Estimating mortality in rare diseases using a population-based registry, 2002 through 2019.

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.

Real-world use of orphan medicinal products (OMPs) in rare disease (RD) patients: A population-based registry study.

Background: Despite calls for the use of real-world data, the rare diseases (RD) treatment landscape suffers from a scarcity of data referred to orphan medicinal products (OMP) use at the population level. Objectives: We aim to describe the characteristics and patterns of utilization of OMP in a sizable group of RD patients globally monitored by an area-based rare diseases registry located in the Veneto region, Italy, during a 3-year period (1 January 2019 to 31 December 2021). Methods: A list of OMP (n = 60) was assembled for study purposes, according to extensive criteria with regard to the status of orphan designation and of national reimbursement decisions. Results: OMP prescriptions involved 1,010 patients, corresponding to the 2.3% of all the patients monitored by the RD registry. Nearly one out of five (22.8%) was a pediatric patient at the time of the first prescription. OMP use interested a limited proportion (17.5%) of diseases approaching the rarity threshold, having a prevalence of less than five per 10,000, while individuals affected by these more common rare conditions represented 49% of all the patients receiving an OMP prescription. A clustering effect of OMP use was observed in selected groups of diseases, mainly, neurological, hematological, and hereditary metabolic ones. Medication plans including an OMP show in the 45.9% of the cases a high level of complexity, both in terms of nature and number of co-prescribed treatments. Off-label use interested 15.3% (n = 155) of all the RD patients with at least an OMP prescription during the study period. Conclusion: Data collected in a real-world setting through population-based registries globally monitoring RD patients, including related medication plans, have the potential to identify which diseases, and thus patients, have less benefit from the advent of OMP so far. Furthermore, in the rapidly evolving RD therapeutic landscape, they can help understand which therapeutic areas are most in need of investment to address existing unmet care needs.

[The impact of the use of treatments not included in the reimbursement classes in the care of rare patients: a real world study.] / L'impatto dell'uso dei trattamenti non compresi nelle classi di rimborsabilità nella presa in carico dei malati rari: uno studio in campo reale.

INTRODUCTION: Rare disease (RD) patients present complex therapeutic needs. When there are therapeutic options available, orphan drugs (OD) represent only a limited proportion of prescribed treatments. This study aims at investigating the real-world use of treatments considered not replaceable and essential for the care of RD patients, besides their reimbursement status, using data from a RD population-based registry. METHODS: The study is based on data derived from the Veneto region RD registry. For the period 2019-2020, we have analyzed the prescriptions of treatments defined as essential and not replaceable, besides their reimbursement status, included in therapeutic plans issued by RD expert Centres for patients resident in the Veneto region (north-east of Italy, 4.9 million inh.). The correspondent pharmaceutical costs have been estimated as well. RESULTS: In the study period there have been 22.186 prescriptions, included in 9,197 therapeutic plans issued for RD patients resident in the monitored area. The plans present a high level of complexity in terms of number and type of prescribed treatments, with 11% of the plans containing 5 or more prescriptions. 3,041 medicinal products have been prescribed in the study period, of whom 41% are drugs. Although these prescriptions are distributed among all the groups of RD patients, only a limited proportion of products (n=10) is responsible of the 50% of all the costs attributable to these treatments. Overall, the annual cost attributable to essential treatments not directly reimbursed by the national health system is quantifiable in 1 million euros per million inhabitants. CONCLUSIONS: This real-world study offers a snapshot of the complexity of treatments defined as essential, besides their reimbursement status, in therapeutic plans issued by RD expert Centres for a consistent group of RD patients monitored by a population-based registry. It highlights the complexity of the therapeutic approaches put in place for the care of RD patients, including drugs and a variety of other treatments. Population-based registries collecting data on prescribed treatments can contribute to understand the therapeutic needs of RD patients, treatments' accessibility and the impact of prescriptions on the global pharmaceutical costs.

The Epidemiology of Transition into Adulthood of Rare Diseases Patients: Results from a Population-Based Registry.

Background: Despite the fact that a considerable number of patients diagnosed with childhood-onset rare diseases (RD) survive into adulthood, limited information is available on the epidemiology of this phenomenon, which has a considerable impact both on patients' care and on the health services. This study describes the epidemiology of transition in a population of RD patients, using data from the Veneto Region Rare Diseases Registry (VRRDR), a web-based registry monitoring since 2002 a consistent number of RD in a defined area (4.9 million inhabitants). Methods: Longitudinal cohorts of patients born in the years 1988 to 1998 and enrolled in the VRRDR in their paediatric age were identified. Data referred to this group of patients, experiencing transition from paediatric to adult age during the years 2006⁻2016, are presented. Results: 2153 RD patients (44.1% females and 55.9% males) passed from childhood to adulthood in the study period, corresponding to a 3-fold increase from 2006 to 2016. The majority of these patients was affected by congenital anomalies (32.0%), by hematologic diseases (15.9%), eye disorders (12.1%) and neoplasms (7.9%). RD patients who experienced transition from paediatric age to adulthood represent the 9.2% of adult patients enrolled in the Registry at 31 December 2016. Conclusions: We described a subset of RD young adults experiencing transition into adulthood. The data reported can be considered as minimum values for estimating the size of this increasing population presenting specific transition needs. These figures are valuable for clinicians, patients and health planners. Public policy interventions are needed in order to promote dedicated care transition pathways in the broader framework of health policies devoted to RD.