The lack of head-to-head randomised trials and the consequences for patients and national health service: The case of non-small cell lung cancer.

INTRODUCTION: To introduce a drug to the market, it's not mandatory for it to be more effective and safer than the current treatment for the same condition. Consequently, head-to-head studies between the two best treatments for the same condition are not required, and this could result in a lack of information for patients, clinicians, and decision-makers. This study aims to evaluate the presence of head-to-head studies among the drugs used for the treatment of non-small cell lung cancer (NSCLC). METHODS: Taking into account the National Comprehensive Cancer Network (NCCN) guidelines updated to 2022, which list all available treatments for each NSCLC subtype, the search engine Pubmed and the platform clinicaltrials.gov were consulted to find all completed and ongoing head-to-head studies among various treatments for NSCLC. RESULTS: Among the anti-EGFR (epidermal growth factor receptor) drugs, 7 studies were found, with 6 completed and 5 registrational for drug commercialisation. No completed study to date has compared osimertinib and afatinib. For anti-ALK (anaplastic lymphoma kinase) drugs, 7 studies were found, with 5 completed. Alectinib, brigatinib, and lorlatinib have no completed comparison studies, but all were compared with crizotinib. Among various immunotherapy-based regimens, 5 studies were found, with only 1 completed. Therapeutic regimens based on pembrolizumab, atezolizumab, or the combination of nivolumab/ipilimumab have not been compared in studies published to date. CONCLUSION: There are few head-to-head studies comparing treatments for NSCLC; there are no such studies between the latest generation of drugs. Consequently, ambiguous areas exist due to the lack of comparative studies among the available evidence, preventing the clinician's choice of the most effective treatment and risking the patient receiving suboptimal therapy. Simultaneously, the price of the drug cannot be determined correctly, relying only on indirect evaluations from different trials. To dispel this uncertainty, it would be desirable to initiate a process that brings together the demands derived from clinical practice and clinical research to provide clinicians and patients with the best possible evidence.

Adherence, Persistence, Switching and Costs of Injectable and Oral Therapies for Multiple Sclerosis. Real Life Analysis Over 6 Years of Treatment.

Background: Adherence and persistence to treatment with disease-modifying therapies (DMTs) is a predictor of the efficacy of treatment. Aims: The objectives of the study were the analysis of adherence, persistence, switches, and costs of the drugs used in MS. Methods: This is a retrospective non-interventional pharmacological observational study of 610 patients diagnosed with Relapsing-Remitting Multiple Sclerosis (RRMS) under therapy between January 2007 and September 2022. Results: Adherence values were greater than 0.75 for all the drugs in considered for the study. The mean persistence value was 2.5 years on the analysis performed on the first-line treatment. Conclusion: In a therapy in which adherence is predominant, but not exclusive to therapy efficacy, persistence to the drug is synonymous with drug efficacy.

Multiple Sclerosis (MS) is a chronic disease that often begins early in life. Like in many chronic diseases, consistent adherence to treatment is vital for the long-term effectiveness of therapies. In MS, most treatments­whether oral or parenteral­are self-administered at home, making long-term adherence crucial. Persistence in sticking with a single drug is also seen as an indicator of the treatment's effectiveness, as longer use generally means fewer therapy changes and greater drug efficacy. This article analyzes these key pharmacy utilization metrics­adherence, persistence, and therapy switches­to directly compare the real-world effectiveness of the most commonly used MS drugs.

Available information about paediatric use of onco-haematological drugs authorized by EMA since 2016.

BACKGROUND: The treatment options available to children with cancer are limited. This is why for more than 10 years, the European Medicine Agency (EMA) has stated that all drugs to be marketed must be tested on the paediatric population in accordance with the Paediatric Investigation Plan (PIP). The objective of this study is to make a cross sectional analysis of the information related to the use of cancer drugs authorised on the European market in the paediatric population. METHOD: The European Public Assessment Reports and PIPs have been considered. The following data were extracted for onco-haematological drugs approved since 2016: paediatric indications, information about the paediatric population in the Summary of Product Characteristics (SmPC) and presence and characteristics of PIPs. A descriptive analysis of the characteristics of the drugs was made from the point of view of the paediatric population. RESULTS: Forty-eight drugs with onco-haematological indications have been authorised for marketing since 2016, 7 (15%) of these have paediatric indications. Two (4%) drugs have no paediatric indication but have information related to the paediatric population within SmPC. Forty-one (85%) drugs have no reference to the paediatric population in SmPC. Seventeen (35%) drugs out of 48 do not have PIPs and 11 have been granted a waiver to present the results of paediatric studies. The other 19 active ingredients have a total of 28 PIPs. CONCLUSION AND RELEVANCE: Most of the onco-haematological drugs approved by EMA since 2016 have neither paediatric indications nor mentions about paediatric use in SmPC. PIPs represent an opportunity, but demand for the paediatric population is still huge.

A multicentre study with real-world data of the use of palbociclib in the treatment of breast cancer: Treatment duration correlates with dose reductions.

OBJECTIVE: Palbociclib, a highly selective reversible CDK4-6 kinase inhibitor, is indicated in combination with an aromatase inhibitor or in combination with fulvestrant in women who had received prior endocrine treatment. Studies have demonstrated the efficacy of palbociclib in combination with fulvestrant in increasing progression-free survival in patients who relapsed or progressed on previous endocrine therapy, or in combination with aromatase inhibitor in patients who had not received previous treatments. We analysed the prescribing patterns of palbociclib in real practice correlating it with the evidence of treatment-related toxicity management and to time-to-treatment discontinuation and treatment adherence. METHODS: For the observational, retrospective study, data were collected from five Italian hospital centres that prescribed palbociclib between April 2017 and April 2020. Each centre provided data derived from an administrative database of adult patients treated with palbociclib for the two therapeutic indications.Treatment adherence was calculated using the proportion of days covered method while time-to-treatment discontinuation was defined as the difference between the first and last date treatment was administered plus the days ideally covered by the last date treatment was given. RESULTS: There were 375 patients enrolled during the study period, of whom 159 were treated with palbociclib and aromatase inhibitor and 216 were treated with palbociclib and fulvestrant. The time-to-treatment discontinuation was 8.9 months in the case of P + f (95% CI: 7.1-12.7) and 13.7 months in the case of P + ia (95% CI: 8.9-17.5). In both cohorts, treatments that received at least one dose reduction had a statistically higher time-to-treatment discontinuation than those without dose reduction (17.7 months vs. 9.2 and 16.6 vs. 7.4).The mean adherence in our study was 0.9 and remained high in treatments with one dose reduction (0.83) and this with two dose reductions (0.87). CONCLUSION: Based on these findings, it appears that the management of toxicities through reducing doses, as required by the Summary of Product Characteristics, results in a better outcome in terms of therapy duration, and therefore time to failure due to progression or toxicity.

Randomized clinical trials and real life studies: Comparison of baseline characteristics of patients in oral target therapies for renal cell carcinoma.

INTRODUCTION: Pivotal Randomized Controlled Trials (RCTs) constitute scientific evidence in support of therapeutic choices when a drug is authorized in the market. In RCTs, patients are selected in a rigorous manner, in order to avoid bias that may influence efficacy assessments. Therefore, patients who take the drug in Real Life Studies (RLSs) are not the same as those participating in RCTs, which, in turn, leads to low data transferability from RCTs to RLS. The objective of this study was to evaluate the differences between RCTs and RLS, in terms of patient baseline characteristics. MATERIALS AND METHODS: Our study includes all oral target therapies for RCC (Renal Cell Carcinoma) marketed in Europe before March 31, 2019. For each treatment, we considered both RCTs and RLSs, the former gathered from Summary of Product Characteristics published on the European Medicine Agency (EMA) website, and the latter yielded by our search in relevant literature. For each drug considered, we then compared the baseline characteristics of patients included in the RCT samples with those of the samples included in the RLSs using the Chi-squared and Mann-Whitney tests. RESULTS: We considered six medicines, for a total of 9 pivotal RCTs and 31 RLSs. RCTs reported the same type of patient baseline characteristics, whereas RLSs are more varied in reporting. Some patient baseline characteristics (metastases, previous treatments, etc.) were significantly different between RCTs and RLs. Other characteristics, such as ECOG Performance Status, brain metastases, and comorbidities, liver and kidney failure, are comprised in exclusion criteria of RCTs, though are included in RLS.Discussion and Conclusion: While evaluating equal treatments for the same indications, RCTs and RLSs do not always assess patients with the same characteristics. It would be necessary to produce evidence from RLSs so as to have an idea of treatment effectiveness in patients groups that are not eligible or underrepresented in RCTs.

Adherence to and effectiveness of lenalidomide after 1 year of treatment in a real world setting.

BACKGROUND: In combination with dexamethasone, lenalidomide is prescribed in the oral treatment of Multiple Myeloma for patients who have received at least one previous therapy. OBJECTIVE: The objective of this study is to evaluate medication adherence to lenalidomide of Multiple Myeloma patients, as well as Progression Free Survival and Overall Survival one year from the beginning of the treatment. SETTING: The study was carried out in Pescara Hospital, in Italy. All Multiple Myeloma patients who began lenalidomide therapy between January 1, 2012 and June 30, 2016 were included in our study. METHODS: Adherence to treatment was calculated by using the ratio between the Received Daily Dose and the Prescribed Daily Dose. Effectiveness in real world has been evaluated as Progression Free Survival and Overall Survival one year from the beginning of the treatment.Main outcomes measure: We assessed medication adherence and effectiveness of lenalidomide in the treatment of Multiple Myeloma. RESULTS: Adherence to the overall mean treatment was 0.73 ± 0.15, relative to 81 patients evaluated in our study. 32% of patients achieved an adherence equal to or greater than 80%. Real-life effectiveness in terms of Progression Free Survival and Overall Survival showed values of ​​53.75% and 88%, respectively, one year from the beginning of treatment. CONCLUSION: The analysis of adherence in Multiple Myeloma patients treated with lenalidomide one year from the beginning of therapy reveal a concerning lack of adherence. Moreover, the lack of correlation of the levels of adherence with patient-related variables shows that, in the case of Multiple Myeloma, adherence is not related to personal, social and environmental characteristics that may determine each patient's correct treatment implementation, but is directly influenced by disease evolution.

Drug utilisation pattern over 3 years in the real-world treatment of type II diabetes.

INTRODUCTION: Non-adherence to therapy is very common in patients with type II diabetes, leading to an increase in morbidity and mortality. The development of new oral therapies following metformin has increased the possibilities of treatment but little has been done in terms of improving medication adherence. The goal of the following study is to evaluate adherence and persistence over a period of 3 years in real-world diabetic patients and describe the comorbidities found in the group of patients studied. MATERIAL AND METHODOLOGY: A non-interventional pharmacological observational study was conducted by examining all therapies from 2011 to 2019 at a local health centre in Pescara (ASL). The medication adherence and persistence over a 3-year period were calculated using the pharmacy-refill method. The identification of the comorbidities was carried out in accordance with the Anatomical Therapeutic Chemical (ATC) Classification system at the fourth level. RESULTS: A total of 19 600 patients undergoing treatment for type II diabetes from January 2011 to December 2019 were analysed. The absolute adherence value at 3 years was 0.68 ± 0.23. The 3-year persistence curves showed a statistically significant difference (P < .0001). The ATCs with highest figures in the entire study group were: A02BC, B01AC and C10AA with 14 220, 13 934 and 10 858 patients, respectively. CONCLUSIONS: Adherence to therapy was suboptimal, while persistence curves showed a statistically significant difference, with patients treated with metformin showing better results. Comorbidities analysed showed a greater relevance of heart disease.

Real-life adherence in capecitabine therapy using two analysis methods and persistence after 6 months of treatment.

Medication adherence in the field of Oncology is crucial in therapy management and can influence the probability of achieving and maintaining efficacy over time. We conducted a cross-sectional study to evaluate adherence and persistence to oral therapy with Capecitabine, using two different calculation methods: therapy diary and indirect prescription refilling patterns. The main objective of the study was to compare the two methods of analysis and to propose a reliable adherence datum, yielded by the application of two complementary methodologies. We consequently set out to verify if data collected from therapy diaries can be superimposed to those gathered from prescription refilling patterns. Furthermore, we included data on patient-perceived quality in relation to Capecitabine therapy, as well as adverse reactions and their duration. Of 594 patients who used the study drug as of January 1, 2012, 45 completed their therapy diary. Adherence to treatment was 0.93 ± 0.10 and 0.84 ± 0.15, calculated using therapy diaries and pharmacy refill data, respectively. In terms of persistence, 53% of patients continued with treatment after six months of therapy. On a 1 to 5 scale, perceived quality was 3.31. In conclusion, when it comes to calculating adherence, it is important to preserve the objectivity of the method, which must be unencumbered by any conditioning. Regardless of the method, also considering what has already been discussed in the available literature, adherence in patients under treatment with Capecitabine, unlike persistence, is good.

Cancer drugs for solid tumors approved by the EMA since 2014: an overview of pivotal clinical trials.

INTRODUCTION: The European Medicine Agency (EMA) authorizes the marketing of drugs, with the authorization being full, conditional or issued under exceptional circumstances. Usually the efficacy and safety of drugs must be demonstrated in at least 2 well-controlled trials, but this rule is not always observed. The objective of the trial is to provide an overview of the pivotal trials of cancer drugs authorized for marketing in Europe since 2014. MATERIALS AND METHODS: From the technical data sheets of each drug authorized by the EMA between January 1, 2014 and May 31, 2019, we evaluated the relative pivotal trial(s) in terms of the following characteristics: number of patients, masking, trial phase, number of arms, primary endpoint(s), presence of subgroup analysis, quality of life as endpoint, and value of statistical p. The results provided us with the total number of trials, which we then divided into trials for orphan and non-orphan drugs. RESULTS: We considered 38 medicines, 6 of which were classified as orphans, for a total of 96 pivotal trials. Four drugs had conditional authorization, 1 was authorized under exceptional circumstances. Seventeen drugs underwent only 1 pivotal trial to support marketing authorization. Most of the trials were phase 3 and open-label, with 2 arms. Most trials considered the progression-free survival (PFS) as the primary endpoint, less than 30% of trials consider OS as a primary endpoint, and less than 40% of trials reported quality of life. The p values, with very few exceptions, were below 0.05. CONCLUSIONS: The rule of 2 well-controlled trials was complied with in just over 50% of the authorized drugs, and even when there was only 1 pivotal trial supporting the authorization, the trial itself may not have been necessarily well-controlled; the authorization was revoked for a drug because the trial did not confirm the benefits expected from confirmatory trials; while for 2 drugs, the evidence of efficacy yielded by the trials was not considered exhaustive. Considering that sometimes clinical authorization trials do not provide complete data on safety and efficacy, it would be perhaps appropriate to gather more pre-marketing evidence or leverage post-marketing data to complete the available information and have greater certainty.

Dosage adjustments in pivotal clinical trials with oral targeted therapies in solid tumors conducted in Europe.

PURPOSE: The aim of this study was to evaluate in what measure is dosage adjustment particularly prevalent in pivotal clinical trials of oral targeted therapy drugs approved by the European Medicine Agency as of July 31, 2018, for the treatment of solid tumors. METHODS: We performed a search on the official EMA site on human medicines, using as Keyword Search the ATC Code L01X (other antineoplastic agents); from the list of drugs results, we subsequently excluded antineoplastic drugs for hematological diseases, as well as refused and withdrawn drugs. For all analyzed drugs, we recorded full dosages, dose adjustments with relative reduction percentage, reason for the adjustments, number of patients included in the trial, percentage of patients who reduced their dosage or temporarily discontinued therapy, cause of dose reduction, and presence or absence of reference to a clinical outcome in patients who reduced their dose or discontinued therapy. RESULTS: We considered 74 pivotal trials on 29 target therapies, of which 56 (76%) provide information on dosage reduction, 41 (55%) on therapy suspension, and 29 (39%) on the dose taken by the sample. Trials that provide information on dosage adjustment include reduction and suspension data widely used to manage side effects; they concern, respectively, 32 and 44% of the samples considered. No trial results take account of the possible role of adjustment in clinical outcomes. CONCLUSION: It would be advisable for pivotal clinical trials to give more relevance to dose management, which is a widely used tool for the management of adverse events in clinical practice. To date, such information is lacking.

Use and costs of originator and biosimilar erythropoiesis-stimulating agents in the treatment of chemotherapy-induced anemia: real-world evidence from an Italian hospital.

The aim of this retrospective study is to evaluate adherence, switch and costs a year after the start of treatment with different erythropoietin-stimulating agents. There were 277 patients, 200 were originators (72.20%) and 77 (27.80%) were biosimilars. Adherence to treatment for originators is 0.84 ± 0.22 versus 0.76 ± 0.27 for biosimilars (p = 0.3241). Medication adherence was calculated as ratio between received daily dose to prescribed daily dose. The optimum value is 1, values less than 1 indicate loss of adherence.  The cost of treatment per year is €7365 per patient for the use of the originator drug versus €2587 for biosimilars, with a difference of €4777 per patient.

Using a treatment diary to improve the medication adherence in patients with chronic myeloid leukaemia.

PURPOSE: The aim of this study was to verify whether the distribution of a treatment diary by a pharmacist could influence the adherence to oral treatment with imatinib, nilotinib, and dasatinib in patients with chronic myeloid leukaemia. METHODS: The level of adherence was calculated using the received daily dose/prescribed daily dose ratio and compared between patients who used a diary and those who did not. RESULTS: Forty-four (35.8%) of 123 patients with chronic myeloid leukaemia completed the diary: 20 (45.4%) receiving imatinib, 17 (38.6%) receiving nilotinib, and seven (15.9%) receiving dasatinib. Treatment adherence with the diary calculated using received daily dose/prescribed daily dose method was 93.6% (imatinib 94.9%, nilotinib 91.1%, and dasatinib 95.8%). Adherence during the period without a diary was 86.5% (84.9, 87.4, and 90%). Adherence was significantly greater with than without a diary (p < 0.0001). CONCLUSIONS: The findings of this study that, in the case of chronic diseases, direct pharmacist-patient contact is important in order to maintain high levels of adherence, and a treatment diary is a valid means of doing this. According to these data, it is necessary to support similar patient-oriented programmes in order to ensure high levels of adherence and optimize drug management.

Medication Adherence to Tyrosine Kinase Inhibitors: 2-Year Analysis of Medication Adherence to Imatinib Treatment for Chronic Myeloid Leukemia and Correlation with the Depth of Molecular Response.

OBJECTIVE: Adherence to tyrosine kinase inhibitor treatment is a significant factor in the achievement of a good clinical response in chronic myeloid leukemia (CML). The aim of this retrospective study is to investigate 1- and 2-year medication adherence to imatinib treatment, linking adherence rates with the clinical outcome, in accordance with European LeukemiaNet Recommendations for the management of CML. We have tried to find a cutoff value for adherence in order to achieve a good clinical outcome. METHODS: The method used to calculate medication adherence was the ratio between the received and the prescribed daily dose. RESULTS: We observed the levels of mean adherence for each of the following response groups (in years 1 and 2, respectively): complete response (0.96, 0.95), MR4.5 (1.00, -), MR4 (0.93, 0.91), major molecular responses (0.96, 0.97), warning (0.91, 0.89) and failure (0.79, 0.84). CONCLUSION: Results show that the higher the adherence, the lower the level of BCR-ABL1. Furthermore, using cutoffs ≥0.9, outcomes were significantly improved compared to those with cutoffs <0.90. This value of adherence is in line with previous publications.

Does the presence of glenoid bone loss influence coracoid bone graft osteolysis after the Latarjet procedure? A computed tomography scan study in 2 groups of patients with and without glenoid bone loss.

BACKGROUND: Coracoid bone graft osteolysis and fibrous union are the principal causes of failure in patients treated with the Latarjet procedure. This study aims to investigate the hypothesis that coracoid bone graft osteolysis is more pronounced in cases without glenoid bone loss, which may be due to a diminished mechanotransduction effect at the bone healing site. METHODS: We prospectively followed up 34 patients, treated with a mini-plate Latarjet procedure, divided into 2 groups (group A patients had glenoid bone loss >15% and group B patients had no glenoid bone loss). A computed tomography scan evaluation with 3-dimensional reconstruction was then performed on all patients to evaluate coracoid bone graft osteolysis according to our coracoid bone graft osteolysis classification. RESULTS: The computed tomography scan analysis showed a different distribution of osteolysis between group A and group B. The statistical analysis showed a significant difference (P < .01, Bonferroni test) between groups A and B for the following sections: proximal/lateral/superficial, proximal/medial/deep, distal/lateral/superficial, and distal/lateral/deep. On average, the coracoid grafts in group A patients showed less osteolysis than the coracoid grafts in group B patients (39.6% vs 65.1%). DISCUSSION: The coracoid bone graft underwent much less osteolysis in patients with significant glenoid bone loss (>15%) than in those without it. Because factors of blood supply, compression, and surgical technique were the same for both groups, we believe that the mechanotransduction effect from the humeral head on the graft influences its remodeling. CONCLUSION: The results of this study suggest that the bone graft part of the Latarjet procedure plays a role in patients with significant coracoid bone loss but much less so when there is no bone loss.

Adherence, persistence and treatment switching in psoriasis.

Aim: This study aims to investigate drug utilization patterns in the treatment of psoriasis (PsO) from 1 to 5 years in a real-life setting with Adalimumab (Ada), Etanercept (Eta), Ustekinumab (Ust), Golimumab (Gol), Ixekizumab (Ixe), Secukinumab (Sec) and Apremilast (Apr). Materials & methods: Data from an observational study were used to calculate adherence using the Proportion of Days Covered (PDC) method and persistence. Results & conclusion: Treatment adherence was found to be good for all the drugs studied across all years of analysis, while persistence was suboptimal, showing a marked decrease from the third year of study onward. In the treatment of PsO, greater attention needs to be paid to treatment persistence.

This summary explains that when a patient follows their doctor's medication instructions and continues using the same medication over time to treat a condition like psoriasis, they can expect safer and more effective outcomes. This study examined these aspects to assess how different medications perform over the long term and to explore ways to improve their prescription. The findings highlight that the main issue is not so much in following instructions but in continuing to use the same medication throughout the treatment duration. Raising awareness among healthcare professionals about these issues is crucial to help patients maintain consistent therapy over time and improve their care pathway.

Groin Pain Syndrome Italian Consensus Conference update 2023.

Groin pain syndrome (GPS) is a controversial topic in Sports Medicine. The GPS Italian Consensus Conference on terminology, clinical evaluation and imaging assessment of groin pain in athletes was organized by the Italian Society of Arthroscopy in Milan, on 5 February 2016. In this Consensus Conference (CC) GPS etiology was divided into 11 different categories for a total of 63 pathologies. The GPS Italian Consensus Conference update 2023 is an update of the 2016 CC. The CC was based on a sequential, two-round online Delphi survey, followed by a final CC in the presence of all panelists. The panel was composed of 55 experts from different scientific and clinical backgrounds. Each expert discussed 6 different documents, one of which regarded the clinical and imaging definition of sports hernias, and the other 5 dealt with 5 new clinical situations thought to result in GPS. The panelists came to an agreement on the definition of a sports hernia. Furthermore, an agreement was reached, recognizing 4 of the 5 possible proposed pathologies as causes to GPS. On the contrary, the sixth pathology discussed did not find consensus given the insufficient evidence in the available scientific literature. The final document includes a new clinical and imaging definition of sports hernia. Furthermore, the etiology of GPS was updated compared to the previous CC of 2016. The new taxonomic classification includes 12 categories (versus 11 in the previous CC) and 67 pathologies (versus 63 in the previous CC).

Medication adherence reporting in pivotal clinical trials: overview of oral oncological drugs.

OBJECTIVES: To assess how and to what extent adherence to medication is reported in pivotal clinical trials of oral cancer drugs. METHODS: All drugs authorised by the European Medicines Agency from 1 January 2014 to 31 December 2019 were considered for analysis. For each pivotal trial we extracted the journal of publication, phase of the study, posology, mention of adherence within the main text of the published article or additional material and the terms in which the adherence was reported. RESULTS: Thirty drugs were included in the analysis from 56 clinical trials. Eleven articles (19.6%) contained a mention of medication adherence in the main document, 26 (46.4%) in the supplementary material and 19 (33.9%) did not contain any reference to adherence. Seven studies reported medication adherence between the results, expressed as number of patients discontinuing treatment for non-compliance and mean or median percentage. CONCLUSIONS: Medication adherence in pivotal clinical trials of oral oncological drugs is poorly represented. There should be a greater level of reporting in the results and it should be included among the minimum set of recommendations in reporting health research.

Healthcare Systems across Europe and the US: The Managed Entry Agreements Experience.

This systematic study aims at analyzing the differences between the approach of the European healthcare systems to the pharmaceutical market and the American one. This paper highlights the opportunities and the limitations given by the application of managed entry agreements (MEAs) in European countries as opposed to the American market, which does not regulate pharmaceutical prices. Data were collected from the Organisation for Economic Co-operation and Development (OECD), the European Medicines Agency, and the national healthcare agencies of US and European countries. A literature review was undertaken in PubMed, Scopus, MEDLINE, and Google for a period ten years (2010-2019). The period 2020-2021 was considered to compare health expenditure before and after the SARS-CoV-2 pandemic. Scarce information from national agencies has been given in terms of MEAs related to the COVID-19 pandemic. The comparison between the United States approach and the European one shows the importance of a market access regulation to reduce the cost of therapies, increasing the efficiency of national healthcare systems and the advantages in terms of quality and accessibility to the final users: patients. Nevertheless, it seems that the golden age of MEAs for Europe was during the examined period. Except for Italy, countries will move to other forms of reimbursements to obtain higher benefits, reducing the costs of an inefficient implementation and outcomes in the medium term.

Healthcare Resource Consumption and Related Costs in Patients on Antiretroviral Therapies: Findings from Real-World Data in Italy.

This real-world analysis conducted on administrative databases of a sample of Italian healthcare entities was aimed at describing the role of therapeutic pathways and drug utilization in terms of adherence, persistence, and therapy discontinuation in HIV-infected patients under antiretroviral therapies (ART) and Tenofovir Alafenamide (TAF)-based regimens on healthcare resource consumption and related direct healthcare costs. Between 2015 and 2019, adults (≥18 years) prescribed with TAF-based therapies were identified and characterized in the year prior to the first prescription (index-date) for TAF-based therapies and followed-up until the end of data availability. Overall, 2658 ART-treated patients were included, 1198 of which were under a TAF-based regimen. TAF-based therapies were associated with elevated percentages of adherence (83.3% patients with proportion of days covered, PDC > 95% and 90.6% with PDC > 85%) and persistence (78.5%). The discontinuation rate was low in TAF-treated patients, ranging from 3.3% in TAF-switchers to 5% in naïve. Persistent patients had lower overall mean annual healthcare expenditures (EUR 11,106 in persistent vs. EUR 12,380 in non-persistent, p = 0.005), and this trend was statistically significant also for costs related to HIV hospitalizations. These findings suggest that a better therapeutic management of HIV infection might result in positive clinical and economic outcomes.

Profile, Healthcare Resource Consumption and Related Costs in ANCA-Associated Vasculitis Patients: A Real-World Analysis in Italy.

INTRODUCTION: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are rare autoimmune diseases triggering inflammation of small vessels. This real-world analysis was focused on the most common AAV forms, granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), to describe patients' demographic and clinical characteristics, therapeutic management, disease progression, and the related economic burden. METHODS: A retrospective analysis was conducted on administrative databases of a representative sample of Italian healthcare entities, covering approximately 12 million residents. Between January 2010 and December 2020, adult GPA patients were identified by payment waiver code or hospitalization discharge diagnosis, and MPA patients by payment waiver code with or without hospitalization discharge diagnosis. Clinical outcomes were evaluated through AAV-related hospitalizations, renal failure onset, and mortality. Economic analysis included healthcare resource utilization deriving from drugs, hospitalizations, and outpatient specialist services. The related mean direct costs year/patient were also calculated in patients stratified by presence/absence of glucocorticoid therapy and type of inclusion criterion (hospitalization/payment waiver code). RESULTS: Overall, 859 AAV patients were divided into GPA (n = 713; 83%) and MPA (n = 146; 17%) cohorts. Outcome indicators highlighted a clinically worse phenotype associated with GPA compared to MPA. Cost analysis during follow-up showed tendentially increased expenditures in glucocorticoid-treated patients versus untreated (overall AAV: €8728 vs. €7911; GPA: €9292 vs. €9143; MPA: €5967 vs. €2390), mainly driven by drugs (AAV: €2404 vs. €874; GPA: €2510 vs. €878; MPA: €1881 vs. €854) and hospitalizations. CONCLUSION: Among AAV forms, GPA resulted in a worse clinical picture, higher mortality, and increased costs. This is the first real-world pharmaco-economic analysis on AAV patients stratified by glucocorticoid use on disease management expenditures. In both GPA and MPA patients, glucocorticoid treatment resulted in higher healthcare costs, mostly attributable to medications, and then hospitalizations, confirming the clinical complexity and economic burden for management of patients with autoimmune diseases under chronic immunosuppression.