyObjective: Alcohol dependence is a common condition associated with high direct and indirect health care costs. The purpose of this analysis was to estimate the economic consequences of acamprosate used as adjuvant therapy in the treatment of alcoholism, defining a budget impact analysis (BIA) from the point of view of the Italian National Health Service (NHS).Methods: We developed a model of disease evolution related to alcoholism using data from the PRAMA study. The hypothetical population included in the decision model was obtained from data from the Ministry of Health. We compared the following treatment strategies: no treatment, standard care (psychotherapy), sodium oxybate (sodium salt-4-hydroxybutyric acid), and acamprosate. The time horizon of the model was 10 years. The costs were evaluated from the NHS perspective.Results: We simulated the path for 69,348 patients treated at the outpatient clinics of the Addiction Services (SerT), and 38,911 patients discharged from hospital. Patients in the acamprosate group had lower alcohol-related events, with a reduction of the total cost. The BIA shows that the increase in the use of acamprosate was associated with a progressive decrease of total costs, calculated as the sum of the diagnosis-related groups (DRG), rehabilitation, and drug costs. The increasing use of acamprosate instead of standard care and sodium oxybate would generate cost savings up to over €6 million over 10 years of simulation.Conclusion: The estimates in the model are based on hypothetical situations; the assumptions of the model as well as their specific impact on treatment effect estimations and clinical implications should be validated in real life. Public health care authorities would benefit from mathematical models designed to estimate the future burden of alcohol dependence together with the impact of treatment and the potential to reduce the incidence and progression of this condition, and the costs of its complications.Keywords: alcohol dependence, acamprosate, budget impact analysis, economic evaluation

Enrico Aitini1, Anna Rossi1, Patrizia Morselli1, Beatrice Vivorio1, Alessandra Bruschi2, Chiara Bottura2, Giorgio L Colombo31Medical Oncology and Hematology Department, 2Administration Department, Carlo Poma Hospital, Mantova, 3School of Pharmacy, University of Pavia, Milan, ItalyBackground: Colorectal cancer is one of the most frequent and lethal cancers. The aim of this study was to analyze the costs relating to treatment of colorectal cancer between Xelox and Folfox-4 at a regional level according to the clinical experience at an Italian hospital in Lombardy.Methods: A cost analysis was carried out regarding resource consumption by patients suffering from colorectal cancer based on data collected over a 12-month period between 2010 and 2011. The analysis involved 40 patients who attended the Department of Medical Oncology and Hematology at Carlo Poma Hospital to undergo adjuvant therapy for colorectal cancer. A chart was created for each patient containing their medical history, their pharmacological therapy indicating the number and duration of chemotherapy cycles, dose in mg administered for each cycle, number of day hospital visits for each cycle, number of days spent in hospital to position the central vein catheter, type of infusion pump used, any subsequent supportive therapy, and any side effects and outpatient visits connected with side effects.Results: The cost analysis shows the savings involved in using Xelox for a single cycle of treatment, ie, approximately €1414.00 per patient (53% compared with Folfox-4). For each single cycle of treatment, the savings generated by using capecitabine compared with 5-FU can be attributed mostly to the fact that oral administration of chemotherapy requires fewer resources and does not require use of a central vein catheter (approximately 70% of overall cost) which amply compensates for the higher cost of capecitabine compared with 5-FU-LV. Sensibility analysis confirms the results of the base-case scenario.Conclusion: The results of our study indicate that infusion via a central vein catheter represents a significant cost, and that substitution with an oral therapy, even when associated with drugs administered intravenously, represents a consistent saving of hospital resources.Keywords: colorectal cancer, capecitabine, oxaliplatin, 5-fluorouracil, Folfox-4, cost analysis, economic evaluation

Giorgio L Colombo1,2, Vincenzo Colangeli3, Antonio Di Biagio4, Sergio Di Matteo2, Claudio Viscoli4, Pierluigi Viale31School of Pharmacy, University of Pavia, Pavia, Italy; 2SAVE - Studi Analisi Valutazioni Economiche, Milan, Italy; 3Clinica Malattie Infettive, Azienda Ospedaliera Sant'Orsola Malpighi Bologna, Alma Mater Studiorum, University of Bologna, Bologna, Italy; 4Clinica Malattie Infettive dell'Ospedale San Martino di Genova, University of Genova, Genova, ItalyIntroduction: Since the mid-1990s, highly active antiretroviral therapy (HAART) has modified the clinical course of human immunodeficiency virus (HIV) infection, reducing the rate of disease progression, the incidence of opportunistic infections, and mortality. The authors of this paper performed an economic analysis to estimate the cost-effectiveness of the HAART regimens in Italy for managing HIV-infected patients according to national guidelines.Patients and methods: The incremental cost-effectiveness analysis was carried out by means of a Markov model, which through a decision-analytic approach, made it possible to compare the studied antiretroviral regimens. The population considered in the model consisted of adult subjects with HIV who received antiretroviral HAART treatment for the first time. The population considered in the analysis reflects the patients’ characteristics according to one of the regional surveillance systems HIV/AIDS infection report currently operating in Italy. The analysis was carried out from the point of view of the Italian health care system. The considered outcome measures were quality-adjusted life years (QALYs) and direct health costs calculated for the year 2010. Both the outcomes (QALYs) and the costs were discounted by 3.5%. The time horizon adopted in the model was 10 years.Results: The model shows, in terms of cost per gained QALY, single tablet regimen (STR) appeared to be the most cost-effective therapeutic choice (€22,017), followed by tenofovir (TDF) + lamivudine + efavirenz (EFV) (€24,526), and TDF/emtricitabine (FTC) + nevirapine (€26,416), and TDF + FTC + EFV (€26,558); the remaining strategies have an incremental costeffectiveness ratio (ICER) value varying from €28,000 to €41,000 per QALY. The sensitivity analysis on the main variables confirmed the validity of the base case scenario.Conclusion: STR is the most cost-effective treatment strategy, compared with the other therapeutic regimens recommended by the Italian guidelines. All the ICER values of the various regimens considered by the Italian guidelines were lower than the threshold value of €50,000 commonly accepted at the international level. The model developed represents a tool for policy makers and health care professionals to make short- and long-term cost projections and thus evaluate their impact on the available budgets for HIV patients.Keywords: antiretroviral therapy regimens, single tablet regimens, STR, Markov model, quality-adjusted life years, QALYs, HAART

ErratumColombo GL, Caruggi M, Di Matteo, et al. 2008. An economic evaluation of aripiprazole vs olanzapine adapted to the Italian setting using outcomes of metabolic syndrome and risk for diabetes in patients with schizophrenia. Neuropsychiatr Dis Treat, 4: 967–976.Page 972, Results, right column, last paragraph. The second sentence should read:In the simulated cohort of 1000 patients, the values with aripiprazole for 26 weeks showed the avoidance of 34 events of diabetes over 5 years (28 in discounted scenario), resulting in total cost savings of €1,933.24 (€1,472.52 in discounted scenario).Page 973, Table 5:Under Events avoided/1000 schizophrenia patients (5 years): 18 should read 28.Under Cost/metabolic syndrome avoided (5 years): −€2,860.52 should read −€1,852.73.