.
Time to treatment discontinuation (TTD) in chronic phase chronic myeloid leukemia (CML) adult Italian patients who started frontline dasatinib or nilotinib recorded in the Italian medicines agency (AIFA) monitoring registries, was explored.Median TTD and follow-up were obtained using the Kaplan-Meier and Reverse Kaplan-Meier respectively. The methodology is based on the use of an Inverse Probability Treatment Weighting (IPTW) procedure to estimate propensity scores from the gradient boosting machine algorithm (gbm) model and obtain the corresponding weights.Overall, 1526 patients were analyzed (628 treated with dasatinib and 898 with nilotinib); baseline results, in the dasatinib and in the nilotinib cohorts, show percentage of males of 56.7% and 55.8% and a median age of 57.3 and 51.9 years respectively. After a median follow-up of 4.9 years and post-adjustment, TTD was 53.5 months with dasatinib and 70.5 with nilotinib (HR 0.61, 95% CI 0.54-0.69, p<0.0001). The probability of treatment persistence at 24 and 48 months with nilotinib was 0.79 (0.77-0.82) and 0.68 (0.65-0.72), respectively, and with dasatinib was 0.73 (0.70-0.77) and 0.55 (0.51-0.60), respectively.The results showed a longer treatment persistence with frontline nilotinib, to be considered for a planned discontinuation.
In Italy, praziquantel (PZQ) is not registered for human use and can be imported from European countries where it is authorized, according to a specific ministerial decree. Recent Europe-wide shortages, however, have made this route impractical, resulting in the unavailability of this essential medicine. This editorial summarizes historical gaps in supply, the actions undertaken, and the interim solutions implemented to restore PZQ access in Italy. The Italian experience highlights broader challenges related to essential medicines and underscores the need for coordinated national and European strategies to ensure stable and equitable availability.
INTRODUCTION:Italian Cystic Fibrosis Registry (ICFR) collects data of people with cystic fibrosis through the collaboration with Italian CF referral and support Centres (Italian law 548/93). It aims at analysing medium and long-term clinical and epidemiological trends, identifying healthcare needs at regional and national levels, contributing to healthcare programs and resource allocation (sharing the population of FC centres with the Ministry of Health). Finally, the RIFC shares some of its data with the Italian Medicines Agency (Agenzia Italiana del Farmaco, AIFA) to better define the number of people with cystic fibrosis with early access to specific treatments with innovative therapies. Moreover, ICFR data are shared with the European CF Patients' Registry (ECFSPs' Registry) to contribute to the estimation of the European incidence of the pathology and to bridge knowledge gaps on specific topics as well as to the adoption of common strategies for the standardized collection of data on people with cystic fibrosis. OBJECTIVES:The objective of this report is to provide updated data from ICFR for the years 2023 and 2024. It is essential to consider that the analyses and specific studies carried out refer to a limited number of variables collected in the Registry, and that the selection of the topics covered in the chapters of this report was agreed by the scientific committee of the ICFR. STUDY DESIGN:The analyses and results presented in this report pertain to people with cystic fibrosis currently under care Italian National Referral Centres (CRR) and Support Centres (SS) for Cystic Fibrosis and Paediatric Hospital 'Bambino Gesù' (OPBG). Data are collected using web-based software adopted by almost all participating centres, except for the centres in Verona (which also includes the data from Treviso and Rovereto) and Messina, where data collection is carried out using a different software. The submitted data are then subject to both quantitative and qualitative quality control (QC) procedures, aimed at verifying the consistency and continuity of the information previously transmitted and shared with the European CF Registry. SETTING AND PARTICIPANTS:In the two-year period 2023-2024, 28 and 27 CF Centres, respectively, submitted their data to ICFR. However, the information from the two CF centres in Sardinia is still partial, since the data provided is limited to a small number of people with cystic fibrosis from 2023. RESULTS:The results section provides a comprehensive overview of various aspects of CF epidemiology and people with cystic fibrosis characteristics. 1. Demography: in 2023 and 2024, 6,127 and 6,182 people with cystic fibrosis were, respectively, included in the ICFR (median ages of 24.1 and 24.9 years). On average, 52.2% of people with cystic fibrosis are male, and most of the population (65.3%) is older than 18 years. This reflects the growth of the adult population, the number of paediatric people with cystic fibrosis remains almost unchanged compared to previous years. 2. DIAGNOSES:in 2024, 66.5% of the Italian CF population received a diagnosis before reaching two years of age, 61.8% within the first year of life, while 15.5% of diagnoses were made in adulthood (>18 years). New diagnoses were 103 in 2023 and 134 in 2024, with an incidence of 1 in 5,587 live births in 2023 and 1 in 8,808 in 2024. 3. GENETICS:the genetic analysis of people with cystic fibrosis was performed in 99.9% of cases. The results allowed the characterization of at least one of the two alleles in 6,040 individuals (97.7%). The most frequent variant in Italy, consistent with previous years, is F508del, present in 43.6% of cases. A higher frequency, compared with other European countries, is also confirmed for the genetic variants N1303K, G542X, and 2789+5G>A. Only 1.3% of alleles carry a CFTR gene variant that has not yet been identified (unknown). 4. Lung function: lung function, measured by percent predicted FEV1%p, declined progressively before adulthood. In detail, 96.4% (in 2023) and 95.5% (in 2024) of paediatric people with cystic fibrosis aged between 6 and 17 maintain a FEV1%p>=70%. On the other hand, the percentage of paediatric people with cystic fibrosis with severely impaired respiratory function (FEV1%p<40%) is 0.2% (2023) and 0.1% (2024). In the adult population, FEV1%p values are encouraging, with an increasing proportion of people with cystic fibrosis showing preserved lung function (85.7% in 2023 and 87.1% in 2024). This report introduces a brief focus on pulmonary exacerbations, which decreased between 2023 and 2024 (from 19.8% to 15.4%; recurrent forms from 8.6% to 4.9%), with reductions across all age groups, though less marked in those over 40. The most affected remain children (1-6 years) and those over 55; the 4.9% with recurrent episodes represent the priority for therapeutic optimization. Overall, trends in respiratory function suggest a progressive improvement in health status among the adult population, likely associated with the increasing use of new targeted pharmacological therapies. 5. Nutrition: ICFR data confirm the critical nature of the first months of life, which usually precede the definitive diagnosis of CF and the subsequent initiation of specialized care. In the 12-17 years age group, the median body max index (BMI) z-score is close to zero, documenting an adequate nutritional status in half of the subjects. The proportion of malnourished males was 6.2% and 5%, while among females it was 2.3% and 2.6%, respectively, in 2023 and 2024. In the >=18 years age group, a higher percentage of underweight BMI is observed among females (9% in 2023 and 8% in 2024) compared with males (4.2% and 4.4% in 2023 and 2024, respectively). 6. COMPLICATIONS:in 2024, in both paediatric and adult people with cystic fibrosis, the most frequent complications were the same, but occurred at different rates, such as CF-related liver disease (24.1% and 49.4%, respectively), diabetes (3.8% and 26%), and osteoporosis (4.2% and 18.7%). A total of 50 people with cystic fibrosis with cancer were recorded in 2023 and 2024, of whom 4 were of paediatric age. 7. Transplantation: over the two-year period, 21 people with cystic fibrosis underwent double-lung transplantation, with median ages of 36.2 e 36.8 years in 2023 and 2024, respectively, with ages ranging from 15.1 to 64.7 years across the two years. 8. Microbiology: in 2024, the prevalence of adult people with cystic fibrosis with chronic Pseudomonas aeruginosa infection is 30.1%, while in paediatric people with cystic fibrosis is 5.5%. The prevalence of Staphylococcus aureus infections is 28.7% and 26.4%, respectively, in adults and paediatric people with cystic fibrosis; prevalence of infections of Burkholderia cepacia is 1.6% and 0.2%. 9. MORTALITY:in the two-year period, ICFR data show that 36 people with cystic fibrosis died (16 males and 20 females), with median ages at death of 48.3 years in 2023 and 57.2 years in 2024 (excluding transplanted people with cystic fibrosis). The crude mortality rate ranged from 3.1‰ in 2023 to 2.8‰ in 2024; excluding transplant recipients, the crude rate was 1.6‰ and 1.0‰ in the respective years. 10. Motherhood and fatherhood: over the two-year period, 80 pregnancies were recorded, of which 62 were successfully completed (77.5%). Additionally, 22 pregnancies were still ongoing as of 31.12.2024. In 2024, 25 people with cystic fibrosis became fathers. CONCLUSIONS:The present report updates data published in previous years thus summarizing 2023 and 2024 results. The number of registered people with cystic fibrosis was 6,127 in 2023 and 6,182 in 2024. Population coverage estimates for 2024 to be around 98%. Over the two-year period 2023-2024, the number and percentage of people with cystic fibrosis aged over 18 years increased. In detail, the ICFR recorded 3,927 adult people with cystic fibrosis (64.1%) in 2023 and 4,034 (65.3%) in 2024. An increase in the median age of Italian people with cystic fibrosis has been observed over time, reaching 24.9 years in 2024. The absolute number of new diagnoses per year is comparable with that of the previous biennium (237 vs 234); the percentage of new diagnosis in adulthood was 39.6% in 2024. In 2024, the median age at diagnosis was 3.9 months; 61.8% of subjects are diagnosed within the first year of life; 95.1% of them were identified through neonatal screening. Analysis of different CFTR genotypes in the Italian CF population confirms the high allelic variability observed in Italy, with a substantial proportion of subjects not eligible for CFTR modulator therapy. Regarding respiratory function, findings are consistent with previous reports, showing an increasing percentage of subjects under the age of 18 with a normal respiratory function. This marked improvement observed in the adult population seems to be mainly due to the introduction of highly effective CFTR modulator therapies in Italy from 2021. In 2024, a reduction in the percentage of chronic Pseudomonas aeruginosa infection was observed in both adults (30.1% vs 38.8% in 2020) and paediatric people with cystic fibrosis (5.5% vs 7.6% in 2020). Liver disease remains the most frequent complication in both paediatric and adult populations, affecting 24.1% and 49.4% of people with cystic fibrosis, respectively. During the two-year period, 36 people with cystic fibrosis died with a median age at death between 48.3 and 57.2 years (transplant people with cystic fibrosis excluded). Only one transplanted people with cystic fibrosis under the age of 18 died in the period 2023 and 2024, confirming once again that mortality in paediatric age is a rare event. Finally, for the first time, this report introduces data related to maternity and paternity, highlighting that in more than 77% of cases pregnancies were successful; as well as estimates of tumour and pulmonary exacerbations incidence as possible complications.
BACKGROUND:Time to treatment discontinuation (TTD) in chronic phase chronic myeloid leukemia (CML) adult Italian patients who started frontline dasatinib or nilotinib recorded in the Italian medicines agency (AIFA) monitoring registries, was explored. MATERIAL AND METHODS:Median TTD and follow-up were obtained using the Kaplan-Meier and Reverse Kaplan-Meier respectively. The methodology is based on the use of an Inverse Probability Treatment Weighting (IPTW) procedure to estimate propensity scores from the gradient boosting machine algorithm (gbm) model and obtain the corresponding weights. RESULTS:Overall, 1526 patients were analyzed (628 treated with dasatinib and 898 with nilotinib); baseline results, in the dasatinib and in the nilotinib cohorts, show percentage of males of 56.7% and 55.8% and a median age of 57.3 and 51.9 years respectively. After a median follow-up of 4.9 years and post-adjustment, TTD was 53.5 months with dasatinib and 70.5 with nilotinib (HR 0.61, 95% CI 0.54-0.69, p<0.0001). The probability of treatment persistence at 24 and 48 months with nilotinib was 0.79 (0.77-0.82) and 0.68 (0.65-0.72), respectively, and with dasatinib was 0.73 (0.70-0.77) and 0.55 (0.51-0.60), respectively. CONCLUSION:The results showed a longer treatment persistence with frontline nilotinib, to be considered for a planned discontinuation.
