Surgical Treatment of Active Endocarditis Pre- and Post-COVID-19 Pandemic Onset.

BACKGROUND: Despite advanced diagnosis and treatment, infective endocarditis (IE) is a potentially life-threatening condition. The impact of COVID-19 on the diagnosis and outcome of the surgical treatment of IE is uncertain. The aim of this study was to analyze the incidence, characteristics, and outcomes of surgically treated IE before and after the COVID-19 pandemic. METHODS: This study retrospectively analyzed the data of 535 patients who underwent valve surgical procedures for IE between January 2010 and December 2022 in a single cardiac surgery center. Patients were divided into two groups depending on the date of their operation: before (n = 393) and after (n = 142) COVID-19 onset. In order to balance the groups, inverse probability of treatment weighting (IPTW) calculated from the propensity score (PS) was applied. Weighted univariate logistic regressions were reported for outcomes; weights were derived from IPTW. Interrupted time series analysis (ITSA) according to Linden's method was used to evaluate the changes in the manifestation of IE after 11 March 2020. RESULTS: Patients from the post-COVID-19 cohort (after 11 March 2020) had a greater number of comorbidities such as diabetes (29.6% vs. 16.3% p = 0.001), hypertension (71.1% vs. 59.5% p = 0.015), and preoperative kidney injury requiring dialysis (9.2% vs. 2.5% p = 0.002), but the median additive and logistic EuroSCORE were not statistically different. In the post-COVID-19 group, we observed a greater prevalence of Staphylococcus aureus-related endocarditis (24.5% vs. 15.4% p = 0.026), a consequent reduction in Staphylococcus non aureus-related endocarditis (12.2% vs. 20.1% p = 0.048), and a decrease in aortic valve replacements (43.0% vs. 53.9%), while the number of mitral valve replacements and repair was greater (21.1% vs. 15.0% and 6.3% vs. 4.3%, respectively). No differences were found in the two groups concerning early death, death, or relapse at 1 year after surgery. Data obtained by multivariable analysis identified preoperative renal dysfunction requiring dialysis as the only common risk factor for early mortality via stratifying by time periods in analysis. CONCLUSIONS: The incidence of surgically treated IE significantly increases after the COVID-19 pandemic with a higher incidence of mitral valve involvement with respect to the aortic valve. Although a delay in surgical timing occurred during the COVID-19 pandemic, data in terms of mortality and outcomes were largely unaffected.

Estimation of patients affected by inflammatory bowel disease potentially eligible for biological treatment in a real-world setting.

BACKGROUND/AIMS: This analysis estimated the number of inflammatory bowel disease (IBD) patients presenting criteria of eligibility for biological therapies in an Italian real-world setting. METHODS: An observational analysis was performed on administrative databases of a sample of Local Health Units, covering 11.3% of the national population. Adult IBD patients (CD or UC) from 2010 to the end of data availability were included. Eligibility criteria for biologics were the following: Criterion A, steroid-refractory active disease; Criterion B, steroid-dependent patients; Criterion C, intolerance or contraindication to conventional therapies; Criterion D, severe relapsing disease; Criterion E (CD only), highly active CD disease and poor prognosis. RESULTS: Of 26,781 IBD patient identified, 18,264 (68.2%) were treated: 3,125 (11.7%) with biologics and 15,139 (56.5%) non-biotreated. Among non-biotreated, 7,651 (28.6%) met at least one eligibility criterion for biologics, with criterion B (steroid-dependence) and criterion D (relapse) as the most represented (58-27% and 56-76%, respectively). Data reportioned to the Italian population estimated 67,635 patients as potentially eligible for biologics. CONCLUSIONS: This real-world analysis showed a trend towards undertreatment with biologics in IBD patients with 28.6% being potentially eligible, suggesting that an unmet medical need still exists among the Italian general clinical practice for IBD management.

Post-Operative Delirium and Cognitive Dysfunction in Aged Patients Undergoing Cardiac Surgery: A Randomized Comparison between Two Blood Oxygenators.

In elderly patients undergoing cardiac surgery, extracorporeal circulation affects the incidence of post-operative delirium and cognitive impairment with an impact on quality of life and mortality. In this study, a new oxygenator system (RemoweLL 2) was tested against a conventional system to assess its efficacy in reducing the onset of postoperative delirium and cognitive dysfunction and the levels of serum inflammatory markers. A total of 154 patients (>65 y.o.) undergoing cardiopulmonary bypass (CPB) were enrolled and randomly assigned to oxygenator RemoweLL 2 (n = 81) or to gold standard device Inspire (n = 73) between September 2019 and March 2022. The aims of the study were to assess the incidence of delirium and the cognitive decline by neuropsychiatric tests and the MoCa test intra-hospital and at 6 months after CPB. Inflammation biomarkers in both groups were also evaluated. Before the CPB, the experimental groups were comparable for all variables. After CPB, the incidence of severe post-operative delirium showed a better trend (p = 0.093) in patients assigned to RemoweLL 2 (16.0%) versus Inspire (26.0%). Differences in enolase levels (p = 0.049), white blood cells (p = 0.006), and neutrophils (p = 0.003) in favor of RemoweLL 2 were also found. The use of novel and better construction technologies in CPB oxygenator devices results in measurable better neurocognitive and neurological outcomes in the elderly population undergoing CPB.

Less Is More? Combined Approaches to Improve Mortality and Morbidity after Aortic Valve Replacement.

BACKGROUND: Nowadays, one of the main goals of aortic valve surgery is to reduce the biological impact, mortality, and complications. It is well-known that long operative times in terms of the extracorporeal circulation, but above all, of the aortic cross-clamp time (ACC), represent a risk factor for mortality in patients undergoing cardiac surgery. In order to shorten the aortic cross-clamp time, many technological improvements, such as sutureless prostheses, have been introduced, but their actual effectiveness has not been proven yet. The aim of this study was to assess the 30-day outcomes of patients undergoing aortic valve replacement surgery, focusing on the ACC length. METHODS: All 3139 patients undergoing aortic valve replacement between January 2013 and July 2022 at our institution were enrolled. The data were retrospectively collected and the baseline characteristics and intraoperative variables were recorded. In order to adjust the results according to the differences in the baseline characteristics, propensity score matching was performed and four groups of 351 patients were obtained based on the first, second, third, and fourth quartile of the ACC time. RESULTS: The patient population included 132 redo surgeries (9.4%) and 61 cases of active endocarditis (4.3%), with an overall median EuroSCORE II of 1.8 (IQR 1.2-3.1). An increase across the groups was observed in terms of the acute kidney failure (p < 0.001) incidence, the number of blood transfusions (p = 0.022), prolonged hospital stays (p < 0.001), the and respiratory failure (p < 0.001) incidence. A p of < 0.1 was found for the 30-day mortality (p = 0.079). The predictors of an early 30-day mortality were standard full sternotomy (OR 2.48, 95% CI 1.14-5.40, p = 0.022), EuroSCORE II (OR 1.10, 95% CI 1.05-1.16, p < 0.001), and a trend for a longer ACC time (Q4 vs. Q1: OR 2.62, 95% CI 0.89-7.68, p = 0.080). CONCLUSIONS: Shortening the operative times resulted in marked improvements of the patients' outcomes. The combined use of minimally invasive approaches and sutureless aortic valve prostheses allows for a lower 30-day events rate. New technologies should be assessed to obtain the best results with the least risk.

Estimation of patients with psoriasis potentially eligible and currently untreated with biological drugs in Italy.

BACKGROUND: Psoriasis (PSO) patients can benefit from the growing availability of novel biological agents, that are often underused or discontinued. This real-world analysis estimated PSO patients potentially eligible and currently untreated with biologics in Italy. METHODS: An observational analysis was performed on administrative databases of a pool of healthcare entities, covering 11.3% of Italian population. During the inclusion period (2010- 2020), patients were identified by: 1) at least one prescription of topical drugs for PSO; or 2) active exemption for PSO; or 3) at least one PSO hospital discharge diagnosis. The index-date was the first PSO identification across inclusion period. Eligibility for biologics was evaluated prior to index-date (characterization period) through two not-mutually exclusive criteria: Criterion A, failure of at least one systemic treatment, and/or Criterion B, onset of psoriatic arthritis (PsA). Data were re-proportioned to the Italian population. RESULTS: The study sample showed a PSO prevalence of 2%. Projection to 2020 national population (N=59,236.213) estimated 1.43 million Italian patients affected by PSO: 95% treated with conventional therapies, 4% with biologics, and 1% untreated. Among those non-treated with biologics, 3.8% of overall PSO patients met one or both eligibility criteria for biologics, specifically 25% met criterion A (failure to conventional treatments), 68% criterion B (PsA co-diagnosis), and 7% met both. About half of them had 1 or 2 comorbidities and 30% above 3. CONCLUSIONS: These findings from real clinical practice estimated about 4% PSO patients potentially eligible for biologics, but still untreated, with nearly one-third exhibiting a complex comorbidity profile.

Description of characteristics, management of care and healthcare direct costs of patients with HR+/HER2- early breast cancer in Italy: a real-world study involving administrative and pathological anatomy databases.

BACKGROUND: Healthcare administrative and pathological anatomy data were used to identify Italian patients with early breast cancer (EBC) with HR+/HER2- status at high risk of recurrence, evaluating drug utilization and other healthcare resource use in clinical practice. METHODS: This retrospective analysis, based on 9.4 million of Italian National Health Service beneficiaries, included adult patients with hospitalization discharge diagnosis for EBC in 01/2015-12/2020. Those with HR+/HER2- status were selected; among them, patients that underwent removal of lymph nodes (LN) were analyzed. RESULTS: Of 24,137 patients with EBC and HR+/HER2- status, 3619 patients (15%) had documented LN removal. Overall, 4.7% of HR+/HER2- patients and 9.9% of patients with LN removal experienced distant relapse over a median follow-up of 33.2 months (Q1-Q3: 17.0-50.6). Local relapse occurred in approximately 9.1-9.3% of patients in each group. Among the 1,175 patients with LN removal that had available pathological anatomy data, 399 (34.0%) had pathological high-risk characteristics and 13.3% experienced distant relapse. CONCLUSIONS: One in ten patients with EBC who underwent LN removal experienced a relapse, highlighting the strong need to prevent early recurrence.

Real-world analysis of the economic and therapeutic burden in advanced breast cancer patients in Italy.

BACKGROUND: This real-world analysis evaluated drug utilization focusing on wastage and healthcare costs for treatment of patients with advanced breast cancer (aBC) hormone receptor-positive (HR+)/human epidermal growth factor receptor-2 negative (HER2-) in Italy. METHODS: A retrospective analysis was conducted on administrative data covering about 13.3 million health-assisted individuals. Across January/2017-June/2021, all patients with HR+/HER2-aBC were identified by ≥ 1 prescription for cyclin-dependent kinase 4/6 inhibitors (CDK 4/6i). Cost analysis was performed and updated referring to the prices of November 2021. RESULTS: Overall, 3,647 HR+/HER2-aBC patients were included (2,627 palbociclib treated, 729 ribociclib treated, and 291 abemaciclib treated). After 12 months of follow-up, 35% of palbociclib patients had a dose reduction (on average 8.9 wasted pills/patient), 44.7% of abemaciclib patients had a dose reduction (on average 6.7 wasted pills/patient), 22.1% of ribociclib patients had a dose reduction (no wasted pills). Therapy wastage added up to 528,716€ for palbociclib-treated patients (524€/patient) and 5,738€ in abemaciclib-treated patients (151€/patient). No wastage was attributed to ribociclib. CONCLUSIONS: Dose reduction was associated with drug wastage in palbociclib and abemaciclib-treated patients, but not in ribociclib-treated ones. These findings might be helpful to policy decision-makers who, for healthcare strategies implementation, among several variables should consider the possible restraining of drug wastage.

Real-World Evaluation of the Management, Treatment Pathways and Outcome of Melanoma Patients with Target Therapies in Italy.

INTRODUCTION: In recent years, an increasing trend in the incidence of melanoma has been observed in Europe. Although early diagnosis and prompt intervention with local resection often results in positive outcomes, conversely, metastatic disease is still clinically challenging with a poor prognosis and a 5-year survival of around 30%. The growing awareness of melanoma biology and of antitumor immune responses has allowed the development of novel therapies targeted at specific molecular alterations occurring at advanced stages. This real-world analysis examined patients with melanoma in Italy, focusing on treatment patterns, outcome, time to discontinuation (TTD), and resource consumption. METHODS: Two retrospective observational analyses were conducted for BRAF+ patients with metastatic melanoma and those with a positive sentinel lymph node biopsy in an adjuvant setting, retrieving data from the administrative databases covering 13.3 million residents. The cohort melanoma BRAF+ in metastatic setting comprised 729 patients with targeted therapy (TT) (n = 671 with TT as first line and 79 as second line). RESULTS: Median TTD was 10.6 months in first line and 8.1 months in second line. Median overall survival from the start of first TT line was 27 months and was 11.8 months for patients with brain metastasis. In the dabrafenib plus trametinib patients, main healthcare resource consumption tended to increase in the presence of brain metastasis. The cohort with a positive sentinel lymph node biopsy under adjuvant therapy (n = 289) included 8% patients treated with dabrafenib plus trametinib or tested BRAF+, 5% BRAF wild-type, and 10% under immunotherapy. CONCLUSION: Our findings provided an overview on TT utilization on metastatic melanoma patients in real clinical practice and highlighted an increased burden in brain metastatic patients.

A retrospective analysis of treatment patterns, drug discontinuation and healthcare costs in Crohn's disease patients treated with biologics.

BACKGROUND/AIMS: This real-world analysis evaluated the persistence and direct healthcare costs of Crohn's Disease (CD) patients treated with biologics in Italy. METHODS: A retrospective analysis on administrative databases of Italian healthcare entities, covering 10.4 million residents, was performed. Adult CD patients under biologics between 2015 and 2020 were included and attributed to first/second treatment line based on absence/presence of biologic prescriptions 5-years before index-date (first biologic prescription). RESULTS: Of 16,374 CD patients identified, 1,398 (8.5%) were biologic-treated: 1,256 (89.8%) in first line and 135 (9.7%) in second line. Kaplan-Meier curves estimated a higher persistence for ustekinumab-treated patients followed by vedolizumab, infliximab and adalimumab, in both lines. Considering baseline variables and adalimumab as reference, infliximab in first line (HR: 0.537) and ustekinumab in first (HR: 0.057) and second line (HR: 0.213) were associated with significantly reduced risk of drug-discontinuation. First line total/average healthcare direct-costs were €13,637, €11,201, €17,104 and €18,340 in patients persistent on adalimumab, infliximab, ustekinumab and vedolizumab, respectively. CONCLUSIONS: This real-world analysis showed differences in persistence over 12-months between biologic treatments, being higher in ustekinumab-treated group, followed by vedolizumab, infliximab and adalimumab. Patients' management was associated with comparable direct healthcare costs among treatment lines, mainly driven by drug-related expenses.

[The therapeutic management and economic burden of patients with chronic kidney disease non-dialysis-dependent with anemia and ESA treated: findings from a real-world study in Italy].

Background. This real-world study aimed to provide insights on the characteristics, drug utilization, and economic burden of chronic kidney disease non-dialysis-dependent (NDD-CKD) patients with anemia prescribed Erythropoiesis Stimulating Agents (ESA) in Italian clinical practice settings. Methods. A retrospective analysis was performed based on administrative and laboratory databases covering around 1.5 million subjects across Italy. Adult patients with a record for NDD-CKD stage 3a-5 and anemia during 2014-2016 were identified. Eligibility to ESA was defined as the presence of ≥ 2 records of Hb < 11 g/dL over 6 months, and patients eligible and currently treated with ESA were included. Results. Overall, 101,143 NDD-CKD patients were screened for inclusion, of which 40,020 were anemic. A total of 25,360 anemic patients were eligible to ESA treatment and 3,238 (12.8%) were prescribed ESA and included. The mean age was 76.9 years and 51.1% was male. More frequently observed comorbidities were hypertension (over 90% in each stage), followed by diabetes (37.8-43.2%) and cardiovascular condition (20.5-28.9%). Adherence to ESA was observed in 47.9% of patients, with a downward trend while progressing across stages (from 65.8% stage 3a to 35% stage 5). A consistent proportion of patients did not have nephrology visits during the 2 years of follow-up. Costs were mainly due to all drugs (€4,391) followed by all-cause hospitalization (€3,591) and laboratory tests (€1,460). Conclusions. Findings from the study highlight an under-use of ESA in the management of anemia in NDD-CKD as well as a sub-optimal adherence to ESA and showed a great economic burden for anemic NDD-CKD patients.

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

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

Analysis of Drug Utilization in Patients with Psoriasis: A Real-World Retrospective Study Among the Italian Population.

Purpose: An Italian real-world retrospective study was conducted in patients with psoriasis (PSO) to evaluate their characteristics, treatment patterns, and biological/targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD) drug utilization. Patients and Methods: The retrospective analysis was carried out on real-world data collected from administrative databases of selected Italian health-departments; the dataset covered approximately 22% of the Italian population. PSO patients (identified by PSO hospitalization, and/or active exemption code and/or a topical anti-psoriatic medication prescription) were included. In prevalent patients identified during 2017-2018-2019-2020, baseline characteristics and treatment patterns were investigated. Moreover, b/tsDMARD drug utilization (focusing on persistence, monthly dosage, and mean duration between prescriptions) was evaluated in bionaïve patients included during 2015 and 2018. Results: PSO was diagnosed in 241,552 (in 2017), 269,856 (in 2018), 293,905 (in 2019) and 301,639 (in 2020) patients. At the index date, almost 50% of patients had not received systemic medications, and 2% had received biological treatment. Among the b/tsDMARD-treated patients, a decrease in the use of tumour necrosis factor (TNF) inhibitors (60.0-36.4%, from 2017 to 2020) and an increase in the use of interleukin (IL) inhibitors (36.3-50.6%, from 2017 to 2020) were observed. In 2018, the persistence rates of TNF inhibitors and IL inhibitors in bionaïve patients ranged from 60.8-79.7% and 83.3-87.9%, respectively. Conclusion: This real-world study of PSO drug utilization in Italy showed that a significant number of patients were not treated with systemic medications and only 2% of patients were treated with biologics. An increase in the use of IL inhibitors and a decrease in the prescription of TNF inhibitors over years were found. Patients treated with biologics were highly persistent with treatment. These data provide insight into routine clinical practice for PSO patients in Italy, suggesting that the optimization of treatment for PSO still represents an unmet medical need.

The Economic Burden of Chronic Myeloid Leukemia in Patients with Later Lines: Findings from a Real-World Analysis in Italy.

INTRODUCTION: Chronic myeloid leukemia (CML) is a hematopoietic myeloproliferative disorder that accounts for 20% of all leukemias of adults. The introduction of tyrosine kinase inhibitors (TKIs) (imatinib, bosutinib, dasatinib, nilotinib, ponatinib) has yielded significant benefits for patients with CML in terms of survival and quality of life. This real-world analysis evaluated the economic burden for managing patients with CML in 2nd or ≥ 3rd TKI lines in Italian settings of clinical practice. METHODS: A retrospective observational analysis was performed exploiting the administrative databases of a sample of entities covering around 15 million inhabitants. From 2015 to 2018, the study included adult patients with at least one prescription for TKIs, (and for some TKI with at least one hospitalization discharge diagnosis for CML, or at least one prescription for BCR-ABL examination). The index date was the first TKI prescription. Healthcare resource consumption and costs for patients with CML in 2nd and ≥ 3rd line treatment with TKIs were analyzed for drug prescriptions, hospitalizations, specialist visits, and diagnostic services. RESULTS: In total 635 patients were included, 491 in 2nd line and 144 in 3rd line with TKIs. Dasatinib was the most frequently prescribed drug in 2nd line (28.9%) and imatinib in later lines (26.4%). With progressing lines of treatment, healthcare consumption showed a trend towards increased non-TKI prescriptions per patient (8 for 2nd line and 9.7 for ≥ 3rd line). The management of patients with CML in later lines resulted in increased overall healthcare burden, with hospitalizations accounting for about half of total expenditure, whatever the treatment line and type of TKI. CONCLUSIONS: This analysis in Italian real-life clinical practice reported economic expenditure for patients with CML in 2nd or ≥ 3rd lines with TKIs, mostly burdened by hospitalizations. Such clinical complexity suggests that further efforts are needed to improve the therapeutic management of later lines of CML.

Real-World Analysis of the Therapeutic Management and Disease Burden in Chronic Myeloid Leukemia Patients with Later Lines in Italy.

Real world data are becoming a crucial tool to understand how cancer is treated in routine daily practice. This real-world analysis aims to describe the characteristics of patients with CML in 2nd or ≥3rd tyrosine kinase inhibitors (TKI) lines of therapy, to evaluate their treatment sequence and utilization in settings of Italian clinical practice in Italy. A retrospective analysis was performed using an administrative databases covering around 15.3 million cases. All adult patients prescribed with TKI as 2nd or ≥3rd lines (L) of therapy for CML during January 2015-December 2018 were included. A total of 491 patients in 2nd and 144 in ≥3rd L was included. In both cohorts, hypertension was the most reported comorbidity, followed by metabolic and blood count alterations. In each calendar inclusion year, an increment of 97.6% was observed in the number of patients treated in ≥3rd L. In the 2nd L cohort, 18.7% had a switch to 3rd L, while 26.4% of ≥3rd L patients switched to a subsequent line. Around 40% in both lines discontinued their treatment after a median time of 5.5 (2nd L) and 4.3 (≥3rd L) years. The results provided insights into CML management clinical practice, indicating a heavy disease burden for patients in later lines that showed an increasing complex management, and suggest that a need for novel treatment strategies might exists.

Analysis of the Pharmacoutilization of Biological Drugs in Psoriatic Arthritis Patients: A Real-World Retrospective Study Among an Italian Population.

INTRODUCTION: Real-world pharmacoutilization analysis of biological drugs in psoriatic arthritis (PsA) patients with the aim to evaluate biologic treatment patterns and pharmacoutilization among patients with PsA in Italy. METHODS: A retrospective study was conducted using administrative databases of Italian Entities. PsA patients were included and diagnosed by hospitalization and/or an active exemption code. Two analyses were performed: a cross-sectional for treatment patterns in patients enrolled among 2017-2020, and a longitudinal study during 2015 to investigate the pharmacoutilization, in terms of persistence and monthly maintenance dosage of biological/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs). Patients with or without b/tsDMARDs prescriptions before inclusion were defined as bioexperienced or naïve, respectively. An analysis on ixekizumab-treated patients (IXE patients) from the 2017-to study ending was performed. RESULTS: PsA was diagnosed in 24,786 (2017), 27,221 (2018), 28,889 (2019), and 29,292 (2020) patients. Across 2017-2020, 31.1-40.5% of PsA patients were untreated with systemic medications, and 16.4-18.8% were under biological therapies. Among b/tsDMARD-treated patients, decreasing use of TNF-inhibitors (77.6-57.1%) and increasing IL-inhibitors (19.6-33.2%) was found across 2017-2020, respectively. Persistence to TNF-inhibitors and IL inhibitors as first-line ranged, respectively, 74.9-83.0% and 73.0-84.6%; specifically, 73.1-76.9% and 73.0-83.8% among bio-naïve, 83.3-90.0%, and 87.0% among bio-experienced. Among IXE-patients (N = 178), 55.6% were bio-naïve, while 21.9% previously used secukinumab, 12.9% adalimumab, 10.1% etanercept. During a 1-year follow-up, 6.8% of IXE patients switched therapy. CONCLUSIONS: This real-world study of PsA pharmacoutilization in Italy showed that more than one-third of patients were systemically untreated, and almost 20% were receiving biological medications. Among biological users, increasing use of IL-inhibitors and a decrease in TNF-inhibitors prescriptions over the years were found. A rather-high extent of persistency in treatment was observed. A focused analysis on IXE patients revealed over half of them to be bio-naïve, while around one-fourth were bio-experienced to IL inhibitors.

Treatment Patterns and Pharmacoutilization in Patients Affected by Psoriasis: An Observational Study in an Italian Real-World Setting.

BACKGROUND: Real-world data can inform the use of biologics for psoriasis (PSO). OBJECTIVE: The aim was to evaluate treatment patterns and analyze pharmacoutilization in PSO patients in a real-world Italian setting, with a focus on the biologics most recently introduced. METHODS: An observational study based on administrative databases was conducted. Patients were included based on PSO diagnosis identified by either discharge diagnosis or exemption code or prescription of anti-psoriatic topical drugs (proxy of diagnosis). To describe patient characteristics and treatment patterns using the most up-to-date data, two different approaches were used: a cross-sectional study performed during 2016-2018, and a longitudinal study conducted with patients who received their first biological/targeted synthetic drugs (naïve patients) in 2014 and 2017 (the inclusion periods). RESULTS: During 2016-2018, the number of prevalent patients diagnosed with PSO was 194,054 (2016), 210,830 (2017), and 225,171 (2018). The percentage of patients receiving biologics or targeted synthetic agents ranged from 1.5 to 2.1%. Among them, naïve patients receiving interleukin (IL) inhibitors increased from 37.5% (2016) to 69.4% (2018), while those receiving anti-tumor necrosis factor (anti-TNF) decreased from 62.5% (2016) to 30.6% (2018). The longitudinal analysis included 894 and 1218 naïve patients in 2014 and 2017, respectively, of whom 7.2% (2014) and 6.9% (2017) switched therapy after a mean of 7.1 (2014) and 6.9 (2017) months. Overall, 259 patients were prescribed ixekizumab starting in 2017, of whom 73% were naïve. Ixekizumab was prescribed as monotherapy to 52.5%. CONCLUSIONS: The proportion of patients receiving biologics appeared constant over the years, with an increasing number of naïve patients being prescribed IL-17 inhibitors. Ixekizumab patients were mostly naïve.

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

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

Pattern of drug use in patients with psoriatic arthritis in Italy: study in a real-world setting.

Background: The aim of this study is to assess treatment patterns and pharmaco-utilization in patients with psoriatic arthritis (PsA) in Italy.Methods: A retrospective analysis using administrative databases of six Local Health Units was performed. All adult patients with PsA diagnosis and ≥1 prescription for biologic/targeted-synthetic (b/ts) disease-modifying antirheumatic drugs (DMARDs) from January 2010 to March 2017 were included. The date of first b/tsDMARD prescription was defined index-date. Follow-up lasted 1-year post index-date. Patients without b/tsDMARDs prescription pre index-date were defined bionaïve.Results: Of the 1,056 patients included, 33% received adalimumab, 30% etanercept, 10% golimumab, 9% secukinumab, 7% infliximab, 6% ustekinumab, 4% certolizumab, and 1% apremilast. During follow-up, persistence with b/tsDMARDs was observed in 79.8% of patients, 10.8% switched therapies, dose change occurred in 15.8% of patients, 47.4% received an add-on. Among bionaïve patients (n = 591), 67.0% were persistent with b/tsDMARDs, 10.1% switched therapy, 14.5% required a dose change and 45.8% an add-on. Discontinuation was observed in 10.6% of total PsA population and in 24.8% of bionaïve patients.Conclusion: This analysis provided insights on drug utilization patterns for PsA in an Italian real-world setting. Our results show that treatment regimen changes occur in a high proportion of PsA patients.

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

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

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

PURPOSE: To analyze the treatment patterns of psoriatic arthritis (PSA) or ankylosing spondylitis (AS) patients under biological therapies and to evaluate in this population the health-care resource consumption and related costs. PATIENTS AND METHODS: A retrospective analysis was performed on administrative databases of the Veneto region. Patients ≥18 years with at least one prescription of biological drugs and a diagnosis at any level for PSA or AS from January 1, 2011 to December 31, 2016 (inclusion period) were included. Index date (ID) was defined as date of first biological drug prescription during inclusion period. Patients were characterized the year before ID and followed-up for one year after ID. The drug utilization profile in terms of adherence, persistence and therapeutic regimen changes, and the health-care resource consumption was analyzed during follow-up. RESULTS: A total of 2602 patients were included: 1857 with PSA and 745 with AS. In the PSA cohort, 40.3% of patients were prescribed adalimumab, 35.6% etanercept, 8.0% golimumab, 7.5% infliximab, 5.6% ustekinumab and 3.0% certolizumab. Percentage of PSA patients adherent to treatment was higher among ustekinumab patients (91.3%) and lower among etanercept users (54.3%). Persistence ranged from 53.2% (infliximab) to 70.3% (etanercept). Regarding AS cohort, 45.5% of patients were prescribed adalimumab, 26% etanercept, 17.3% infliximab, 9.7% golimumab and 1.5% certolizumab. Adherence ranged from 46.9% (etanercept) to 90.9% (certolizumab) and persistence from 62.8% (adalimumab) to 81.8% (certolizumab). Mean annual health-care costs (including costs for drug treatment, diagnostic services, specialist visits and hospital admissions) ranged from €9727 (certolizumab) to €14,994 (ustekinumab) among PSA patients and from €9875 (infliximab) to €12,991 (golimumab) among AS patients. CONCLUSION: This study in Veneto region gave a picture of biological treatment patterns among PSA and AS patients in a real-world setting. Our findings showed the high degree of variability concerning utilization of each biological drug and provided insight on the economic burden of both diseases.