Hospital resource utilisation from HPV-related diseases in England: a real-world cost analysis.

BACKGROUND AND OBJECTIVE: HPV (human papillomavirus) is the virus most often responsible for sexually transmitted infections. The burden of HPV-related diseases on hospital resources represents a major public health problem. The objective of this study was to quantify the lifetime economic burden of HPV-related diseases based on hospital resources from the perspective of National Health Service (NHS) in England. METHODS: Patients' data were extracted, anonymised and aggregated by NHS digital from Hospital Episode Statistics (HES) database of patients admitted in 2015 and followed for three years. Data on hospitalizations were identified according to the International Classification of Diseases (ICD-10 CM). Health Resource Group (HRG) tariffs and National Reference Costs were used to estimate the hospitalization costs of anal, cervical, genital, oropharyngeal cancers as well as anogenital warts and cervical dysplasia. RESULTS: A total of 19,296 hospitalized patients were included in the estimation model, (39% was male and 61% female. At admission, the average age was 60 and 50 years old, respectively). Life-time costs per patients diagnosed with oropharyngeal cancer were £16,911 (£17,142 for male and £16,334 for female), penile cancer £12,539, vaginal cancer £12,676, anal cancer £13.773 (£12,590 for male, £14,525 for female). Cervical cancer accounted for £12,721, whereas cervical dysplasia for £3932. Resource used for hospitalized patients with anogenital warts was equal to £872 (£884 and £856 for men and women, respectively). On average, outpatient accounted for 39% of the total lifetime costs. CONCLUSION: The results of this study highlight that a substantial amount of resources is utilized for the treatment of HPV-related diseases at hospital level in England. These measures have the potential to inform policy decisions to ensure an optimal use of the NHS resources.

Human papillomavirus in Italy: retrospective cohort analysis and preliminary vaccination effect from real-world data.

INTRODUCTION: The objective of this study was to estimate the lifetime risk of hospitalization associated with all major human papillomavirus (HPV)-related diseases in Italy. Moreover, a preliminary vaccination effect was also performed. METHODS: A retrospective, nonrandomized, observational study was developed based on patients hospitalized between 2006 and 2018 in Italy. All hospitalizations were identified through administrative archives, according to the International Classification of Diseases (ICD-9 CM). Information related to the hospital discharges of all accredited public and private hospitals, both for ordinary and day care regimes, was taken into account. We included hospitalizations related to resident patients presenting one of the ICD-9-CM codes as primary or secondary diagnosis: genital warts (GW); 'cervical intraepithelial neoplasia (CIN)' (067.32-067.33); 'condyloma acuminatum' (078.11); 'anal cancers' (AC) (154.2-154.8); oropharyngeal cancers (OC): 'oropharyngeal cancer'(146.0-146.9) and 'head, face and neck cancers' (171.0); genital cancers (GC): 'penis cancer' (187.1-187.9) and 'cervical cancer' (180.0-180.9). Data were stratified by birth year and divided into two groups: (a) cohort born before 1996 (not vaccinable) and (b) cohort born after 1997 (vaccinable-first cohort that could be vaccinated at the beginning of immunization schedule in girls since 2008 in Italy). Disease-specific hospitalization risks for both groups were estimated by sex, year and age. RESULTS: Epidemiological data demonstrate that the peak hospitalization risk occurred at 24-26 years of age for GW (both male and female); 33-41 and 47-54 years for AC males and females, respectively; 53-59 and 52-58 years for OC males and females, respectively; and 54-60 and 39-46 years for GC males and females, respectively. Focusing on GW and GC, vaccinable females demonstrate a significant reduction in hospitalization risks (- 54% on average) compared to nonvaccinable females until 21 years of age (maximum follow-up available for girls born after 1997). Comparing the same birth cohort of males, no differences in hospitalization risk were found. CONCLUSIONS: These results support the importance of primary prevention strategies in Italy and suggest that increased VCRs and time of observation (genital cancers for which vaccination is highly effective, have a latency of some decades) will provide useful information for decision-makers.

Economic burden of HPV9-related diseases: a real-world cost analysis from Italy.

INTRODUCTION: The objectives of this study were to estimate the economic burden of HPV in Italy, accounting for total direct medical costs associated with nine major HPV-related diseases, and to provide a measure of the burden attributable to HPV 6, 11, 16, 18, 31, 33, 45, 52, 58 infections. METHODS: A cost-of-illness incidence-based model was developed to estimate the incidences and costs of invasive cervical cancer, cervical dysplasia, cancer of the vulva, vagina, anus, penis, oropharyngeal, anogenital warts, and recurrent respiratory papillomatosis (RRP) in the context of the Italian National Health System (NHS). We used data from hospital discharge records (HDRs) of an Italian region and conducted a systematic literature review to estimate the lifetime cost per case, the number of incident cases, the prevalence of HPV9 types. Costs of therapeutic options not included in the diagnosis-related group (DRG) tariffs were estimated through a scenario analysis. RESULTS: In 2018, the total annual direct costs were €542.7 million, with a range of €346.7-€782.0 million. These costs could increase considering innovative therapies for cancer treatment (range €16.2-€37.5 million). The fraction attributable to the HPV9 genotypes without innovative cancers treatment was €329.5 million, accounting for 61% of the total annual burden of HPV-related diseases in Italy. Of this amount, €135.9 million (41%) was related to men, accounting for 64% of the costs associated with non-cervical conditions. CONCLUSIONS: The infections by HPV9 strains and the economic burden of non-cervical HPV-related diseases in men were found to be the main drivers of direct costs.

Economic evaluation of the treatment of Acute Bacterial Skin and Skin Structure Infections (ABSSSIs) from the national payer perspective: introduction of a new treatment to the patient journey. A simulation of three European countries.

Background: The aim of this study was to develop a spending predictor model to evaluate the direct costs associated with the management of ABSSSIs from the National health-care provider's perspective of Italy, Romania, and Spain. Methodology: A decision-analytic model was developed to evaluate the diagnostic and clinical pathways of hospitalized ABSSSI patients based on scientific guidelines and real-world data. A Standard of Care (SoC) scenario was compared with a dalbavancin scenario in which the patients could be discharged early. The epidemiological and cost parameters were extrapolated from national administrative databases (i.e., hospital information system). A probabilistic sensitivity analysis (PSA) and one-way sensitivity analysis (OWA) were performed. Results: Overall, the model estimated an average annual number of patients with ABSSSIs of approximately 50,000 in Italy, Spain, and Romania. On average, the introduction of dalbavancin reduced the length of stay by 3.3 days per ABSSSI patient. From an economic perspective, dalbavancin did not incur any additional cost from the National Healthcare perspective, and the results were consistent among the countries. The PSA and OWA demonstrated the robustness of these results. Conclusion: This model represents a useful tool for policymakers by providing information regarding the economic and organizational consequences of an early discharge approach in ABSSSI management.

Rationale and budget impact of bimonthly use of Cetuximab in patients with recurrent and/or metastatic head and neck cancer.

BACKGROUND: In recurrent and/or metastatic head and neck squamous cell cancer, Cetuximab is administered once a week, followed by weekly doses. We present the clinical rationale of a different schedule of maintenance Cetuximab and we estimate the potential economic benefits on the health care budget from a societal perspective in Italy. METHODS: A budget impact (BI) excel-based model was developed comparing a base case scenario of 100% weekly administration with a dose of 250 mg/m2 to an every-other-week (EOW) administration at 50% or 100% with a dose of 500 mg/m2 . RESULTS: In the EOW, 50% scenario it was calculated a cost reduction of €347 000 of which 70% attributable to indirect costs, increasing to €694 000 after 4 months. CONCLUSIONS: In our analysis, we showed that this simplified schedule could also reduce the costs of treatments both for the health system (direct costs) and for the society (indirect costs).

Probabilistic cost-effectiveness analysis of controlled ovarian stimulation with recombinant FSH plus recombinant LH vs. human menopausal gonadotropin for women undergoing IVF.

BACKGROUND: The association of recombinant FSH plus recombinant LH in 2:1 ratio may be used not only to induce ovulation in anovulatory women with hypogonadotropic hypogonadism but also to achieve multiple follicular developments in human IVF. The aim of this analysis was to estimate the cost-effectiveness of Controlled Ovarian Stimulation (COS) with recombinant FSH (rFSH) plus recombinant LH (rLH) in comparison with highly purified human menopausal gonadotropin (HP-hMG) in the woman undergoing in vitro fertilization (IVF) in Italy. METHODS: A probabilistic decision tree was developed to simulate patients undergoing IVF, either using r-FSH + r-LH or HP-hMG to obtain COS. The model considers the National Health System (NHS) perspective and a time horizon equal to two years. Simulations were reported considering the number of retrieved oocytes (5-9, 10-15 and > 15) and transition probabilities were estimated through specific analyses carried out on the population of 848 women enrolled in the real-life. RESULTS: The model estimated that patients undertaking therapeutic protocol with r-FSH + r-LH increase the general success rate (+ 6.6% for pregnancy). The incremental cost-effectiveness ratio (ICER) per quality-adjusted life year (QALY) of r-FSH + r-LH was below the willingness to pay set at €20,000 for all the considered scenarios. CONCLUSIONS: The cost-utility analysis demonstrated that the r-FSH + r-LH is a cost-effective option for the Italian National Health System (NHS).

Economic burden of diverticular disease: An observational analysis based on real world data from an Italian region.

INTRODUCTION: Diverticular disease (DD), a herniation of the colonic mucosa through the muscle layer, covers a wide variety of conditions associated with the presence of diverticula in the colon. The most serious form is an acute episode of diverticulitis, which can lead to hospitalization and surgery with various types of consequences. The main aim of this study is to evaluate the economic burden of hospitalizations arising from acute episodes of diverticulitis using data from the administrative databases used in the Marche region in Italy and, as a secondary objective of this real-world data analysis, to study patient outcome variables following initial hospitalization for diverticulitis. METHOD: A deterministic linkage was performed at individual user level between the different administrative sources of the Marche region through anonymous ID number for a period of analysis between 1 January, 2008 and 31 December, 2014. We enrolled all patients with at least one hospitalization for "diverticulitis of the colon without mention of haemorrhage" (ICD-9-CM code 562.11) or "diverticulitis of the colon with haemorrhage" (ICD-9-CM code 562.13) as primary or secondary diagnosis. For each patient we assessed the cost of hospitalization, of medicines and of specialist services considering a time-scale of one year or cohort analysis 365days after first admission. RESULTS: The total number of residents in the Marche region who had at least one hospitalization for diverticulitis in the period 2008-2014 was 2987 (427 patients a year, corresponding to about 35 patients per 100,000 adult residents); the total number of admissions was 3453 (just over 490 a year). The direct healthcare costs incurred by the Marche region for episodes of diverticulitis in 2008-2014 amounted to approximately €11.4 million (€1.6 million a year), of which €10.9 million (95.5%) for the hospitalizations, € 246,000 (2.1%) for pharmaceutical treatment and €270,000 (2.4%) for specialist outpatient services. The average annual cost per patient was €3826, of which €3653 was for hospitalization, while pharmaceutical expenditure and specialist services accounted for €83 and €90, respectively. The cohort of patients undergoing a first admission for diverticulitis between 2010 and 2013 was made up of 1729 people (54.4% women, mean age 68.9 years), of whom 1500 (86.8%) did not undergo surgery while in hospital. Hospital mortality, recorded only for the over-65 age class, averaged 1.2%; for patients not receiving surgery during the initial hospitalization it was 0.5%, reaching 5.2% in patients undergoing surgery. The percentage of patients with one or more readmissions for diverticulitis within a year of the first was on average 7.8% and in 48% of cases this resulted in surgery. CONCLUSIONS: Our study is the first analysis in Italy to use real-world data to measure the financial impact of diverticular disease. Assuming that the diagnostic and therapeutic behaviour identified in the Marche region could be representative of the situation nationwide, the estimated annual number of hospitalizations in Italy for acute episodes of diverticulitis is 19,000. The total amount of economic resources needed to treat patients suffering from acute episodes of diverticulitis is estimated at €63.5 million a year.

Treatment plan comparison in acute and chronic respiratory tract diseases: an observational study of doxophylline vs. theophylline.

BACKGROUND: The main objective of this article is to estimate the global cost related to the use of the two drugs (associated drugs, specialist visits, hospital admissions, plasma drug monitoring). METHODS: The drug prescriptions were extracted from the Information System of the Pharmaceutical Prescriptions of the Marche Region for each ATC code in the years 2008-2012 and the number of patients per year and other outcomes measure were obtained. RESULTS: 13,574 patients were treated with theophylline and 19,426 patients with doxophylline. The number of patients treated was approximately 5,000 per year. Co-prescription with other drugs, use of corticosteroids, mean number of visits and hospital admissions (per 100 patients) were lower for doxophylline vs theophylline (1.55vs5.50, 0.3vs0.7, 2.05vs3.73 and 1.57vs3.3 respectively). The annual mean cost per patient was €187.4 for those treated with doxophylline and €513.5 for theophylline. CONCLUSIONS: In our study, doxophylline resulted to be associated with a reduction of the overall cost.

Economic aspects in the management of diabetes in Italy.

BACKGROUND: Diabetes mellitus (DM) is a chronic-degenerative disease associated with a high risk of chronic complications and comorbidities. The aim of this study is to estimate the average annual cost incurred by the Italian National Health Service (NHS) for the treatment of DM stratified by patients' comorbidities. Moreover, the model estimates the economic impact of implementing good clinical practice for the management of patients with DM. METHODS: Data were extrapolated from administrative database of the Marche Region and specific inclusion and exclusion criteria were developed from a clinical board in order to estimate patients with DM only, DM+1, DM+2, DM+3 and DM+4 comorbidities (cardiovascular disease, neuropathy, nephropathy and retinopathy). Regional data were considered a good proxy for implementing a previously developed cost-of-illness (COI) model from Italian NHS perspective already published. A scenario analysis was considered to estimate the economic impact of good clinical practice implementation in the treatment of DM and its comorbidities in Italy. RESULTS: The model estimated an average number of patients with DM per year in the Marche region of 85.909 (5.5% of population) from 2008 to 2011. The mean costs per patients with DM only, DM+1, DM+2, DM+3 and DM+4 comorbidities were €341, €1,335, €2,287, €5,231 and €7,085 respectively. From the Italian NHS perspective, the total economic burden of DM in Italy amounted to €8.1. billion/year (22% for drugs, 74% for hospitalization and 4% for visits). Scenario analysis demonstrates that the implementation of good clinical practice could save over €700 million per year. CONCLUSIONS: This model is the first study that considers real world data and COI model to estimate the economic burden of DM and its comorbidities from the Italian NHS perspective. Integrated management of the patients with DM could be a good driver for the reduction of the costs of this disease in Italy.

Health Data Entanglement and artificial intelligence-based analysis: a brand new methodology to improve the effectiveness of healthcare services.

Healthcare expenses will be the most relevant policy issue for most governments in the EU and in the USA. This expenditure can be associated with two major key categories: demographic and economic drivers. Factors driving healthcare expenditure were rarely recognised, measured and comprehended. An improvement of health data generation and analysis is mandatory, and in order to tackle healthcare spending growth, it may be useful to design and implement an effective, advanced system to generate and analyse these data. A methodological approach relied upon the Health Data Entanglement (HDE) can be a suitable option. By definition, in the HDE a large amount of data sets having several sources are functionally interconnected and computed through learning machines that generate patterns of highly probable future health conditions of a population. Entanglement concept is borrowed from quantum physics and means that multiple particles (information) are linked together in a way such that the measurement of one particle's quantum state (individual health conditions and related economic requirements) determines the possible quantum states of other particles (population health forecasts to predict their impact). The value created by the HDE is based on the combined evaluation of clinical, economic and social effects generated by health interventions. To predict the future health conditions of a population, analyses of data are performed using self-learning AI, in which sequential decisions are based on Bayesian algorithmic probabilities. HDE and AI-based analysis can be adopted to improve the effectiveness of the health governance system in ways that also lead to better quality of care.

HCV - Estimation of the number of diagnosed patients eligible to the new anti-HCV therapies in Italy.

OBJECTIVE: The present research wants to take a picture of the current epidemiological scenario regarding HCV infection in Italy. Studies used to estimate HCV burden of illness in Italy were so far local and performed a number of years ago, not mirroring the state of the art. EpaC wanted to provide a real number of diagnosed patients, eligible to new anti-HCV therapies. PATIENTS AND METHODS: EpaC is the most important Italian NGO for hepatopathic patients. A number of sources were cross-checked. Starting from all regional data regarding HCV-related exemptions, a correction/integration was performed with online questionnaire to associated patients (from which we derived patients cured and also other/no exemptions); survey to all prescribing centers in Italy (from which we derived the percentage of ineligible patients); prevalence of particular subpopulations was also collected (prisoners and HIV/HCV coinfected); calculations of new diagnosed, dead and cured patients in 2015. Excluded patients were illegal immigrants and active drug addicts (subpopulations currently rarely cured). RESULTS: A total of 221,549 patients were derived from regional exemptions databases and the mean national prevalence was 0.364%. Adding patients without exemptions/other exemptions, total was 308,624. We deducted the yearly deaths, cured and not eligible patients and, last, integrated with coinfected and prisoner special groups. Prevalence was also estimated at regional level, highlighting a reduction of the typical North-to-South prevalence gradient. Applying the above-mentioned corrections/integrations, total diagnosed and eligible HCV patients in Italy who can be immediately cured are supposed to range 163,148-187,756. CONCLUSIONS: This is a research aimed at filling an informative gap able to provide useful actual information in terms of HCV patients real-life management and future resource allocation. These data may be considered the basis for policy- and decision-makers to plan and manage patients ready to be cured. The research does not provide information on patients not yet diagnosed.

The direct and indirect cost of diabetes in Italy: a prevalence probabilistic approach.

INTRODUCTION: Diabetes mellitus is a chronic degenerative disease associated with a high risk of chronic complications and comorbidities. However, very few data are available on the associated cost. The objective of this study is to identify the available information on the epidemiology of the disease and estimate the average annual cost incurred by the National Health Service and Society for the Treatment of Diabetes in Italy. METHODS: A probabilistic prevalence cost of illness model was developed to calculate an aggregate measure of the economic burden associated with the disease, in terms of direct medical costs (drugs, hospitalizations, monitoring and adverse events) and indirect costs (absenteeism and early retirement). A systematic review of the literature was conducted to determine both the epidemiological and economic data. Furthermore, a one-way and probabilistic sensitivity analysis with 5,000 Monte Carlo simulations was performed to test the robustness of the results and define a 95% CI. RESULTS: The model estimated a prevalence of 2.6 million patients under drug therapies in Italy. The total economic burden of diabetic patients in Italy amounted to €20.3 billion/year (95% CI €18.61 to €22.29 billion), 54% of which are associated with indirect costs (95% CI €10.10 to €11.62 billion) and 46% with direct costs only (95% CI €8.11 to €11.06 billion). CONCLUSIONS: This is the first study conducted in Italy aimed at estimating the direct and indirect cost of diabetes with a probabilistic prevalence approach. As might be expected, the lack of information means that the real burden of diabetes is partly underestimated, especially with regard to indirect costs. However, this is a useful approach for policy makers to understand the economic implications of diabetes treatment in Italy.

The economic burden of musculoskeletal disorders on the Italian social security pension system estimated by a Monte Carlo simulation.

The aim of the study is to estimate the pension costs incurred for patients with musculoskeletal disorders (MDs) and specifically with rheumatoid arthritis (RA) and ankylosing spondylitis (AS) in Italy between 2009 and 2012. We analyzed the database of the Italian National Social Security Institute (Istituto Nazionale Previdenza Sociale i.e. INPS) to estimate the total costs of three types of social security benefits granted to patients with MDs, RA and AS: disability benefits (for people with reduced working ability), disability pensions (for people who cannot qualify as workers) and incapacity pensions (for people without working ability). We developed a probabilistic model with a Monte Carlo simulation to estimate the total costs for each type of benefit associated with MDs, RA and AS. We also estimated the productivity loss resulting from RA in 2013. From 2009 to 2012 about 393 thousand treatments were paid for a total of approximately €2.7 billion. The annual number of treatments was on average 98 thousand and cost in total €674 million per year. In particular, the total pension burden was about €99 million for RA and €26 million for AS. The productivity loss for AR in 2013 was equal to €707,425,191 due to 9,174,221 working days lost. Our study is the fi rst to estimate the burden of social security pensions for MDs based on data of both approved claims and benefits paid by the national security system. From 2009 to 2012, in Italy, the highest indirect costs were associated with disability pensions (54% of the total indirect cost), followed by disability benefits (44.1% of cost) and incapacity pensions (1.8% of cost). In conclusion, MDs are chronic and highly debilitating diseases with a strong female predominance and very significant economic and social costs that are set to increase due to the aging of the population.

The economic burden of HCV-induced diseases in Italy. A probabilistic cost of illness model.

OBJECTIVE: The hepatitis C virus (HCV) induces several pathological conditions worldwide, with a substantial medical and economic burden. The objective of this study was to estimate the average annual cost incurred by the National Health Service (NHS), as well as society, due to HCV in Italy. METHODS: A probabilistic incidence-based cost of illness model was developed to estimate an aggregate measure of the economic burden associated with HCV-induced diseases either in terms of direct or indirect costs. Indirect costs were calculated on the basis of lost productivity according to the human capital approach. A systematic literature review was carried out to identify epidemiological and economic data which were used to inform the model. Furthermore, a one-way probabilistic sensitivity analysis with 5,000 Monte Carlo simulations was performed, in order to test the robustness of the results and define the proper 95% Confidence Interval (CE). RESULTS: Overall, the total economic burden associated with HCV-induced diseases was estimated in €1.06 billion (95%CI: €0.61-€1.63). A percentage of 60.6%  was associated with indirect costs (95% CI: €0.37-€0.99 billion) and 39.4% with direct costs (95% CI: €0.23-€0.65 billion). In chronic hepatitis C, cirrhosis, hepatocellular carcinoma (HCC), liver transplantation and HCV-induced deaths, an average annual economic burden amounting to €0.26 (95%CI: €0.14-€0.41), €0.56 (95%CI: €0.30-€0.89), €0.051 (95%CI: €0.0007-€0.25), €0.05 (95%CI: €0.03-€0.08) and €0.15 (95%CI: €0.07-€0.27) billion respectively, was estimated. CONCLUSIONS: Italy is one of the European countries with the highest number of people affected by chronic HCV infection, the leading cause of cirrhosis, HCC and liver-related death. HCV-induced diseases generate high costs to Italian NHS. These highly debilitating and life-threatening complications generate a rather large amount of indirect costs for the Italian society as well.

Cost of poor adherence to anti-hypertensive therapy in five European countries.

The financial burden for EU health systems associated with cardiovascular disease (CV) has been estimated to be nearly €110 billion in 2006, corresponding to 10% of total healthcare expenditure across EU or a mean €223 annual cost per capita. The main purpose of this study is to estimate the costs related to hypertension and the economic impact of increasing adherence to anti-hypertensive therapy in five European countries (Italy, Germany, France, Spain and England). A probabilistic prevalence-based decision tree model was developed to estimate the direct costs of CV related to hypertension (CV defined as: stroke, heart attack, heart failure) in five European countries. Our model considered adherence to hypertension treatment as a main driver of blood pressure (BP) control (BP < 140/90 mmHg). Relative risk of CV, based on controlled or uncontrolled BP group, was estimated from the Framingham Heart Study and national review data. Prevalence and cost data were estimated from national literature reviews. A national payer (NP) perspective for 10 years was considered. Probabilistic sensitivity analysis was performed in order to evaluate uncertainty around the results (given as 95% confidence intervals). The model estimated a total of 8.6 million (1.4 in Italy, 3.3 in Germany, 1.2 in Spain, 1.8 in France and 0.9 in England) CV events related to hypertension over the 10-year time horizon. Increasing the adherence rate to anti-hypertensive therapy to 70% (baseline value is different for each country) would lead to 82,235 fewer CV events (24,058 in Italy, 7,870 in Germany, 18,870 in Spain, 24,855 in France and 6,553 in England). From the NP perspective, the direct cost associated with hypertension was estimated to be 51.3 billion (8.1 in Italy, 17.1 in Germany, 12.2 in Spain, 8.8 in France and 5.0 in England). Increasing adherence to anti-hypertensive therapy to 70% would save a total of 332 million (CI 95%: €319-346 million) from the NPs perspective. This study is the first attempt to estimate the economic impact of non-adherence amongst patients with diagnosed hypertension in Europe, using data from five European countries (Italy, France, Germany, Spain and England).

How can the results of Health Technology Assessment (HTA) evaluations applied to vaccinations be communicated to decision-makers and stakeholders? The ISPOR Rome Chapter Project.

HTA is considered the most comprehensive and transparent method of supporting decision-makers in their choices in Public Health. HTA on vaccines is being performed by many experts. However, they often present their studies to colleagues, but not to decisionmakers, who should be the main target and current users. It is therefore crucial to improve the transfer of scientific data to decision- makers and all stakeholders. The aims of the present project are: 1) to set up a team of experts to collect economic evaluations and HTA studies on vaccines and assess their actual use in decision-making processes; 2) to constitute regional working groups in order to identify the critical aspects of the communication process and identify the most appropriate method of data transfer. Systematic reviews of economic evaluations and HTA on vaccines and their actual use in decision-making will be used to draw up the basic documents for discussion by the 3 regional working boards. The working groups will discuss the current scientific evidence and communication methods and will try to implement a model of technology assessment with well-defined and objective criteria, in order to better fit pharmaco-economic and HTA methods to the field of vaccinations. Improving the transfer of HTA results to stakeholders, particularly decision-makers, will enable decisions to be taken on the basis of scientific evidence, and appropriate, sustainable actions to be undertaken.

The role of tumour necrosis factor in the pathogenesis of immune-mediated diseases.

Immune-mediated inflammatory diseases (IMIDs), such as rheumatoid arthritis, psoriatic arthritis, psoriasis, axial spondyloarthropathies, Crohn's disease, ulcerative colitis and juvenile idiopathic arthritis, comprise a group of chronic disorders characterized by an immune-mediated pathogenesis. Although at clinical presentation these diseases appear unrelated, they have been recognized to share similar pathogenic mechanisms. Data from epidemiological and genetic studies further support the concept that IMIDs are interrelated, as they can co-occur in the same patient and share a similar genetic susceptibility. The specific aetiologies of IMIDs remain unknown, but all are known to involve dysregulation of the immune system, including an over-expression of the pro-inflammatory cytokine tumour necrosis factor (TNF). The pivotal role played by TNF in the pathogenesis and pathophysiology of IMIDs has been documented by extensive preclinical and clinical investigations, and confirmed by the efficacy of anti-TNF biotechnological drugs, such as etanercept, infliximab and adalimumab, in the therapeutic management of these disorders. In this narrative review, we discuss the available data on the TNF-dependent pathogenesis of IMIDs and associations among the different disorders. Although much remains to be discovered about the pathogenesis and aetiology of IMIDs, their common inflammatory pathological features may explain why they can be successfully targeted by anti-TNF drugs. Among these, adalimumab, a fully human monoclonal antibody, has been approved for treatment of nine distinct IMID indications and it is likely to become a valuable therapeutic tool for this complex cluster of chronic inflammatory disorders.

anti-TNF agents as therapeutic choice in immune-mediated inflammatory diseases: focus on adalimumab.

The complex pathogenesis of immune-mediated inflammatory diseases (IMIDs) has been extensively investigated and dysregulation of cytokines, such as tumour necrosis factor (TNF) has been shown to play a dominant role in the pathogenesis of various IMIDs, such as rheumatoid arthritis, ankylosing spondylitis, Crohn's disease, ulcerative colitis, psoriasis and psoriatic arthritis. The subsequent development of biological agents capable of blocking TNF has led to important advances in the pharmacotherapy of such diseases and confirmed the concept of a common pathophysiology among IMIDs with TNF having a predominant role. Five TNF inhibitors have currently been approved for treatment of one or more IMIDs; these include infliximab, etanercept, adalimumab, golimumab and certolizumab pegol. Given the similarities in the pathogenic background of IMIDs, one could expect that anti-TNF agents be similarly effective and with comparable tolerability profiles; however, this may not be the case. Structural and pharmacological differences among the anti-TNF drugs are likely to result in differences in efficacy and tolerability among the agents in the different IMIDs, together with differences in potency, therapeutic dose ranges, dosing regimens, administration routes, and propensity for immunogenicity. Among the five TNF inhibitors approved for treatment of IMIDs, adalimumab has the widest range of indications. Data from controlled clinical trials of adalimumab, showing its excellent efficacy and tolerability in a wide range of indications, are supported by real-world long-term data from observational studies, which confirm the value of adalimumab as a suitable choice in the management of IMIDs.

Adalimumab in the treatment of immune-mediated diseases.

Tumour necrosis factor (TNF) plays an important role in the pathogenesis of immune-mediated inflammatory diseases (IMIDs). TNF inhibition results in down-regulation of abnormal and progressive inflammatory processes, resulting in rapid and sustained clinical remission, improved quality of life and prevention of target organ damage. Adalimumab is the first fully human monoclonal antibody directed against TNF. In this article, we review the role and cost effectiveness of adalimumab in the treatment of IMIDs in adults and children. The efficacy and tolerability of adalimumab has been demonstrated in patients with a wide range of inflammatory conditions, leading to regulatory approval in rheumatoid arthritis (RA), psoriatic arthritis (PsA), plaque psoriasis, inflammatory bowel diseases (Crohn's disease, ulcerative colitis, paediatric Crohn's disease, and intestinal Behçet's disease), ankylosing spondylitis (AS), axial spondyloarthritis (SpA) and juvenile idiopathic arthritis. The major tolerability issues with adalimumab are class effects, such as injection site reactions and increased risk of infection and lymphoma. As with all anti-TNF agents, adalimumab is immunogenic, although less than infliximab, and some patients receiving long-term adalimumab will develop anti-drug antibodies, causing a loss of response. Comparisons of its clinical utility and cost effectiveness have shown it to be a valid treatment choice in a wide range of patients. Recent data from Italian economic studies show the cost effectiveness of adalimumab to be below the threshold value for health care interventions for most indications. In addition, analysis of indirect costs shows that adalimumab significantly reduces social costs associated with RA, PsA, AS, Crohn's disease and psoriasis. The fact that adalimumab has the widest range of approved indications, many often presenting together in the same patient due to the common pathogenesis, may further improve the utility of adalimumab. Current clinical evidence shows adalimumab to be a valuable resource in the management of IMIDs. Further research, designed to identify patients who may benefit most from this drug, will better highlight the role and cost-effectiveness of this versatile TNF inhibitor.