[The care pathway of patients with diffuse large B-cell lymphoma described through Italian administrative healthcare data.] / Il percorso di cura dei pazienti con linfoma diffuso a grandi cellule B descritto attraverso i dati amministrativi.

INTRODUCTION: The diffuse large B-cell lymphoma (Dlbcl) is the most common non-Hodgkin lymphoma and at highest incidence among the elderly. Despite the improved outcomes of patients treated with the first-line (1L) standard of care until the end of 2022, composed by rituximab and polychemotherapy (R-Chop), during the last 20 years, the rate of relapsed and refractory Dlbcl (rrDlbcl) remains elevated. This study has identified and analyzed patients newly diagnosed with Dlbcl and treated with 1L, from the perspective of the Italian National Health Service (Ssn). METHODS: From the administrative database of Fondazione Ricerca e Salute (ReS) including ~5.5 million inhabitants/year in Italy, adults with a new in-hospital Dlbcl diagnosis (index date) and treated with 1L in 2018, 2019, 2020 and 2021 were identified and characterized in terms of demographics and comorbidities during a period (from 4 to 8 years) preceding index date. From 1 to 4 years following index date (follow-up), overall survival (Kaplan-Meier curves), percentage distribution of patients by line of therapy including dispensation/administration of chemo-immunotherapy, hemopoietic stem cell transplantation (Hsct), and direct healthcare costs charge to the Ssn, were evaluated. RESULTS: Overall, from the ReS database, 206 patients newly diagnosed with Dlbcl and treated with 1L from 2018 to 2021 in Italy (incidence from 0.9 to 1.7 x100,000 adult inhabitants) were identified. They were mainly older (median age 68 [56; 75] years), males (56%) and affected by ≥2 comorbidities (52%), mostly cardiometabolic. During 4 years of follow-up, 56% of cases in 2018 survived. During the first follow-up year: 73%, 80%, 100% and 35% of cases in 2018, 2019, 2020 and 2021, respectively, received a 2L; 42% and 64% of cases in 2018 and 2020, respectively, received a 3L. At least one Hsct was found as a 2L among cases in 2018, 2020 and 2021. On average, each patient newly diagnosed with Dlbcl and treated with 1L from 2018 to 2021 caused a total expenditure directly charged to the Ssn ranging from € 20,000 to € 30,000 during the first follow-up year (chemo-immunotherapy accounted for 40-53%), which reduced with time in favor of other drugs and Hsct. CONCLUSIONS: This analysis confirms the high rate of rrDlbcl and the high economic impact charged to the SSN to support first the chemo-immunotherapy, then the chronic care and the absence of standardized further lines of therapy for patients with rrDlbcl.

Italian healthcare resource consumptions and direct costs of adults with atopic dermatitis before and after dupilumab treatment.

BACKGROUND: Atopic dermatitis (AD) is a heterogeneous disease, associated with comorbidities, and high healthcare consumptions and costs. This study assessed the burden before and after treatment with dupilumab in adults with severe AD from 2018 to 2020, from the perspective of the Italian National Health Service (SSN). METHODS: From Fondazione Ricerca e Salute's administrative healthcare database (~5 million inhabitants/year), adults treated with dupilumab from 09/01/2018 to 31/12/2020 (index date) and a five-year lookback were identified. Age, sex and comorbidities at baseline, concomitant drugs, overnight hospitalizations, outpatient specialist services and direct costs charged to the SSN one year before/after index date were assessed. RESULTS: Of 337 adults treated with dupilumab (5.8x100,000 adult inhabitants/2019; 8.0x100,000/2020; 55% males; mean age 43±19), 68% (228/337) had ≥12-month follow-up available. Asthma was a common comorbidity (23% patients). Rates of patients treated with nearly all concomitant AD-related therapies reduced from 12 months before to 12 months after dupilumab treatment: antibacterials (from 59% to 50%), systemic corticosteroids (55% to 29%), antihistamines (54% to 38%) and cyclosporine (52% to 7%). A similar trend was observed among patients with asthma as comorbidity. Within 12 months before/after dupilumab, patients hospitalized halved from 14% to 7%, and patients receiving outpatient specialist care reduced from 72% to 65%. Annual mean direct total costs per patient treated with dupilumab charged to the SSN, net of dupilumab cost, were €1384 and €773, before and after dupilumab dispensation, respectively. CONCLUSIONS: Before dupilumab, observed patients had higher healthcare resource consumptions and direct SSN costs than after dupilumab.

The Early Access and the Potential Cost Savings by the Compassionate Use of Onco-haematological Drugs: Results from the Italian Study Compass-O.

BACKGROUND: Compassionate drug use (CDU) provides early access to not yet authorised medicines and is funded by pharmaceutical companies. The observational retrospective study Compass-O monitored the CDU of onco-haematological drugs, managed by seven Italian units for cytotoxic drug preparations (Unità Farmaci Antiblastici [UFA]), between 1 January, 2016 and 31 December, 2021. OBJECTIVE: We aimed to evaluate the CDU of onco-haematological drugs managed by seven Italian UFA, between 2016 and 2021. METHODS: The seven UFA provided anonymised data concerning CDU approved in the study period. The early access and potential cost savings for the National Health System (Servizio Sanitario Nazionale [SSN]) were analysed for CDU concerning drug-therapeutic indication combinations with complete data and reimbursed by SSN up to December 2023 (date of study execution), according to the executive decision of the Italian Medicines Agency (Agenzia Italiana del Farmaco [AIFA]). Both analyses distinguished solid/liquid tumours and categorised the combinations as innovative (fully/conditionally) or non-innovative based on AIFA assessments. RESULTS: Compass-O collected 783 CDU authorisations, with 572 (73.1%) analysable in terms of early access and cost savings. On average, early access amounted to 514 days and the total cost savings was €376,115,801. Compassionate drug use approvals involved mainly solid tumours (93.7% vs 6.3% for liquid tumours), and the combination of trastuzumab emtansine-breast cancer was the most dispensed (n = 73; early access = 426 days; potential cost savings: €610,388). Out of 572 CDU approvals, 200 (35%) were innovative drug-therapeutic indication combinations, with 598 days of early access and a total potential saving of €113,124,069. CONCLUSIONS: The study Compass-O showed a significant economic burden of CDU and a relevant need for early access, particularly for innovative drugs. However, there is currently no structured monitoring of CDU in Italy, suggesting the need for a national observatory, of which Compass-O can be the pilot phase.

Chronic Kidney Disease Eligible for SGLT2 Inhibitors Through the Integration of Italian Administrative and Primary Care Data.

Background. Patients with chronic kidney disease (CKD) can be successfully treated with sodium-glucose cotransporter-2 inhibitors (SGLT2-Is), regardless of diabetes. Fondazione Ricerca e Salute's (ReSD) administrative and Health Search's (HSD) primary care databases were combined in the Database Consortium ReS-HS to quantify and describe patients with CKD potentially eligible for SGLT2-Is and assess costs charged to the Italian National Health Service (SSN). Methods. Patients aged ≥18 with CKD and estimated glomerular filtration rate (eGFR) <60 ml/min in 2018, without dialysis and/or renal transplantation, were included. HSD was used to develop and validate algorithms for estimating eGFR, based on covariates, within the ReSD. Comorbidities, dispensed drugs, and direct healthcare costs were assessed. Results. In 2018, 66,297 (5.0% of HSD population) and 211,494 (4.4% of ReSD population) patients with CKD potentially eligible for SGLT2-Is were identified (females ≥58%). Prevalence increased with age with a peak at 75-84 years. Within HSD and ReSD cohorts, respectively: 31.0% and 41.5% had diabetes; in the observation periods, >82% and >96% received ≥1 pharmacological treatment, of which ≥50% and ≥25% received cardiovascular/blood agents and antidiabetics, respectively. From ReSD, mean per capita direct SSN cost was € 3,825 (CI 95%, € 3,655-€ 4,000): 50.1% due to hospitalizations, and 40.2% to pharmaceuticals (31.6% to cardiovascular drugs and 10.1% to antidiabetics). Conclusion. The Database Consortium ReS-HS methodology found 5% of adult SSN beneficiaries with CKD potentially eligible for SGLT2-Is bringing with them a high cardio-metabolic burden which increases the risk of CKD progression.

[Update of the Pdta Net Observatory of the ReS Foundation with all regional Care Pathways approved until 2023.] / Aggiornato l'Osservatorio Pdta Net di Fondazione ReS con tutti i Pdta regionali approvati fino al 2023.

Pdta Net, established and managed by Research and Health Foundation (ReS), is a database aimed at gathering and analysing the Regional Care Pathways (CPs) approved in Italy. A comprehensive search was conducted within institutional websites to retrieve all CPs approved by Italian Regions and Autonomous Provinces until December 2023, by utilizing specific keywords. Compared to the previous year, 51 new approvals were recorded. By now, Pdta Net collects 856 CPs, of which 476 are for high-impact chronic diseases and 380 for rare diseases.

Cardiovascular events after exacerbations of chronic obstructive pulmonary disease: Results from the EXAcerbations of COPD and their OutcomeS in CardioVascular diseases study in Italy.

INTRODUCTION: Exacerbations of chronic obstructive pulmonary disease (COPD) can increase the risk of severe cardiovascular events. OBJECTIVE: Assess the crude incidence rates (IR) of cardiovascular events and the impact of exacerbations on the risk of cardiovascular events within different time periods following an exacerbation. METHODS: COPD patients aged ≥45 years between 01/01/2015 and 12/31/2018 were identified from the Fondazione Ricerca e Salute administrative database. IRs of severe non-fatal and fatal cardiovascular events were obtained for post-exacerbation time periods (1-7, 8-14, 15-30, 31-180, 181-365 days). Time-dependent Cox proportional hazard models compared cardiovascular risks between periods with and without exacerbations. RESULTS: Of 216,864 COPD patients, >55 % were male, mean age was 74 years, frequent comorbidities were cardiovascular, metabolic and psychiatric. During an average 34-month follow-up, 69,620 (32 %) patients had ≥1 exacerbation and 46,214 (21 %) experienced ≥1 cardiovascular event. During follow-up, 55,470 patients died; 4,661 were in-hospital cardiovascular-related deaths. Among 10,269 patients experiencing cardiovascular events within 365 days post-exacerbation, the IR was 15.8 per 100 person-years (95 %CI 15.5-16.1). Estimated hazard ratios (HR) for the cardiovascular event risk associated with periods post-exacerbation were highest within 7 days (HR: 34.3, 95 %CI: 33.1-35.6), especially for heart failure (HR 50.6; 95 %CI 48.6-52.7) and remained elevated throughout 365 days (HR 1.1, 95 %CI 1.02-1.13). CONCLUSIONS: COPD patients in Italy are at high risk of severe cardiovascular events following exacerbations, suggesting the need to prevent exacerbations and possible subsequent cardiovascular events through early interventions and treatment optimization.

[The domino effect of drug distribution channels on the management of chronicity.] / L'effetto domino dei canali distributivi dei farmaci sulla gestione della cronicità.

Drug distribution channels affect all actors in the drug supply chain: healthcare institutions, healthcare professionals, patients, pharmacies, pharmaceutical companies and distributors. They should be redesigned in line with the new proximity care model planned in the Pnrr and DM 77, while avoiding a negative domino effect on the management of chronic diseases. A guide recently published by the MaCroScopio project is useful to shed light on this issue and to understand the relationship between the distribution channels present in Italy (distribuzione diretta - DD; distribuzione per conto - Dpc; distribuzione convenzionata) and the management of chronic diseases. Analysis of OsMed data showed that the majority of medicines dispensed in DD and Dpc are for chronic patients; therefore, a change in distribution channels inevitably affects chronicity management and could lead to increased expenditure. It is necessary to evaluate the transfer of drugs from one channel to another on a case-by-case basis according to the specifics of each drug. Proximity care reform requires a redesign of drug distribution channels, but this must be done with respect to the clinical, social and economic sustainability of the system.

Primary Sjögren's syndrome in Italy: Real-world evidence of a rare disease through administrative healthcare data.

OBJECTIVES: Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease with significant impact on morbidity, mortality, and quality of life. This study aimed to evaluate epidemiology, healthcare needs and related costs of pSS patients from the Italian National Health Service perspective. METHODS: From the Fondazione Ricerca e Salute's database (∼5 million inhabitants/year), pSS prevalence in 2018 was calculated. Demographics, mean healthcare consumptions and direct costs at one year following index date (first in-hospital diagnosis/disease waiver claim) were analysed through an individual direct matched pair case-control analysis (age, sex, residency). RESULTS: In Italy, 3.8/10,000 inhabitants were identified as affected by pSS (1,746 case: 1,746 controls) in 2018. In the year following index date, 53.7% of cases and 42.7% of controls received ≥1 drug (p<0.001); mean per capita cost was €501 and €161, respectively (p<0.01). At least one hospitalization occurred to 7.8% of cases and 3.9% of controls (p<0.001) with mean per capita costs of €416 and €129, respectively (p = 0.46). At least one outpatient specialist service was performed in 49.8% of cases and 30.6% of controls (p<0.001); mean per capita costs were €200 and €75, respectively (p<0.01). Overall, mean annual costs were €1,171 per case and €372 per control (p < 0.01). CONCLUSION: According to results of this population-based study, the prevalence of pSS in Italy appears to be consistent with the definition of rare disease. Patients with pSS have higher pharmacological, in-hospital and outpatient specialist care needs, leading to three-times higher overall cost for the INHS, compared to the general population.

Italian healthcare resource consumption for patients on hemodialysis treated for chronic kidney disease-associated pruritus (CKD-aP).

Background: Chronic kidney disease-associated pruritus (CKD-aP) affects patients on hemodialysis. This study identified hemodialysis patients presumably affected or not affected by CKD-aP and integrated healthcare costs, from the perspective of the Italian administrative healthcare data. Methods: Through cross-linkage of Italian administrative healthcare data collected between 2015 and 2017 (accrual period) in the database of Fondazione ReS (Ricerca e Salute), patients undergoing in-hospital/outpatient hemodialysis were selected. Cohorts with and without CKD-aP were created based on the presence/absence of CKD-aP-related treatment (according to common clinical practice and guidelines) supplies and assessed in terms of CKD-aP-related treatments and mean healthcare costs per capita paid by the Italian National Health Service (INHS). Results: Of 1,239 people on hemodialysis for ≥2 years, CKD-aP affected 218 patients. Patients with CKD-aP were older and with more comorbidities. During the follow-up year, on average, the INHS spent €37,065 per case, €31,286 per control and € 35,988 per non-CKD-aP subject. High-efficiency dialytic therapies performed to people on hemodialysis with CKD-aP largely weighed on the overall mean annual cost. Conclusions: This real-world study identified patients on chronic hemodialysis potentially treated for CKD-aP. Interestingly, high-efficiency dialysis seems the most frequent and expensive choice for the treatment of CKD-aP. The discovery of appropriate and effective treatments for this condition might offer cost offsets.

[The population affected by neovascular age-related macular degeneration and treated with anti-Vegf through Italian administrative healthcare data.] / La popolazione con degenerazione maculare neovascolare correlata all'età trattata con anti-Vegf attraverso i dati amministrativi sanitari.

INTRODUCTION: The neo-vascular age-related macular degeneration (nAmd) is a frequent cause of vision loss, although the intravitreal (Ivt) injections of anti-Vegf (vascular endothelial growth factor) have improved functional outcomes. This study has assessed the healthcare and economic burden on the Italian national health service (Inhs) for patients with nAmd and new users of anti-Vegf. METHODS: From the database of Fondazione Ricerca e Salute (ReS), people aged ≥55 and with an in-hospital diagnosis of nAmd and/or an injection of anti-Vegf (aflibercept, ranibizumab, pegaptanib; index date) in 2018 are selected. Those with other conditions treated with anti-Vegf and with an Ivt injection before 2018 are excluded. New users of anti-Vegf are analyzed by sex, age, comorbidities, Ivt administrations, switch of anti-Vegf, local outpatient specialist services (with some focuses) and direct healthcare costs charged to the Inhs Results. In 2018, of 8125 inhabitants aged ≥55 with nAmd (4.6x1000 inhab.; mean age 76±9; F: 50%), 1513 (19%) are new users of Ivt anti-Vegf (mean age 74±9), whose incidence (0.9x1000) increased with age until 84 years old. A proportion of 60.7% had ≥2 comorbidities (mainly hypertension, dyslipidemia and diabetes). Within the 2nd follow-up year, only 598 patients are still treated (60% were lost). On average, 4.8 Ivt injections in the first and 3.1 in the second year are registered. On average, the total cost charged to the Inhs per new user of anti-Vegf was € 6726 (Ivt anti-Vegf accounted for the 76%) and € 3282 (hospitalizations for causes different from nAmd accounted for the 47%), during the first and the second year, respectively. CONCLUSIONS: This analysis suggests that in Italy people with nAmd and new users of anti-Vegf are elderly, affected by many comorbidities, treated with Ivt anti-VEGF less than what is required and authorized to achieve a benefit, undergo very few follow-up outpatient specialist visits and tests and, within the 2nd year, their hospitalizations for causes different from nAmd mainly weighs on the total expenditure charged to the Inhs.

A methodology to assess the population size and estimate the needed resources for new licensed medications by combining clinical and administrative databases: The example of glycated haemoglobin in type 2 diabetes.

PURPOSE: To develop and validate a model to estimate glycated haemoglobin (HbA1c) values in patients with type 2 diabetes mellitus (T2DM) using a clinical data source, with the aim to apply this equation to administrative databases. METHODS: Using a primary care and administrative Italian databases, namely the Health Search database (HSD) and the ReS (Ricerca e Salute) database, we selected all patients aged 18 years or older on 31 December 2018 being diagnosed with T2DM and without prior prescription of sodium-glucose cotransporter-2 (SGLT-2) inhibitors. We included patients prescribed with and adherent to metformin. HSD was used to develop and test (using 2019 data as well) the algorithm imputing HbA1c values ≥7% according to a series of covariates. The algorithm was gathered by combining beta-coefficients being estimated by logistic regression models using complete case (excluding missing values) and imputed (after multiple imputation) dataset. The final algorithm was applied to ReS database using the same covariates. RESULTS: The tested algorithms were able to explain 17%-18% variation in assessing HbA1c values. Good discrimination (70%) and calibration were obtained as well. The best algorithm (three) cut-offs, namely those providing correct classifications ranging 66%-70% was therefore calculated and applied to ReS database. By doing so, from 52 999 (27.9, 95% CI: 27.7%-28.1%) to 74 250 (40.1%, 95% CI: 38.9%-39.3%) patients were estimated with HbA1c ≥7%. CONCLUSION: Through this methodology, healthcare authorities should be able to quantify the population eligible to a new licensed medication, such as SGLT-2 inhibitors, and to simulate scenarios to assess reimbursement criteria according to precise estimates.

Do more targets allow more cancer treatments, or not?

The three current oncology models (histological, agnostic and mutational) mainly differ in clinical, technological and organisational aspects, leading to different regulatory procedures and implications in antineoplastic therapy access by patients. Within the histological and agnostic models, Regulatory Agencies authorise target therapies and define their price, reimbursement, prescription and access based on results from clinical trials including patients affected by the same tumour (histological) or subjects with specific genetic mutations regardless of the tumour site or the histology (agnostic). The mutational model has been developed to identify specific actionable molecular alterations found by next-generation sequencing test-based large platforms on solid and liquid biopsies. Nevertheless, due to the highly uncertain efficacy and possible toxicity of drugs tested within this model, regulatory procedures based on histological or agnostic oncology cannot be followed. Multidisciplinary skills are required (e.g. the molecular tumour board's (MTB) representatives) to identify the best association between the genomic profile and the drug planned to be used, but quality requirements, practices and procedures of these discussions still need to be standardised. Real-world evidence from clinical practice (i.e. genomic findings, clinical data and MTBs' choices) lacks, therefore, it is urgently needed as opposed to limited findings from clinical trials. A potential solution for an appropriate access to the therapy chosen by the mutational model can be the indication-value-based sub iudice procedure of authorisation. The access to therapies suggested by extensive molecular profiling could be easily implementable within the Italian national health system, thanks to the existing regulatory procedures, i.e. the managed-entry agreements and the antineoplastic drug monitoring registries, alongside those granted by conventional studies (phase I, II, III, IV) conducted according to the histological and agnostic models.

Acute myeloid leukemia: Incidence, transplantation and survival through Italian administrative healthcare data.

OBJECTIVE: To identify newly diagnosed patients with acute myeloid leukemia in 2017 treated with intensive chemotherapy or unfit for intensive chemotherapy, and to assess their probability of receiving allogeneic stem cell transplantation and survival, from the Italian National Health Service perspective. PATIENTS AND METHODS: From the Ricerca e Salute database, adults with an in-hospital diagnosis of acute myeloid leukemia (International Classification of Disease-9th version-Clinical Modification code 205.0x) in 2017 (index date), without any identifying acute myeloid leukemia criteria within the preceding year, were selected. Among them, subjects treated with intensive chemotherapy (chemotherapy during an overnight hospitalization) within one year after index date were identified. The remaining were considered unfit for intensive chemotherapy. Gender, age and comorbidities were described. Within the follow-up period, probabilities of in-hospital allogeneic stem cell transplantation and overall survival were assessed through Kaplan Meier analyses. RESULTS: From 4,840,063 beneficiaries of the Italian National Health Service, 368 newly acute myeloid leukemia diagnosed adults (9.0 *100,000) were selected. Males comprised 57%. Mean age was 68±15. There were 197 patients treated with intensive chemotherapy. The remaining 171 unfit for intensive chemotherapy were older (72±14) and with more comorbidities (e.g. hypertension, chronic lung diseases and chronic kidney disease). Only patients treated with intensive chemotherapy underwent an allogeneic stem cell transplantation (41; 33%) during the one year after the index date. Within the first and second follow-up year, respectively: 41.1% and 26.9% of subjects treated with intensive chemotherapy (144) survived (median survival time: 7.8 months); 25.7% and 18.7% of those unfit for intensive chemotherapy (139) survived (1.2 months). Difference was significant (p<0.0001). Within one and two years after transplantation (41 patients), 73.5% and 67.3% of subjects survived, respectively. CONCLUSION: This study, by showing the incidence of acute myeloid leukemia in Italy in 2017, the proportion of patients treated with intensive chemotherapy from the new diagnosis, the use of allogeneic stem cell transplantation and two-year survival, integrated evidence on large and unselected populations and may help to improve treatment strategies of older acute myeloid leukemia patients.

[Community acquired pneumoniae and chronic obstructive pulmonary disease: the RWE analysis of events that required hospitalizations, and healthcare integrated costs.] / Polmonite acquisita in comunità e broncopneumopatia cronica-ostruttiva: analisi RWE degli eventi che hanno richiesto il ricovero ospedaliero e dei costi assistenziali associati.

INTRODUCTION: The community-acquired pneumonia (Cap) and the acute exacerbation of chronic obstructive pulmonary disease (Aecopd) frequently receive wrong therapies, leading to the increase of healthcare consumption resources, direct and indirect costs, and antimicrobial resistance. This study identified Cap and Aecopd hospitalized events, and analyzed them in terms of comorbidities, antibiotic use, re-hospitalizations, diagnostics and costs, from the perspective of the Italian national health service (Inhs). METHODS: From the database of Fondazione Ricerca e Salute (ReS), hospitalizations for Cap and Aecopd from 2016 to 2019. Demographics, comorbidities and mean in-hospital stay at the baseline, antibiotics reimbursed by the Inhs within 15 days before and after the index event, outpatient diagnostics performed before the event and in-hospital diagnostics, and direct costs charged to the Inhs, are assessed. RESULTS: From 2016 to 2019 (~5 million inhabitants/year), 31,355 events of Cap (1.7x1000/year) and 42,489 events of Aecopd (4.3x1000 inhabitants aged ≥45/year) were identified, of which 32% and 26.5%, respectively, were treated with antibiotics before the hospitalization. The highest frequency of hospitalizations and comorbidities, and the longest mean in-hospital stays are found among elderly. Events not treated before and after the hospitalization showed the longest in-hospital stay. More than 12 Ddd (defined daily dose) are dispensed after the discharge. Local outpatient diagnostics are performed before the admission to <1% of the events; in-hospital diagnostics are registered in 5.6% and 1.2% of Cap and Aecopd, respectively, discharge forms. About 8% and 24% of Cap and Aecopd, respectively, are re-hospitalized during one subsequent year, mainly within one month. The mean expenditures per event of Cap and Aecopd were € 3646 and € 4424, respectively: hospitalizations, antibiotics and diagnostics accounted for the 99%, 1% and <0.1% of the total expense, respectively. CONCLUSIONS: This study provided a very high dispensation of antibiotics after the hospitalization for Cap and Aecopd, while a very low use of differential diagnostics available within the observed periods, to the detriment of the enforcement actions proposed at institutional levels.

Variables associated with joint involvement and development of a prediction rule for arthritis in patients with psoriasis. An analysis of the Italian PsoReal database.

BACKGROUND: Limited data exist to predict the development of psoriatic arthritis (PsA) in patients with psoriasis (PsO). OBJECTIVE: To analyze factors associated with incident PsA in patients with PsO, and to develop a predictive algorithm for progression to arthritis using a full set of variables and a restricted one applicable to administrative data. METHODS: Cohort study within the PsoReal registry in Italy. Multivariable generalized linear models were used to assess factors associated with PsA and to derive a predictive model. RESULTS: Among 8895 patients, 226 PsA cases were identified (incidence 1.9 per 100 patient-years). Independent predictors in the full model were as follows: female sex, age 40 to 59 years, body mass index ≥ 25, chronic-plaque PsO features, presence of palmoplantar pustulosis, hospitalization for PsO in the last 5 years, and previous use of systemic PsO therapy (area under the receiver operating characteristic curve = 0.74). Female sex, age 40 to 59 years, hospitalization for PsO, and previous use of systemic PsO therapy were independent predictors in the restricted model (area under the receiver operating characteristic curve = 0.72). LIMITATIONS: Lack of other potential predictors for PsA. CONCLUSION: Our models could be used by clinicians and health authorities when planning intervention and population surveillance. Future studies should confirm our models using larger datasets and additional variables.

[Occurrence of cardiovascular events within a large population of patients affected by rheumatoid arthritis with or without diabetes.] / Sviluppo di eventi cardiovascolari in un'ampia popolazione di pazienti affetti da artrite reumatoide con o senza diabete.

INTRODUCTION: Rheumatoid arthritis (Ra) and diabetes are often associated with chronic multimorbidity and share the high risk of development of major cardiovascular events (Mace). This study aimed to identify and analyse patients with only Ra, Ra + diabetes, and only diabetes, in terms of comorbidities and new occurrence of Cv events, from the perspective of the Italian national health service (Inhs). METHODS: Starting from the Fondazione ricerca e salute (ReS)'s database, through the record linkage of administrative healthcare data, cohorts with only Ra, Ra + diabetes and only diabetes have been selected, characterized (age and sex), and analysed by comorbidity (depression, dyslipidemia, hypertension, hemorrhagic stroke and ischemic stroke/transient ischemic attack - Tia, coronary artery disease - Cad, heart failure - Hf, chronic liver disease, periphery artery disease - Pad, chronic kidney disease, asthma/chronic obstructive pulmonary disease - Copd, neoplasia) and by new Cv events (Hf, Cad and ischemic stroke/Tia) within two follow-up years (Kaplan-Meier curves). A logistic regression model defined contribution and type of association of some variables on new Cv events. RESULTS: In 2018, from 5.375.531 Inhs beneficiaries in the ReS database, 13.698 (0.25%) were affected by only Ra, 1728 (0.03%) by Ra + diabetes, 347,659 (6.8%) by only diabetes. The only Ra cohort was composed by more females, younger and with less comorbidities patients. Proportions of 79.3%, 70.8% and 38.5% of patients with Ra + diabetes, only diabetes and only Ra were affected by 2 to ≥4 comorbidities: among patients with Ra + diabetes, comorbidities showed the highest frequencies, mainly hypertension, dyslipidemia and asthma/Copd. Within two follow-up years, about 8% of patients with diabetes with/without Ra developed a new Cv event (vs 3% with only Ra). The presence of Ra/diabetes or Ra + diabetes, male sex, older age and comorbidities of interest resulted significantly (p<0.01) associated with a higher Cv risk. CONCLUSIONS: Comorbidities and the co-presence of diabetes in patients with Ra determine a complicated framework with high risk of Cv events. It is worthy include more complex patients in clinical trials, in order to generate evidence useful for even more multidisciplinary medical teams.

How many and who are patients with heart failure eligible to SGLT2 inhibitors? Responses from the combination of administrative healthcare and primary care databases.

BACKGROUND: Recent successful findings (i.e. DAPA-HF trial) in patients with heart failure (HF) with/without diabetes treated with sodium-glucose co-transporter inhibitors (SGLT2-I) have fostered real-world data analyses. Fondazione Ricerca e Salute's (ReSD) administrative and Health Search's (HSD) primary healthcare databases were combined in the ReS-HS DB Consortium, to identify and characterize HF-patients eligible to SGLT2-I, and assess their costs charged to the Italian National Health Service (INHS). METHODS AND RESULTS: Eligibility to SGLT2-I was HF diagnosis, age ≥ 18 years, reduced (≤40%) ejection fraction (HFrEF) and glomerular filtration rate (GFR) ≥30 ml/min. The HSD, including 13,313 HF-patients (1.5% of the total HSD population) was used to develop and test the algorithms for imputing HFrEF and GFR ≥ 30 ml/min, based on a set of covariates, to the ReSD, including 67,369 (1.5% of the total ReSD population). Subjects eligible to SGLT2-I were 2187 in HSD (61.1% of HFrEF); after the imputation, 15,145 in ReSD (58.8% of HFrEF). Prevalence of eligibility to SGLT2-I was higher in males then in females and increased with age; diabetic patients were 44.3% and 33.4% of HSD and ReSD populations eligible to SGLT2-I, respectively. Estimated from ReSD, the mean annual cost charged to the INHS per patient with HF eligible to SGLT2-I was €7122 (68% due to hospitalizations). CONCLUSIONS: Approximately 20% of patients with HF was eligible to SGLT2-I. Real-world data can identify, quantify and characterize patients eligible to SGLT2-Is and assess related costs for the health care system, thus providing useful information to Regulatory Decision makers.

[A view of care pathways approved by Italian Regions, to face the challenge of the community-based healthcare: a quali-quantitative analysis of the Pdta Net database.] / Conoscere i percorsi diagnostico-terapeutici assistenziali (Pdta) regionali approvati in Italia per affrontare il cambiamento della assistenza di prossimità: analisi quali-quantitativa del database Pdta Net.

INTRODUCTION: The adoption of a Care Pathway (CP) allows the healthcare management of patients suffering from high-epidemiological impact chronic diseases. The continuity of care of these patients is one of the main purposes of the community-based healthcare reform, foreseen in the 6th Mission of the National recovery and resilience plan. Fondazio-ne Ricerca e Salute (ReS) collects and analyses regional CPs approved in Italy, through the Pdta Net database. METHODS: Fondazione ReS has retrieved all the CPs approved by Italian Regions and Autonomous provinces until 12/31/2021 within institutional websites, through specific keywords. The quali- and quantitative analysis of CPs was based on the approving Region, the publication year, the disease (distinguishing between high-epidemiological impact chronic diseases and rare conditions) and clinical area. Following the 5-year experience gained by Fondazione ReS in terms of CPs' aims and organization for the full realization of an evidence-based healthcare of chronic patients, all data collected until 12/31/2021 underwent an in-depth double-blinded quality control. This control was aimed to make the Pdta Net database as representative as possible of the existing documents closest to a real CP. RESULTS: From 2005 to 2021, 729 regional CPs have been approved: 404 on high-impact chronic diseases and 220 on rare conditions. The CPs of chronic diseases, mostly edited by Piemonte (45 CPs), Campania (34) and Toscana (33) Regions, mainly concern on diabetes (19), chronic obstructive pulmonary disease (15), heart failure (13), stroke, multiple sclerosis and colorectal neoplasms (12 each one), breast cancer (11), dementia and chronic kidney disease (10 each one). Most of the CPs on rare diseases have been edited by Regions with an established Rare Disease Network, i.e., Lombardia (125 CPs), Lazio (74) and Toscana (40): neurology (61) and oncology (52) were the most represented clinical areas. CONCLUSIONS: The high number of CPs approved in Italy confirms an increasing interest of the healthcare institutions. The collected CPs show an extreme variety of titles, text structures and disease choices. Given the absence of an institutional observatory and of devotees of shared and harmonized CPs, annually Pdta Net makes available an updated and complete overview of these governance tools, which are essential for the upcoming changes of the Italian national health service.