rare diseases orphan drugs epidemiology health planning
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Scopus Publications
Scopus Publications
Aging and rare diseases: from epidemiology to a call to action Monica Mazzucato, Giulia Fanton, Andrea Vianello, Cinzia Minichiello, Laura Visonà Dalla Pozza, Ema Toto, Laura Pastori, Chiara Ceolin, Marina De Rui, Alessandra Coin, Giorgio Perilongo, Giuseppe Sergi European Geriatric Medicine, 2026 Aim Aging of the general population, advances in diagnostic and therapeutic strategies, and care improvements are making rare diseases (RDs) an emerging phenomenon in the geriatric population. This study aims to provide a snapshot of the growing population of older RD patients using population-based data from the Veneto region rare disease registry (VRRDR), Italy. Methods We report the number of patients diagnosed in old age and the number of those transitioned from adulthood into old age, estimating the prevalence of older RD patients as of 31 December 2022. Finally, we analyzed the composition of their therapeutic plans. Results During the study period, 8975 patients received an RD diagnosis after 65 years of age, while 4214 patients diagnosed in their childhood or adulthood experienced the transition to old age. On 31 December 2022, there were 9508 patients aged 65 years or more residing in the study area, 20.8% of all Veneto’s RD patients. The most common groups of RDs in older patients are systemic or rheumatologic, neurologic, and skin diseases, affecting 27%, 25%, and 9% of the monitored geriatric population, respectively. Among prevalent cases, 1519 patients older than 65 years had a therapeutic plan related to their rare condition. Specifically, the most prescribed drugs were those affecting the nervous system (27.8%), the alimentary tract and metabolism (12.8%), and the antineoplastic and immuno-modulating agents (11.6%). Conclusions As older patients represent a growing number in the RD population, geriatricians and general practitioners should be involved in RD care and training programs. Further studies are needed to determine the unmet care needs of older RD patients in order to design health policies able to address the peculiar challenges posed by this group of patients emerging within the RD population.
Multidisciplinary consensus on the diagnosis and management of patients with atypical Hemolytic Uremic Syndrome (complement-mediated TMA): Recommendations from Italian scientific societies, patient associations and regulators Emma Diletta Stea, Mariateresa Pugliano, Roberta Gualtierotti, Monica Mazzucato, Luisa Santangelo, Giuseppina Annicchiarico, Alfredo Berardelli, Stefano Bianchi, Laura Bogliolo, Paolo Chiandotto, Giuseppe Cirino, Fabio De Iaco, Silvia De Rosa, Francesco Dentali, Paola Facchin, Ennio Giulio Favalli, Francesco Fiorin, Antonino Giarratano, Claudia Laterza, Francesco Macrì, Michelangelo Mancuso, Alessandro Padovani, Andrea Pasini, Annalisa Maddalena Scopinaro, Gian Domenico Sebastiani, Giorgio Sesti, Beniamino Susi, Antonio Torsello, Cinzia Vezzoni, Luca Zanlari, Loreto Gesualdo, Annamaria De Luca Pharmacological Research, 2025 Atypical Hemolytic Uremic Syndrome (aHUS) is a severe, systemic, rare disease (RD) that can occur in people of all ages, and is associated with high rates of morbidity and mortality. Because the management of patients with aHUS can be difficult, more effective strategies should be implemented. Faculty members from several Italian Scientific Societies, Patient Associations and Regional Institutional Experts on RDs met to discuss aHUS management within a multidisciplinary team (MDT), using a Delphi process to develop consensus recommendations. Consensus (≥70 % agreement by faculty members) was reached on 51 statements with the aim of improving patient management and outcomes. These statements provide a unified framework for the differential diagnosis of aHUS, prompt recognition of the pathology, referral to RD reference centers, selecting between treatment relapse prevention measures options, patient management by a MDT and improving the overall awareness of aHUS. Despite the broad scope of the consensus statements, several unmet needs in the management of patients with aHUS were identified, including diagnostic suspicion, rapid genetic investigations, regular review of the centers of expertise (considering the number of treated patients), permanent clinical referral in treatment centers and widespread expertise among adult and pediatric specialists. We hope that this standardized framework will form the basis of the "digital ecosystem" concept and development of possible information technology solutions to assist the MDT involved in the management of patients with aHUS.
Rare Diseases and epidemiology: an overlook at data from the Campania Region Rare Disease Registry (Southern Italy) A. Smimmo, E. Monda, Bruno De Rosa, M. Fordellone, Chiara De Stasio, Anna Fusco, Francesca Marzullo, M. Caiazza, Marialuisa Mazzella, Salvatore Rega, Sergio Esposito, Ferdinando Russo, Veronica Diana, Concetta Iasevoli, Maria Cristina Boccia, Sabrina Bassolino, Alberto Pagliafora, Giuseppe Fiorentino, Anna Iervolino, M. Galdo, U. Trama, Pietro Buono, Antonio Postiglione, Massimo Di Gennaro, Monica Mazzucato, Paola Facchin, Barbara Morgillo, Maria Giovanna Russo, P. Chiodini, G. Limongelli Epidemiologia E Prevenzione, 2025 OBJECTIVES to provide the epidemiological framework of those affected by rare diseases resident in the Campania Region (Southern Italy), using the data entered in the Campania Region Rare Disease Registry, acquiring information potentially useful for regional planning. DESIGN observational retrospective cohort study on patients with rare diseases included in the Regione Campania Rare Disease Registry from 01.01.2022 to 31.12.2022. SETTING AND PARTICIPANTS population included in the Rare Disease Registry and resident in the Campania Region as at 31.12.2022. MAIN OUTCOME MEASURES using the data entered in the Regione Campania Rare Disease Registry, the cumulative incidence (I) of patients with rare diseases resident in Campania was calculated, stratified by age group and rare disease group with the respective 95% confidence intervals (IC95%). Standardised cumulative provincial incidences were also calculated. These are reported using a multiplication factor of 100,000. RESULTS the incidence of patients with rare diseases in the Campania Region is 50.0 (IC95% 49.4-50.6) per 100,000 inhabitants in the year 2022. Furthermore, the rare disease groups with the highest incidence per 100,000 inhabitants are diseases of the central and peripheral nervous system (I: 8.32 per 100,000 inhabitants) and congenital malformations, chromosomopathies and genetic syndromes (I: 8.52 per 100,000 inhabitants). Moreover, the age groups in which the incidence is highest are in the paediatric age group. CONCLUSIONS an epidemiological framework of the Campania Region on rare diseases such as this one for the year 2022 is fundamental for national and regional planning in order to improve the care and quality of life of people affected by rare diseases, who often feel neglected by society. Sharing this type of information also draws attention to the need for faster diagnosis and the specialisation of new centres.
Coding undiagnosed rare disease patients in health information systems: recommendations from the RD-CODE project Céline Angin, Monica Mazzucato, Stefanie Weber, Kurt Kirch, Waed Abdel Khalek, Houda Ali, Sylvie Maiella, Annie Olry, Anne-Sophie Jannot, Ana Rath Orphanet Journal of Rare Diseases, 2024 Background In European Union countries, any disease affecting less than 5 people in 10,000 is considered rare. As expertise is scarce and rare diseases (RD) are complex, RD patients can remain undiagnosed for many years. The period of searching for a diagnosis, called diagnostic delay, sometimes leads to a diagnostic dead end when the patient’s disease is impossible to diagnose after undergoing all available investigations. In recent years, extensive efforts have been made to support the implementation of ORPHA nomenclature in health information systems (HIS) so as to allow RD coding. Until recently, the nomenclature only encompassed codes for specific RD. Persons suffering from a suspected RD who could not be diagnosed even after full investigation, could not be coded with ORPHAcodes. The recognition of the RD status is necessary for patients, even if they do not have a precise diagnosis. It can facilitate reimbursement of care, be socially and psychologically empowering, and grant them access to scientific advances. Results The RD-CODE project aimed at making those patients identifiable in HIS in order to produce crucial epidemiological data. Undiagnosed patients were defined as patients for whom no clinically-known disorder could be confirmed by an expert center after all reasonable efforts to obtain a diagnosis according to the state-of-the-art and diagnostic capabilities available. Three recommendations for the coding of undiagnosed RD patients were produced by a multi-stakeholder panel of experts: 1/ Capture the diagnostic ascertainment for all rare disease cases; 2/ Use the newly created ORPHAcode (ORPHA:616874 “Rare disorder without a determined diagnosis after full investigation”), available in the Orphanet nomenclature: as the code is new, guidelines are essential to ensure its correct and homogeneous use for undiagnosed patients’ identification in Europe and beyond; 3/ Use additional descriptors in registries. Conclusions The recommendations can now be implemented in HIS (electronic health records and/or registries) and could be a game-changer for patients, clinicians and researchers in the field, enabling assessment of the RD population, including undiagnosed patients, adaptation of policy measures including financing for care and research programs, and to improved access of undiagnosed patients to research programs.
High-cost drugs for rare diseases: their expenditure and value based on a regional area-based study Silvia Manea, Laura Visonà Dalla Pozza, Cinzia Minichiello, Linda Altieri, Monica Mazzucato, Mauro Bonin, Paola De Ambrosis, Elio Borgonovi, Paola Facchin Health Services Management Research, 2024 Background: in the field of rare diseases (RDs) most of the European studies on budget impact analysis of drugs that have been conducted often lay on theoretical assumptions and focus only on Orphan drugs (ODs). Objectives: we aimed to estimate the budget impact of specific drugs for non-oncological RDs, both ODs and non-ODs, using real-world data about patients residing in Veneto Region (Italy) and to describe its expenditure structure and dynamics. Methods: a population-based multi-source observational study was conducted using data from Regional administrative databases; an ad-hoc drugs’ list specific for RDs including both ODs and non-ODs and classifying them by ATC codes has been created. Results: In 2019, the total expenditure for drugs specific for RDs was EUR 97.2 million (6.6% of the total Regional budget). The RD drug list included 58 ATC codes, of which 15 ATC had an annual budget impact over EUR 1 million (“blockbuster drugs”). The most expensive treatment was a non-OD drug (Coagulation factor VIII). The two most represented therapeutical areas were the metabolic and the hematological ones. Conclusions: Cost analyses on RD high-cost drugs expenditure should consider any specific RD drug, not only ODs. Expenditure dynamics for RD drugs are peculiar showing “blockbuster drugs”. Some therapeutical areas seem to be lacking in the drug research field.
Estimating mortality in rare diseases using a population-based registry, 2002 through 2019 Monica Mazzucato, Laura Visonà Dalla Pozza, Cinzia Minichiello, Ema Toto, Andrea Vianello, Paola Facchin Orphanet Journal of Rare Diseases, 2023 Background Rare diseases (RD) are a heterogeneous group of diseases, sharing aspects of complexity. Prognosis is variable, even in individuals with the same disease. Real-world data on RD as a whole are scarce. The aim of this study is to provide data on mortality and survival for a substantial group of RD deriving from a population-based registry, which covers the Veneto region in Italy (4.9 million inhabitants). Results During the study period, 3367 deaths occurred, mainly in males (53.9%), elderly patients (63.5%) and patients with diseases having a reported prevalence of 1–9/100000 (65.6%). When standardizing by age, the mortality ratio was higher in RD patients than in the general population, SMR = 1.93 (95% CI 1.84–2.11), with an observed gender difference, 2.01 (95% CI 1.88–2.29) in females and 1.86 (95% CI 1.73–2.10) in males. The lowest survival rates are experienced by patients with rare neurologic diseases, rare skin diseases and rare systemic or rheumatologic diseases, 58%, 68% and 81%, respectively, after a 15-year observation period. It should be noted that only 18% of patients diagnosed with motor neuron diseases were alive after 15 years from diagnosis. Conclusions Despite progress in diagnosis, treatment and care in recent years, RD patients globally have higher mortality rates and reduced survival compared to the general population, with specific variations according to gender, age and disease group.
ORPHAcodes use for the coding of rare diseases: comparison of the accuracy and cross country comparability Monica Mazzucato, Laura Visonà Dalla Pozza, Paola Facchin, Cèline Angin, Francis Agius, Clara Cavero-Carbonell, Virginia Corrochano, Katerina Hanusova, Kurt Kirch, Deborah Lambert, Caterina Lucano, Sylvie Maiella, Monica Panzaru, Cristina Rusu, Stefanie Weber, Oscar Zurriaga, Miroslav Zvolsky, Ana Rath Orphanet Journal of Rare Diseases, 2023 Background Estimates of rare disease (RD) population impact in terms of number of affected patients and accurate disease definition is hampered by their under-representation in current coding systems. This study tested the use of a specific RD codification system (ORPHAcodes) in five European countries/regions (Czech Republic, Malta, Romania, Spain, Veneto region-Italy) across different data sources over the period January 2019-September 2021. Results Overall, 3133 ORPHAcodes were used to describe RD diagnoses, mainly corresponding to the disease/subtype of disease aggregation level of the Orphanet classification (82.2%). More than half of the ORPHAcodes (53.6%) described diseases having a very low prevalence (< 1 case per million), and most commonly captured rare developmental defects during embryogenesis (31.3%) and rare neurological diseases (17.6%). ORPHAcodes described disease entities more precisely than corresponding ICD-10 codes in 83.4% of cases. Conclusions ORPHAcodes were found to be a versatile resource for the coding of RD, able to assure easiness of use and inter-country comparability across population and hospital databases. Future research on the impact of ORPHAcoding as to the impact of numbers of RD patients with improved coding in health information systems is needed to inform on the real magnitude of this public health issue.
Breastfeeding and presence of the companion of woman’s choice during COVID-19 pandemic in Italy: regional population-based routine data and best practices at birth Francesca Zambri, Anna Maria Nannavecchia, Sonia Brescianini, Franca Rusconi, Edoardo Corsi Decenti, Monia Puglia, Martina Pacifici, Pietro Buono, Sara Cantoira, L. Gagliardi, P. Ghiotti, Olivia Leoni, Caterina Masè, Monica Mazzucato, L. Mondo, E. Pellegrini, R. Pertile, Alessandro Scoppa, Laura Visonà Dalla Pozza, A. Giusti Epidemiologia E Prevenzione, 2023 OBJECTIVES to describe the monthly trend of breastfeeding during hospitalization and the presence of companion of woman's choice during labour and birth, and the key regional responders' perspective of homogeneity/heterogeneity of the presence of the support person, before, during (February-May 2020), and after the first COVID-19 pandemic wave in a few Italian Regions. DESIGN two-phase study. SETTING AND PARTICIPANTS data from the italian birth certificate of six Italian Regions between 01.01.2019 and 31.03.2021 were analysed. Semi-structured interviews were conducted with the key regional respondents. MAIN OUTCOME MEASURES the frequency distributions of breastfeeding and the presence of companion of woman's choice were calculated as a whole and for each Region. RESULTS the infant feeding practices experienced smaller changes during COVID-19 pandemic than the presence of the companion of woman's choice during labour and birth, from January 2019 to March 2021. The highest value of exclusive breastfeeding was recorded in September 2020 (72.1%; 95%CI 71.3-72.8) in all Regions, while the lowest was recorded in March 2021 (62.5%; 95%CI 61.5-63.4). The presence of companion of woman's choice during labour and birth decreased during the pandemic and did not return to pre-pandemic levels. The highest value of presence of father during birth was recorded in March 2019 (59.0%; 95%CI 58.2-59.8), while the lowest in April 2020 (50.0%; 95%CI 49.1-50.8). The main emerging themes were: the existence of national, regional and local indications; the facilitators (e.g., Baby-Friendly Hospital Initiative implementation, strong motivation of the staff) and the critical points (e.g., inadequate analysis of the clinical-epidemiological context, inhomogeneous indications) of management of the support person presence. CONCLUSIONS the emergency has changed the provision of health services that not always guaranteed the application of best practices. It would be desirable to work for assessing the appropriateness of the birth certificate data to collect more accurate information and to provide clinical recommendations.
Pregnancy outcomes in Italy during COVID-19 pandemic: A population-based cohort study Franca Rusconi, Monia Puglia, Martina Pacifici, Sonia Brescianini, Luigi Gagliardi, Anna Maria Nannavecchia, Pietro Buono, Sara Cantoira, Sara Farchi, Michele Gobbato, Edda Pellegrini, Enrica Perrone, Riccardo Pertile, Elisa Eleonora Tavormina, Laura Visonà Dalla Pozza, Francesca Zambri, Edoardo Corsi, Debora Formisano, Olivia Leoni, Monica Mazzucato, Arianna Polo, Raffaella Rusciani, Alessandro Scoppa, and BJOG an International Journal of Obstetrics and Gynaecology, 2023
Organ donation from patients with a rare disease is often safe: the italian guidelines Bruno Dallapiccola, Stefano Moriconi, Massimo Rugge, Massimo Cardillo, Carlo Carcassi, Michele Colledan, Luca Dello Strologo, Carlo Dionisi Vici, Paola Facchin, Bruno Gridelli, Valentino La Rocca, Letizia Lombardini, Monica Mazzucato, Daniela Peritore, Antonio Amoroso Clinical Transplantation, 2022
