Switching patterns of biological drugs in patients with psoriasis and psoriatic arthritis: insight from the VALORE database network.

BACKGROUND: Switch patterns among different biologics and from originators to biosimilars (and vice versa) can be complex in patients with psoriasis (PsO) and psoriatic arthritis (PsA). OBJECTIVE: The aim of this study was to describe switching patterns of biological drugs in PsO/PsA patients and to explore predictors of multiple switches and switch-back. RESEARCH DESIGN AND METHODS: A large-scale retrospective cohort study was conducted using the Italian VALORE database. Bio-naïve users treated for PsO/PsA during 2010-2022 were included. Time to switch/swap and predictors of multiple switches and switch-back were analyzed. RESULTS: Thirty-thousand seven hundred bio-naïve users were included. At 3 and 5 years of follow-up, patients with at least one switch/swap were 37.1% and 47.8%, respectively. The median time to first switch/swap was significantly shorter (p< 0.001) for TNF-α inhibitors (2,068 days) than anti-IL (2,780 days). At 1 year of follow-up patients starting with IL-23 switched/swapped biological therapy less frequently than those with anti-IL-12/23 and anti-IL-17 (4.9% vs. 8.7% and 9.4%, respectively). Patients starting with anti-IL-12/23 reported a significantly lower risk of multiple switches and switch-back (0.74, 95% CI, 0.67-0.83; 0.58, 95% CI, 0.44-0.77, respectively) than those with TNF-α inhibitors. CONCLUSIONS: Patients with PsO/PsA starting with TNF-α inhibitors switch/swap more rapidly and frequently than those with anti-IL, which are also associated with a reduced risk of multiple switches during follow-up.

An epidemiological investigation of high-risk infants for Respiratory Syncytial Virus infections: a retrospective cohort study.

BACKGROUND: Respiratory Syncytial Virus (RSV) infections may lead to severe consequences in infants born preterm with breathing problems (such as bronchopulmonary dysplasia (BPD) and respiratory distress syndrome (RDS)) or congenital heart diseases (CHD). Since studies investigating the influence of different gestational age (WGA) and concomitant specific comorbidities on the burden of RSV infections are scarce, the present study aimed to better characterize these high-risk populations in the Italian context. METHODS: This retrospective, longitudinal and record-linkage cohort study involved infants born between 2017 and 2019 in Lazio Region (Italy) and is based on data extracted from administrative databases. Each infant was exclusively included in one of the following cohorts: (1) BPD-RDS (WGA ≤35 with or without CHD) or (2) CHD (without BPD and/or RDS) or (3) Preterm (WGA ≤35 without BPD (and/or RDS) or CHD). Each cohort was followed for 12 months from birth. Information related to sociodemographic at birth, and RSV and Undetermined Respiratory Agents (URA) hospitalizations and drug consumption at follow-up were retrieved and described. RESULTS: A total of 8,196 infants were selected and classified as 1,084 BPD-RDS, 3,286 CHD and 3,826 Preterm. More than 30% of the BPD-RDS cohort was composed by early preterm infants (WGA ≤ 29) in contrast to the Preterm cohort predominantly constitute by moderate preterm infants (98.2%), while CHD infants were primarily born at term (83.9%). At follow-up, despite the cohorts showed similar proportions of RSV hospitalizations, in BPD-RDS cohort hospitalizations were more frequently severe compared to those occurred in the Preterm cohort (p<0.01), in the BPD-RDS cohort was also found the highest proportion of URA hospitalizations (p<0.0001). In addition, BPD-RDS infants, compared to those of the remaining cohorts, received more frequently prophylaxis with palivizumab (p<0.0001) and were more frequently treated with adrenergics inhalants, and glucocorticoids for systemic use. CONCLUSIONS: The assessment of the study clinical outcomes highlighted that, the demographic and clinical characteristics at birth of the study cohorts influence their level of vulnerability to RSV and URA infections. As such, continuous monitoring of these populations is necessary in order to ensure a timely organization of health care system able to respond to their needs in the future.

Comparing clinical trial population representativeness to real-world users of 17 biologics approved for immune-mediated inflammatory diseases: An external validity analysis of 66,639 biologic users from the Italian VALORE project.

To date, no population-based studies have specifically explored the external validity of pivotal randomized clinical trials (RCTs) of biologics simultaneously for a broad spectrum of immuno-mediated inflammatory diseases (IMIDs). The aims of this study were, firstly, to compare the patients' characteristics and median treatment duration of biologics approved for IMIDs between RCTs' and real-world setting (RW); secondly, to assess the extent of biologic users treated for IMIDs in the real-world setting that would not have been eligible for inclusion into pivotal RCT for each indication of use. Using the Italian VALORE distributed database (66,639 incident biologic users), adult patients with IMIDs treated with biologics in the Italian real-world setting were substantially older (mean age ± SD: 50 ± 15 years) compared to those enrolled in pivotal RCTs (45 ± 15 years). In the real-world setting, certolizumab pegol was more commonly used by adult women with psoriasis/ankylosing spondylitis (F/M ratio: 1.8-1.9) compared to RCTs (F/M ratio: 0.5-0.6). The median treatment duration (weeks) of incident biologic users in RW was significantly higher than the duration of pivotal RCTs in almost all indications for use and most biologics (4-100 vs. 6-167). Furthermore, almost half (46.4%) of biologic users from RW settings would have been ineligible for inclusion in the respective indication-specific pivotal RCTs. The main reasons were: advanced age, recent history of cancer and presence of other concomitant IMIDs. These findings suggest that post-marketing surveillance of biologics should be prioritized for those patients.

Pattern of care of brain tumor patients in the last months of life: analysis of a cohort of 3045 patients in the last 10 years.

BACKGROUND: End-of-life in patients with brain cancer presents special challenges, and palliative care approach is underutilized. Patients with brain cancer, in the last months of life, receive frequent hospital readmissions, highlighting bad end-of-life care quality. Early integration of palliative care improves quality of care in advanced stage of disease and patient's quality of death. PURPOSE: We retrospectively analyzed a consecutive series of patients with brain cancer discharged after diagnosis to evaluate pattern of treatment and rate of hospital readmission in the last months of life. DESIGN: Data were collected from the Lazio Region Healthcare database. SETTING: Adult patients discharged with diagnosis ICD-9 191.* between January 1, 2010, and December 31, 2019 were included. RESULTS: A total of 6672 patients were identified, and 3045 deaths were included. In the last 30 days 33% were readmitted to the hospital and 24.2% to the emergency room. 11.7% were treated with chemotherapy and 6% with radiotherapy. Most indicators of end-of-life care showed wide variability by hospital of discharge. CONCLUSIONS: Strategies to improve quality of care at the end of life and to decrease re-hospitalization and futile treatments are becoming increasingly important to improve quality of death and reduce healthcare costs. Variability observed by hospital of discharge indicates the lack of a standard approach to end-of-life care.

Impact of COVID-19 pandemic on outpatient visit volume in cancer patients: Results of COMETA multicenter retrospective observational study.

Objective: To evaluate the impact of the COVID-19 pandemic on first and follow-up visits for cancer outpatients. Methods: This is a multicenter retrospective observational study involving three Comprehensive Cancer Care Centers (CCCCs): IFO, including IRE and ISG in Rome, AUSL-IRCCS of Reggio Emilia, and IRCCS Giovanni Paolo II in Bari) and one oncology department in a Community Hospital (Saint'Andrea Hospital, Rome). From 1 January 2020 and 31 December 2021, we evaluated the volume of outpatient consultations (first visits and follow-up), comparing them with the pre-pandemic year (2019). Results were analyzed by quarter according to the Rt (real-time indicator used to assess the evolution of the pandemic). IFO and IRCCS Giovanni Paolo II were "COVID-free" while AUSL-IRCCS RE was a "COVID-mixed" Institute. Depending on the Rt, Sain't Andrea Hospital experienced a "swinging" organizational pathway (COVID-free/ COVID-mixed). Results: Regarding the "first appointments", in 2020 the healthcare facilities operating in the North and Center of Italy showed a downward trend. In 2021, only AUSL-IRCCS RE showed an upward trend. Regarding the "follow-up", only AUSL IRCCS RE showed a slight up-trend in 2020. In 2021, IFO showed an increasing trend, while S. Andrea Hospital showed a negative plateau. Surprisingly, IRCCS Giovanni Paolo II in Bari showed an uptrend for both first appointment and follow-ups during pandemic and late pandemic except for the fourth quarter of 2021. Conclusions: During the first pandemic wave, no significant difference was observed amongst COVID-free and COVID-mixed Institutes and between CCCCs and a Community Hospital. In 2021 ("late pandemic year"), it has been more convenient to organize COVID-mixed pathway in the CCCCs rather than to keep the Institutions COVID-free. A swinging modality in the Community Hospital did not offer positive results in term of visit volumes. Our study about the impact of COVID-19 pandemic on visit volume in cancer outpatients may help health systems to optimize the post-pandemic use of resources and improve healthcare policies.

Methodology of the brodalumab assessment of hazards: a multicentre observational safety (BRAHMS) study.

INTRODUCTION: Safe and effective pharmacological treatment is of paramount importance for treating severe psoriasis. Brodalumab, a monoclonal antibody against interleukin (IL) 17 receptor A, was granted marketing authorisation in the EU in 2017. The European Medicines Agency requested a postauthorisation safety study of brodalumab to address potential safety issues raised during drug development regarding major adverse cardiovascular events, suicidal conduct, cancer and serious infections. METHODS AND ANALYSIS: BRodalumab Assessment of Hazards: A Multinational Safety is a multicentre observational safety study of brodalumab running from 2017 to 2029 using population-based healthcare databases from Denmark, Sweden, Norway, Netherlands, Germany and three different centres in Italy. A distributed database network approach is used, such that only aggregate data are exchanged between sites.Two types of designs are used: a case-time-control design to study acute effects of transient treatment and a variation of the new user active comparator design to study the effects of transient or chronic treatment. As comparators, inhibitors of TNF-α, inhibitors of IL-12 and IL-23, and other inhibitors of cytokine IL-17A are included.In the self-controlled case-time-control design, the risk of developing the outcome of interest during periods of brodalumab use is compared within individuals to the risk in periods without use.In the active comparator cohort design, new users of brodalumab are identified and matched to new users of active comparators. Potential baseline confounders are adjusted for by using propensity score modelling. For outcomes that potentially require large cumulative exposure, an adapted active comparator design has been developed. ETHICS AND DISSEMINATION: The study is approved by relevant authorities in Denmark, Norway, Sweden, the Netherlands, Germany and Italy in line with the relevant legislation at each site. Data confidentiality is secured by the distributed network approach. Results will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: EUPAS30280.

Development of Approaches and Metrics to Measure the Impact and Improve the Clinical Outcomes of Patients With Frailty in the Era of COVID-19. The COMETA Italian Protocol.

The outbreak of the coronavirus 2 disease 2019 (COVID-19) puts an enormous burden on healthcare systems worldwide. This may worsen outcomes in patients with severe chronic diseases such as cancer, autoimmune diseases, and immune deficiencies. In this critical situation, only a few available data exist, which do not allow us to provide practical guides for the treatment of oncological or immunocompromised patients. Therefore, a further step forward is needed, addressing the specific needs and demands of frail patients in the pandemic era. Here we aim to present a protocol of a study approved by an ethical committee named "CO.M.E.TA". CO.M.E.TA protocol is a network project involving six Italian institutions and its goals are: i) to measure and compare the impact of the pandemic on the access of cancer and immunocompromised patients to therapies in three Italian regions; ii) to assess how reorganizational measures put in place in these different institutions have impacted specific metrics of performance; iii) to establish a COVID-19 Biobank of biological samples from SARS-CoV-2 infected patients to be used to study immunological alterations in patients with immune frailty.

Large-Scale Postmarketing Surveillance of Biological Drugs for Immune-Mediated Inflammatory Diseases Through an Italian Distributed Multi-Database Healthcare Network: The VALORE Project.

BACKGROUND: Biological drugs have improved the management of immune-mediated inflammatory diseases (IMIDs) despite being associated with important safety issues such as immunogenicity, infections, and malignancies in real-world settings. OBJECTIVE: The aim of this study was to explore the potential of a large Italian multi-database distributed network for use in the postmarketing surveillance of biological drugs, including biosimilars, in patients with IMID. METHODS: A retrospective cohort study was conducted using 13 Italian regional claims databases during 2010-2019. A tailor-made R-based tool developed for distributed analysis of claims data using a study-specific common data model was customized for this study. We measured the yearly prevalence of biological drug users and the frequency of switches between originator and biosimilars for infliximab, etanercept, and adalimumab separately and stratified them by calendar year and region. We then calculated the cumulative number of users and person-years (PYs) of exposure to individual biological drugs approved for IMIDs. For a number of safety outcomes (e.g., severe acute respiratory syndrome coronavirus 2 [SARS-COV-2] infection), we conducted a sample power calculation to estimate the PYs of exposure required to investigate their association with individual biological drugs approved for IMIDs, considering different strengths of association. RESULTS: From a total underlying population of almost 50 million inhabitants from 13 Italian regions, we identified 143,602 (0.3%) biological drug users, with a cumulative exposure of 507,745 PYs during the entire follow-up. The mean age ± standard deviation of biological drug users was 49.3 ± 16.3, with a female-to-male ratio of 1.2. The age-adjusted yearly prevalence of biological drug users increased threefold from 0.7 per 1000 in 2010 to 2.1 per 1000 in 2019. Overall, we identified 40,996 users of biosimilars of tumor necrosis factor (TNF)-α inhibitors (i.e., etanercept, adalimumab, and infliximab) in the years 2015-2019. Of these, 46% (N = 18,845) switched at any time between originator and biosimilars or vice versa. To investigate a moderate association (incidence rate ratio 2) between biological drugs approved for IMIDs and safety events of interest, such as optic neuritis (lowest background incidence rate 10.4/100,000 PYs) or severe infection (highest background incidence rate 4312/100,000 PYs), a total of 43,311 PYs and 104 PYs of exposure to individual biological drugs, respectively, would be required. As such, using this network, of 15 individual biological drugs approved for IMIDs, the association with those adverse events could be investigated for four (27%) and 14 (93%), respectively. CONCLUSION: The VALORE project multi-database network has access to data on more than 140,000 biological drug users (and > 0.5 million PYs) from 13 Italian regions during the years 2010-2019, which will be further expanded with the inclusion of data from other regions and more recent calendar years. Overall, the cumulated amount of person-time of exposure to biological drugs approved for IMIDs provides enough statistical power to investigate weak/moderate associations of almost all individual compounds and the most relevant safety outcomes. Moreover, this network may offer the opportunity to investigate the interchangeability of originator and biosimilars of several TNFα inhibitors in different therapeutic areas in real-world settings.

Determinants of first-line biological treatment in patients with rheumatoid arthritis: Results from an observational study.

ABSTRACT: Guidelines for the treatment of rheumatoid arthritis (RA) recommend the use of conventional synthetic disease modifying anti-rheumatic drugs (cs-DMARDs) at the onset of the disease and only in the case of therapeutic failure, the addition of a biological drug (b-DMARD) is suggested.The study aimed to evaluate determinants for first-line biological treatment in patients with RA in clinical practice.A cohort of patients with RA, resident in Lazio, a central Italian Region, where Rome is located, and with at least one disease modifying anti-rheumatic drugs (DMARD) prescription between 2010 and 2016 was selected using health information systems linkable with each other by an individual unique anonymous identifier. In particular RA cohort was defined retrieving all patients with at least a RA disease code in regional data claims (hospital discharge, exemption code, emergency department access, or therapeutic plan). Only new users were included and the first-line treatment was identified: cs-DMARD or b-DMARD.Descriptive analysis according to type of DMARD treatment was performed. Through multivariate logistic regression models (odds ratio [OR]; confidence interval [CI95%]) determinants of therapy such as age, comorbidity, and comedication were investigated.Finally, switching during the first year of treatment from cs-DAMARDs to b-DMARDs was analyzed.DMARD-new users with RA were 5641; 7.1% of them with b-DMARD as first-line treatment. Considering the year of dispensing, this percentage ranged from 4.9% (2011) to 8.2% (2015). Among cs-DMARD the most prescribed active agent was methotrexate (59.3%), while among b-DMARD it was etarnecept (37.0%), followed by adalimumab (21.2%). The average age of the cohort was 54 years with 77% of women. Determinants of first-line b-DMARD use were: age (OR<30vs>65 = 3.7; 2.6-5.2, OR[30-45)vs>65 = 1.7; 1.2-2.4, OR[45-55)vs>65 = 1.6; 1.1-2.4, OR[55-65)vs>65 = 1.2; 0.8-1.7), cancers (OR = 2.3; 1.3-4.2), cardio-cerebrovascular disease (OR = 1.4; 1.0-1.9), use of non-steroidal anti-inflammatory drugs (NSAIDs) (OR = 0.6; 0.4-0.7) and corticosteroids (OR = 0.6; 0.5-0.7) in the 6 months preceding diagnosis.In the first year of treatment, we observed a percentage of switch from cs-DMARDs to b-DMARDs of 7.9%.In clinical practice, about 7% of patients with RA are prescribed with a b-DMARD as first-line treatment. This therapeutic option, even if not supported by guide lines, is mostly link to younger age and clinical profile of the patients.

Real world data to identify target population for new CAR-T therapies.

PURPOSE: Diffuse large B-cell lymphoma (DLBCL) is an aggressive lymphoma often refractory to currently available treatments (immuno-chemotherapy/autologous-stem-cell-transplantation-ASCT). Recently, new cell therapies have been approved for patients failing two conventional treatments, CAR-T (Chimeric-Antigen-Receptor-T-cell), committing payers in planning and implementing their use. We aim to define, using Real World Data (RWD), a reproducible procedure that allows identification of CAR-T target population for DLBCL. METHODS: Through the linking of electronic healthcare datasets (EHD), we identified patients with non-Hodgkin's Lymphoma (NHL), resident in Lazio region (2010-2015), aged ≥20 years. DLBCL patients were followed using pathological anatomy (PA) reports, up to 3 years. To be defined as relapsed after two treatment lines, patients must have had new chemotherapy and/or NHL hospitalization after ASCT or at the end of the second chemotherapy. The incident rate of second relapse (R2-rate) was extended to the population without PA reports. RESULT: NHL incident patients were 7384, 68% presented a PA report and, 29% of these had DLBCL codes. Patients who relapsed after two treatment lines were 47 (39%) in the subgroup of patients who received ASCT and 138 (41%) in that with second chemotherapy treatment. Patients in the two subgroups were very different in terms of age and comorbidity. The annual incident number of DLBCL was estimated to be 329 which multiplied by R2-rate (13.7%) gives 45 patients per year eligible for CAR-T. DISCUSSION: This study shows how RWD allows the identification of a target population with new advanced therapies. This approach is rigorous, transparent and verifiable over time.

In Search of Predictors of Switching Between Erythropoiesis-Stimulating Agents in Clinical Practice: A Multi-Regional Cohort Study.

BACKGROUND AND OBJECTIVES: Switching between different erythropoiesis-stimulating agents (ESAs) during the first year of therapy is frequent (15-20%), much more so toward reference products than biosimilars. The objectives of this study were to investigate the frequency and identify the potential predictors of switching between biosimilar and originator ESAs during the first year of treatment in patients with chronic kidney disease (CKD), or chemotherapy-related anemia from six large Italian geographic areas in the years 2009-2015. METHODS: A retrospective cohort study was conducted using six Italian regional claims databases (≥ 13 million inhabitants) during 2009-2015. Among incident epoetin users, the frequency of single, multiple, and backward switch during the first year of treatment was evaluated. Using frailty Cox models, potential predictors of first switch were identified. All analyses were stratified by the main indications for use. RESULTS: Among 102,240 incident epoetin users, 15,853 (15.5%) switched to another epoetin during the first year of therapy; only 18% of these switched to biosimilars. Single switch was more common (62.2% of the switchers) than multiple (23.5%) or backward switch (14.3%). In cancer, the cumulative number of transfusions and iron preparations dispensed, as well as hyperparathyroidism, were predictors of switching. In CKD, the cumulative number of transfusions, number of vitamin A/D preparations dispensed, and CKD severity increased the probability of switching. CONCLUSIONS: Switching between ESAs was frequent in both CKD and cancer patients. The number of cumulative transfusions and severity of disease seemed to affect the switch.

[Appropriate use of trastuzumab in Lazio Region: therapeutic scenarios and estimation of possible savings for the Regional Health Service.] / Utilizzo appropriato del trastuzumab nel Lazio: scenari terapeutici e stima del possibile risparmio per il Servizio Sanitario Regionale.

BACKGROUND: The availability of subcutaneous (SC) and intravenous (EV) formulations of trastuzumab and the recent release of the biosimilar EV version (10/2018) increase the offer for the treatment of patients with breast or gastric cancer HER2 positive. In this context, it is necessary to build therapeutic scenarios form avalible data in order to estimate the potential savings for the Regional Health Service (RHS) taking into account the appropriateness of use and patient's preferences. AIM: To evaluate the available comparative evidence regarding the effectiveness and safety of the different trastuzumab formulations; to analyze the supply of trastuzumab by type of administration (EV/SC) in Lazio in 2018, identifying the most appropriate use; to hypothesize a cost-effective scenario for the Regional Health Service (SSR) in 2019. Mehods. With the working group formed by clinicians and methodologists, we analysed the evidence of efficacy and safety available to date for the different formulations of trastuzumab, also taking into account the recent availability of biosimilars and with particular regard to the phenomenon of the potential switch between different therapeutic options. In addition, for the year 2019 the available economic impact assessments were also simulated with data from the Lazio Region. Through the datas from direct pharmaceutical products, the transtuzumab cycles supplied in 2018 were identified separately for the available formulations (EV/SC). For each cycle of therapy, starting from the date of delivery, the possible presence of a concomitant treatment (± 2 days) was investigated, tracing the type and method of administration. The treatments (concomitant with trastuzumab) were identified for which there were conflicting modes of administration. In addition, the supply of SC per dispensing structure was evaluated and, on the basis of this information, a scenario of use was hypothesized that takes into account costs and plausible consumption. RESULTS: A review of the literature summarized the available evidence on the efficacy and safety of the use of trastuzumab in the recorded therapeutic indications. The review was discussed with the working group and used to reproduce, at regional level, the estimates of the economic impact of the different therapeutic choices possible with trastuzumab. As regards the data on the use of trastuzumab, in the Lazio Region in 2018, 22,214 treatment cycles were observed (at a cost of 33 million euro) for 2,407 patients; new users accounted for 52.2%. 46.8% of the cycles were administered via SC; the use of the biosimilar was observed from October onwards and involved 143 cycles (0.6%). In 68.4% of the cycles trastuzumab was administered in monotherapy; among the therapies associated with trastuzumab, the most frequent was pertuzumab (n=4,258, 19.2% of the total cycles), followed by paclitaxel (n=1,364, 6.1% of the total cycles). Among the cycles of trastuzumab in concomitant therapy (N=7,022), 17.3% was administered via SC despite the presence of other drugs administered via EV. The prescriptive pattern of trastuzumab was heterogeneous for the different delivery structures. The SC administration presents a variability in the supply from 26% to 70% (interquartile range) and does not seem to be related to the type and volume of activity of the hospital. If the biosimilar EV is expected to account for 55% of consumption by 2019, thus reducing the use of the EV originator to 10% and the SC originator to 35%, savings of more than €7 million. CONCLUSIONS: Through the use data of the different formulations available for trastuzumab and taking into account the prescriptive appropriateness (and patient preferences), it has been possible to identify a SSR scenario of economic convenience due to the greater use of the biosimilar.

Neonatal outcomes following new reimbursement limitations on palivizumab in Italy.

OBJECTIVE: To evaluate the impact of new reimbursement decisions for palivizumab treatment on respiratory syncytial virus (RSV) hospitalisations and the concomitant number of palivizumab prescriptions for infants aged <2 years. DESIGN: We compared the RSV hospitalisation rates in infants before and after implementation of new limitations during three RSV seasons 2014-2017. SETTING: Population aged <2 years at the beginning of each RSV seasons extracted from regional health systems (Lazio region, 2016, 5 898 124 inhabitants and 47 595 births). PATIENTS: Out of 70 323 infants, 5895 (8.4%) premature babies (gestational age (GA) <37 weeks) were followed before-after Italian Medicines Agency (AIFA)-2016 limitations. INTERVENTION: In 2016, AIFA, following the American Academy of Pediatrics guidelines, decided to limit coverage of palivizumab prophylaxis (GA ≤29 weeks). MAIN OUTCOMES MEASURES: Trend of hospitalisations by months and rate of RSV before-after new restrictions were analysed. Palivizumab prescriptions and costs for National Health Service (NHS) were considered. RESULTS: In a population of 284 902 aged <2 years, the number of hospitalisations due to RSV infection was 1729. Following AIFA-2016 limitations, a reduction in the number of RSV infection-based hospitalisations from 6.3/1000 (95% CI 6.0 to 6.7) to 5.5/1000 (95% CI 5.0 to 5.9) was observed. Palivizumab showed a concomitant reduction of 48% in the number of prescriptions (saving €750 000 for the NHS). No differences of GA, age on admission or severity of RSV infection were observed. CONCLUSIONS: Implementation of the new palivizumab reimbursement criteria was not associated with an increase in the RSV hospitalisation rate for children aged <2 years despite a significant reduction in the number of palivizumab prescriptions.

Comparative effectiveness and safety of erythropoiesis-stimulating agents (biosimilars vs originators) in clinical practice: a population-based cohort study in Italy.

OBJECTIVES: To evaluate the benefit/risk profile of epoetin α biosimilar with the erythropoiesis-stimulating agents (ESAs) originators when administered to naïve patients from clinical practice. DESIGN: Population-based observational cohort study. SETTING: All residents in the Lazio Region, Italy, with chronic kidney disease (CKD) or cancer retrieved from the Electronic Therapeutic Plan (ETP) Register for ESA between 2012 and 2014. PARTICIPANTS: Overall, 13 470 incident ESA users were available for the analysis, 8161 in the CKD and 5309 in the oncology setting, respectively. INTERVENTIONS: ESAs identified through the ATC B03XA were divided into 3 groups: (1) biosimilars; (2) epoetin α originator and (3) other originators. Patients were exposed to ESAs from the date of activation of the ETP, until the end of a 6-month follow-up period. OUTCOME MEASURES: Effectiveness (all-cause mortality and blood transfusion) and safety (major cardiovascular events, blood dyscrasia). A composite outcome including all-cause mortality, blood transfusion and major cardiovascular events was predefined. HRs of any outcome were estimated through Cox regression. RESULTS: We found no differences between patients on biosimilars or all originators with regard to the risk estimates of all-cause mortality, blood transfusion, major cardiovascular events and blood dyscrasia in the CKD setting. The composite outcome confirmed these results (biosimilars vs epoetin α originators: adjusted HR=1.02, 95% CI 0.78 to 1.33; biosimilars vs other originators: adjusted HR=1.09, 95% CI 0.85 to 1.41). Comparable risk estimates were observed between biosimilars and all originators in the oncology setting. CONCLUSIONS: In both settings, our findings are suggestive of no difference between biosimilars and originators on relevant effectiveness and safety outcomes. This study may contribute to settling future drug policy for the health services and provides reassurance on the approval pathway for biosimilars. The oncology setting merits further research, taking into account tumour types, tumour stage and anticancer chemotherapy administered.

Effects of socioeconomic position on 30-day mortality and wait for surgery after hip fracture.

OBJECTIVE: In countries where the National Health Service provides universal health coverage, socioeconomic position should not influence the quality of health care. We examined whether socioeconomic position plays a role in short-term mortality and waiting time for surgery after hip fracture. DESIGN: Retrospective cohort study. SETTING: and participants From the Hospital Information System database, we selected all patients, aged at least 65 years and admitted to acute care hospitals in Rome for a hip fracture between 1 January 2006 and 30 November 2007. The socioeconomic position of each individual was obtained using a city-specific index of socioeconomic variables based on the individual's census tract of residence. MAIN OUTCOME MEASURES: Three different outcomes were defined: waiting times for surgery, mortality within 30 days and intervention within 48 h of hospital arrival for hip fracture. We used a logistic regression to estimate 30-day mortality and a Cox proportional hazard model to calculate hazard ratios of intervention within 48 h. Median waiting times were estimated by adjusted Kaplan-Meyer curves. Analyses were adjusted for age, gender and coexisting medical conditions. RESULTS: Low socioeconomic level was significantly associated with higher risk of mortality [adjusted relative risk (RR) = 1.51; P < 0.05] and lower risk of early intervention (adjusted RR = 0.32; P < 0.001). Socioeconomic level had also an effect on waiting times within 30 days. CONCLUSIONS: Individuals living in disadvantaged census tracts had poorer prognoses and were less likely than more affluent people to be treated according to clinical guidelines despite universal healthcare coverage.

Risk of fatal overdose during and after specialist drug treatment: the VEdeTTE study, a national multi-site prospective cohort study.

BACKGROUND: Specialist drug treatment is critical to overdose prevention; methadone maintenance is effective, but we lack evidence for other modalities. We evaluate the impact of a range of treatments for opiate dependence on overdose mortality. METHODS: Prospective cohort study of 10,454 heroin users entering treatment 1998-2001 in Italy followed-up for 10,208 person-years in treatment and 2,914 person-years out of treatment. Standardized overall mortality ratios (SMR) estimate excess mortality risk for heroin users in and out of treatment compared to the general population. Cox models compare the hazard ratio (HR) of overdose between heroin users in treatment and out of treatment. RESULTS: There were 41 overdose deaths, 10 during treatment and 31 out of treatment, generating annual mortality rates of 0.1% and 1.1% and SMRs of 3.9 [95% confidence interval (CI) 2.8-5.4] and 21.4 (16.7-27.4), respectively. Retention in any treatment was protective against overdose mortality (HR 0.09 95% CI 0.04-0.19) compared to the risk of mortality out of treatment, independent of treatment type and potential confounders. The risk of a fatal overdose was 2.3% in the month immediately after treatment and 0.77% in the subsequent period; compared to the risk of overdose during treatment the HR was 26.6 (95% CI 11.6-61.1) in the month immediately following treatment and 7.3 (3.3-16.2) in the subsequent period. CONCLUSIONS: We demonstrate that a range of treatments for heroin dependence reduces overdose mortality risk. However, the considerable excess mortality risk in the month following treatment indicates the need for greater health education of drug users and implementation of relapse and overdose death prevention programmes. Further investigation is needed to measure and weigh the potential benefits and harms of short-term therapies for opiate use.

Changing pattern of drug abuse among patients entering treatment in Lazio, Italy, between 1996 and 2003: transition from heroin to cocaine use.

AIM: This study describes temporal changes of the pattern of substance abuse among drug users in treatment in Lazio, Italy. METHODS: We used individual data from the surveillance system of drug users of the Lazio region. We measured temporal changes in: the number of drug users in treatment, main and any substance of abuse, and mode of referral to treatment. RESULTS: Among new clients, the proportion of heroin use decreased from 78.2% in 1996 to 37.6% in 2003 (p < 0.0001), while cocaine use increased from 4.1% in 1996 to 30.1% in 2003 (p < 0.0001). In 2003, any use of cocaine was reported by 43.1% of new cases as compared to 38.9% taking heroin, 36.8% cannabis and 5.3% other substances, 41.9% using more than one substance. In 2003, 37.7% of new patients were referred to treatment by the police as compared to 10.4% in 1996. CONCLUSIONS: Heroin use has been replaced by cocaine among people coming to treatment centres for the first time. The main mode of access to treatment of new cocaine and cannabis users occurred through mandatory referral by the police. Routine surveillance systems of treatment demand are essential to monitor temporal trends of patterns of drug use in order to plan proper treatment strategies.

[Mortality of drug users attending public treatment centers in Italy 1998-2001: a cohort study]. / Mortalità in una coorte di tossicodipendenti da eroina arruolati presso i Ser.T in Italia, 1998-2001.

OBJECTIVES: to describe the overall and cause-specific mortality among heroin users attending Public Treatment Centers (PTCs) in Italy and to estimate the impact of heroin use on mortality in the general population. SETTING AND PARTICIPANTS: A cohort of 10,376 patients (8881 men and 1495 women) enrolled over a period of 18 months between september 1998 and september 2000 and followed-up through 31st of March 2001 (VEdeTTE study). RESULTS: 190 deaths occurred during the study period (153 men and 37 women): 70 deaths were due to overdose (36.8%), 38 to AIDS (20.0%), 30 to violence (15.8%). The direct standardized overall mortality rate per 1000 person/years is 12.0 (CI 95% 5.4-18.6): 12.7/1000 p-y (CI 95% 4.9-20.5) among males and 8.4/1000 p-y (95% CI 4.7-12.2) among females. This study confirms that overdose is the leading cause of death in heroin users (mortality rate 2.6/1000 p-y (95% CI 0.8-4.5) among males and 4.0/1000 p-y (95% CI 0.9-7.2) among females. AIDS mortality rates are 2.6/1000 p-y, 95% CI 0.6-4.6 among males and 1.8/1000 p-y (95% CI 0.4-3.1) among females. The mortality rate for all the other causes is 6.0/1000 p-y (95% CI 0.0-14.0) among males and 2.3/1000 p-y (95% CI 0.9-3.6) among females. The standardized mortality ratios for all causes in comparison to age and gender matched general population show the excess particularly important for females (SMR 6.7; 95% CI 5.7-7.8 for males and SMR 22.8; 95% CI 16.5-31.5 for females). The population attributable fraction highlights that 14.4% (95% IC 10.9-18.5) of deaths in people aged 30-34 in Italy in 2000 could be attributed to heroin addiction; the fraction decreases to 10.7% (95% CI 6.9-15.6) at age 25-29 and to 12.8% (95% CI 9.9-16.2) at age 35-39. CONCLUSIONS: Mortality observed in this cohort is lower than that observed in previous studies, mainly due to reduction of AIDS and overdose mortality. The excess mortality over matched population is confirmed. Study population is older than in other studies (mean age at enrollment 31.1; DS 6.2); and the observation time is mainly spent in treatment. The mortality attributable faction shows that almost the 13% of deaths around the third decade of age can be attributed to drug dependence even though it is important to take into consideration the assumptions about drug addiction prevalence in the general population.

[Characteristics and effectiveness of smoking cessation programs in Italy. Results of a multicentric longitudinal study]. / Interventi per la cessazione dell'abitudine al fumo in Italia: offerta ed efficacia nella pratica. Risultati di uno studio longitudinale multicentrico.

AIM: to describe the characteristics and effectiveness of various smoking cessation programs offered by Italian treatment services operating within the National Health Service. DESIGN: prospective longitudinal multicentre study involving 41 smoking cessation services in 16 Italian regions. STUDY POPULATION: the study population includes patients entering smoking cessation programs between April 2003 and June 2004. The "study population" includes 1226 patients (54.2% males and 45.4% females), mean age 47 years. Patients have a middle/high level of education and a long history of smoking; most are highly dependent on nicotine and report previous attempts to quit smoking. METHODS: treatment effectiveness in smoking cessation is assessed six months after entering treatment service. Logistic Regression Model was used to determine the predictors of successfiul cessation, independent of treatment typology. The predictors were included as confounding variables in the logistic regression model that was used to evaluate the effectiveness of treatments. Besides the effect of treatment completion on smoking cessation was estimated. RESULTS: predictors of successful smoking cessation are: being male, presence of a partner, strong motivation to quit, previous attempts to give up smoking, mild nicotine dependence, and not suffering from mood disturbances. All treatments are effective in helping people to stop smoking: cessation rate ranges between 25.00% for patients receiving a single session of motivational counselling and 65.3% for those receiving nicotine replacement therapy combined to group therapy. Compared to a single session of motivational counseling, nicotine replacement therapy combined to group therapy is the most effective therapeutic program (OR 5.4; 95%CI 12.5-12.0). Treatment completion is a strong determinant ofsuccess (OR 4.8; 95%CI 3.5-6.4). CONCLUSION: enrolling people in any type of therapeutic program, in particular nicotine replacement therapy combined with group therapy increases the probability of successfully quitting smoking; moreover, patients that begin a smoking cessation program should be encouraged to complete the therapy