Orphan Drug Use in Patients With Rare Diseases: A Population-Based Cohort Study

Abstract

Background: Orphan drugs are used for the diagnosis, prevention and treatment of rare diseases that, in the European Union, are defined as disorders affecting no more than 5 persons in 10,000. So far, a total of around 800 orphan medicinal products have been approved by the European Medicines Agency, however the utilization profile of orphan drugs has yet to be explored. This study aimed at assessing the utilization profile of orphan drugs authorized for marketing by the Italian Medicines Agency using population-based data.Methods: A total of 21 orphan drugs used in outpatient settings, approved in the European Union before or during the 2008–2018 period and involving 15 rare diseases, were included in the study. The monitored population included patients with one of the conditions surveilled by the population-based Tuscany Registry of Rare Diseases and diagnosed between 2000–2018. A multi-database approach was applied, by linking data from the registry with information collected in drug prescriptions databases. The prevalence and intensity of use were estimated for the selected orphan drugs and other non-orphan medications, used to treat the same rare disease and for which a change in the prevalence of use was hypothesized after authorization of the orphan drug.Results: For some diseases (acquired aplastic anemia, tuberous sclerosis complex, most metabolic diseases) a low prevalence of orphan drugs use was observed (range between 1.1–12.5%). Conversely, orphan drugs were frequently used in hemophilia B, Wilson disease and idiopathic pulmonary fibrosis (maximum of 78.3, 47.6 and 41.8%, respectively). For hemophilia B and Leber’s hereditary optic neuropathy, there are currently no other medications used in clinical practice in addition to orphan drugs. Six orphan drugs were used for the treatment of pulmonary arterial hypertension, appearing the elective therapy for this disease, albeit with different utilization profiles (range of prevalence 1.7–55.6%).Conclusion: To the best of our knowledge, this is the first study investigating the utilization profile of orphan drugs prescribed in a defined geographical area, and providing relevant information to monitor over time potential changes in the prevalence of these medications as well as in the health care decision making.

Self-Reported Medication Adherence Measured with Morisky Scales in Rare Disease Patients: A Systematic Review and Meta-Analysis

“…However, the difficulties presented by this type of patient, both physical and psychological, may impact adherence rate being not as high as it should be. In patients with RDs, poor adherence or treatment interruption will lead to a worsening of the disease itself [54].…”

Profile of Drug Utilization in Patients with Rare Diseases in Tuscany, Italy: A Population-Based Study

“…(2) the prescriptions/users (Pr/Us) ratio, a measure of intensity of use, was calculated by dividing the total number of prescriptions of drugs belonging to each therapeutic category by the number of users (cases with at least one prescription) in the same therapeutic category and in the same year [16,17]; (3) the total defined daily dose (DDD, the assumed average maintenance dose per day for a drug used as per its main indication in adults) utilized, on average, on any given day of the year and analyzed in a group of 1000 cases (DDD/1000 cases per day) [18]. The DDDs were not calculated for the following categories/subgroups, according to the guidelines (https://www.whocc.no/atc_ddd_index/, accessed on 15 October 2022): A15-appetite stimulants; B05-blood substitutes and perfusion solutions; C05-vasoprotectives; D-dermatologicals; J06-immune sera and immunoglobulins (except for nebacumab in J06BC01); J07-vaccines; L01-antineoplastic agents (except for the protein kinase inhibitors in L01E only); P03-ectoparasiticides, incl.…”

Organic Aciduria Disorders in Pregnancy: An Overview of Metabolic Considerations

“…Expert opinions advise against the primary use of sodium phenylbutyrate as an ammonia scavenger in MMA and PA during acute metabolic decompensation [8,10]. There is still limited evidence on the long-term efficacy of carglumic acid in MMA [78]. Recent evidence suggests that taking carglumic acid in addition to standard treatment may significantly reduce the number of emergency admissions related to hyperammonaemia in patients with PA and MMA [79].…”