DRUG PROVISION MANAGEMENT TO PROVIDE BETTER ACCESS TO THE HIGH COST TREATMENT AND IMPROVE OUTCOMES — EXAMPLE OF MUCOPOLYSACCHARIDOSIS TYPE II

2021 ◽  
Vol 9 (2) ◽  
pp. 6-11
Author(s):  
A.Yu. Kulikov ◽  
V.G. Serpik
Keyword(s):  
State Regulation ◽  
Comparative Assessment ◽  
Mucopolysaccharidosis Type ◽  
Type Ii ◽  
Efficacy And Safety ◽  
Mucopolysaccharidosis Type Ii ◽  
Mps Ii ◽  
Patient Register ◽  
First Choice ◽  
Drug Provision

Aim: to conduct a comparative assessment of the efficacy and safety of ERT drugs in MPS II type patients and analyze drug provision organization for pa- tients with this nosology. Methods: to conduct a comparative assessment of the efficacy and safety of ERT drugs, clinical trials data and real clinical practice data, including data from the Hunter outcomes survey register, were used. To assess the drug pro- vision organization were analyzed the current legal framework of the Russian Federation and public procurement data. Results and discussions: provision of pathogenetic therapy to the patients with orphan diseases is attributed to a number of administrative, clinical and eco- nomic constraints. The best example of the management of provision of this patients in Russia is a so-called Federal Program of High-cost nosologies (HCN) that has clear and transparent state regulation and the patient register that is essential for budget planning. The example of mucopolysaccharidosis type II (MPS II) that was included in HCN in 2019 shows noticeable increase in pa- tients’ access to therapy when transferring from regional budgets. Two medical products – idursulfase and idursulfase beta – are available in Russia for life-time pathogenetic treatment of this nosology. These products are produced using different cell lines; they have different INNs and are not interchangeable. Both drugs have registration clinical research, however, unique real world evidence is available for idursulfase only and show the survival rate of the patients with MPS II collected during 15 years of maintaining the international patient register cov- ering more than 1,000 patients from 129 countries, including Russia. According to the analysis, mortality risk in the patients treated with idursulfase is lower by 54% than in those who received no treatment (HR 0.46, 95% CI: 0.29; 0.72). This evidence can be used by health care decision makers to prioritize value of this medicinal product from both clinical and pharmacoeconomic perspectives. Predictability of therapy outcomes and higher prescription frequency according to current standards of care justifies idursulfase as a first choice treatment.

HMI-203: Gene therapy developmental candidate for mucopolysaccharidosis type II (MPS II), or Hunter syndrome

2021 ◽  
Vol 132 ◽  
pp. S147
Author(s):  
Kruti Patel ◽  
Laura Smith ◽  
Tania Seabrook ◽  
Alec Tzianabos ◽  
Lindsay Schulman ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Hunter Syndrome ◽  
Mucopolysaccharidosis Type ◽  
Type Ii ◽  
Mucopolysaccharidosis Type Ii ◽  
Mps Ii

scholarly journals The Value of Case Reports in Systematic Reviews from Rare Diseases. The Example of Enzyme Replacement Therapy (ERT) in Patients with Mucopolysaccharidosis Type II (MPS-II)

2020 ◽  
Vol 17 (18) ◽  
pp. 6590
Author(s):  
Miguel Sampayo-Cordero ◽  
Bernat Miguel-Huguet ◽  
Andrea Malfettone ◽  
José Manuel Pérez-García ◽  
Antonio Llombart-Cussac ◽  
...  
Keyword(s):  
Enzyme Replacement Therapy ◽  
Systematic Reviews ◽  
Rare Diseases ◽  
Clinical Studies ◽  
Case Reports ◽  
Mucopolysaccharidosis Type ◽  
Type Ii ◽  
Mucopolysaccharidosis Type Ii ◽  
Enzyme Replacement ◽  
Mps Ii

Background: Case reports are usually excluded from systematic reviews. Patients with rare diseases are more dependent on novel individualized strategies than patients with common diseases. We reviewed and summarized the novelties reported by case reports in mucopolysaccharidosis type II (MPS-II) patients treated with enzyme replacement therapy (ERT). Methods: We selected the case reports included in a previous meta-analysis of patients with MPS-II treated with ERT. Later clinical studies evaluating the same topic of those case reports were reported. Our primary aim was to summarize novelties reported in previous case reports. Secondary objectives analyzed the number of novelties evaluated in subsequent clinical studies and the time elapsed between the publication of the case report to the publication of the clinical study. Results: We identified 11 innovative proposals in case reports that had not been previously considered in clinical studies. Only two (18.2%) were analyzed in subsequent nonrandomized cohort studies. The other nine novelties (81.8%) were analyzed in later case reports (five) or were not included in ulterior studies (four) after more than five years from their first publication. Conclusions: Case reports should be included in systematic reviews of rare disease to obtain a comprehensive summary of the state of research and offer valuable information for healthcare practitioners.

scholarly journals Modeling Mucopolysaccharidosis Type II in the Fruit Fly by Using the RNA Interference Approach

Life ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 263
Author(s):  
Laura Rigon ◽  
Nicole Kucharowski ◽  
Franka Eckardt ◽  
Reinhard Bauer
Keyword(s):  
Rna Interference ◽  
Enzymatic Activity ◽  
Dermatan Sulfate ◽  
Fruit Fly ◽  
Neurological Involvement ◽  
Mucopolysaccharidosis Type ◽  
Type Ii ◽  
Lysosomal Storage ◽  
Mucopolysaccharidosis Type Ii ◽  
Mps Ii

Mucopolysaccharidosis type II (MPS II) is a lysosomal storage disorder that occurs due to the deficit of the lysosomal enzyme iduronate 2-sulfatase (IDS) that leads to the storage of the glycosaminoglycan heparan- and dermatan-sulfate in all organs and tissues. It is characterized by important clinical features and the severe form presents with a heavy neurological involvement. However, almost nothing is known about the neuropathogenesis of MPS II. To address this issue, we developed a ubiquitous, neuronal, and glial-specific knockdown model in Drosophila melanogaster by using the RNA interference (RNAi) approach. Knockdown of the Ids/CG12014 gene resulted in a significant reduction of the Ids gene expression and enzymatic activity. However, glycosaminoglycan storage, survival, molecular markers (Atg8a, Lamp1, Rab11), and locomotion behavior were not affected. Even strongly reduced, IDS-activity was enough to prevent a pathological phenotype in a MPS II RNAi fruit fly. Thus, a Drosophila MPS II model requires complete abolishment of the enzymatic activity.

scholarly journals Presentation and treatments for Mucopolysaccharidosis Type II (MPS II; Hunter Syndrome)

2017 ◽  
Vol 5 (4) ◽  
pp. 295-307 ◽  
Author(s):  
Molly Stapleton ◽  
Francyne Kubaski ◽  
Robert W. Mason ◽  
Hiromasa Yabe ◽  
Yasuyuki Suzuki ◽  
...  
Keyword(s):  
Hunter Syndrome ◽  
Mucopolysaccharidosis Type ◽  
Type Ii ◽  
Mucopolysaccharidosis Type Ii ◽  
Mps Ii

scholarly journals Assessment of Activity of Daily Life in Mucopolysaccharidosis Type II Patients with Hematopoietic Stem Cell Transplantation

Diagnostics ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 46 ◽  
Author(s):  
Yasuyuki Suzuki ◽  
Madeleine Taylor ◽  
Kenji Orii ◽  
Toshiyuki Fukao ◽  
Tadao Orii ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Treated Group ◽  
Level Of Care ◽  
Mucopolysaccharidosis Type ◽  
Type Ii ◽  
Mucopolysaccharidosis Type Ii ◽  
Hematopoietic Stem ◽  
Mps Ii

The effectiveness of hematopoietic stem cell transplantation (HSCT) for mucopolysaccharidosis type II (MPS II, Hunter disease) remains controversial although recent studies have shown HSCT provides more clinical impact. This study aims to evaluate the long-term effectiveness of HSCT using the activity of daily living (ADL) scores in patients with MPS II. Sixty-nine severely affected MPS II patients (19 patients who received HSCT and 50 untreated patients) and 40 attenuated affected patients (five with HSCT and 35 untreated) were investigated by a simplified ADL questionnaire. The frequency of clinical findings and the scores of ADL (verbal, gross motor, and the level of care) were analyzed statistically. The mean age of onset of 19 severely affected patients who received HSCT was 1.40 years ± 1.06, which is not statistically different from that of 50 untreated patients (p = 0.11). Macroglossia, frequent airway infection, hepatosplenomegaly, joint contracture, and sleep apnea were less frequent in the HSCT-treated group of severe MPS II patients. The severe phenotype HSCT treated group reported a statistically significant higher score of verbal function and gross motor function between the ages of 10 and 15 years and a higher level of care score between 10 and 20 years. Patients with the attenuated phenotype showed high ADL scores, and all of five HSCT treated patients reported a lower frequency of frequent airway infection, coarse skin, umbilical/inguinal hernia, hepatosplenomegaly, heart valve disorders, and carpal tunnel. In conclusion, HSCT is effective, resulting in improvements in clinical features and ADL in patients with MPS II. HSCT should be re-reviewed as a therapeutic option for MPS II patients.

scholarly journals Newborn Screening for Mucopolysaccharidosis Type II in Illinois: An Update

2020 ◽  
Vol 6 (3) ◽  
pp. 73 ◽  
Author(s):  
Barbara K. Burton ◽  
Rachel Hickey ◽  
Lauren Hitchins
Keyword(s):  
Newborn Screening ◽  
Early Years ◽  
Mucopolysaccharidosis Type ◽  
Type Ii ◽  
Lysosomal Storage ◽  
Mucopolysaccharidosis Type Ii ◽  
Effective Treatment Option ◽  
Positive Screen ◽  
Enzyme Replacement ◽  
Mps Ii

Mucopolysaccharidosis type II (MPS II, Hunter syndrome) is a rare, progressive multisystemic lysosomal storage disorder with significant morbidity and premature mortality. Infants with MPS II develop signs and symptoms of the disorder in the early years of life, yet diagnostic delays are very common. Enzyme replacement therapy is an effective treatment option. It has been shown to prolong survival and improve or stabilize many somatic manifestations of the disorder. Our initial experience with newborn screening in 162,000 infants was previously reported. Here, we update that experience with the findings in 339,269 infants. Measurement of iduronate-2-sulfatase (I2S) activity was performed on dried blood spot samples submitted for other newborn screening disorders. A positive screen was defined as I2S activity less than or equal to 10% of the daily median. In this series, 28 infants had a positive screening test result, and four other infants had a borderline result. Three positive diagnoses of MPS II were established, and 25 were diagnosed as having I2S pseudodeficiency. The natural history and the clinical features of MPS II make it an ideal target for newborn screening. Newborn screening was effective in identifying affected infants in our population with an acceptable rate of false positive results.

scholarly journals Agreement between results of meta-analyses from case reports and clinical studies, regarding efficacy and safety of idursulfase therapy in patients with mucopolysaccharidosis type II (MPS-II). A new tool for evidence-based medicine in rare diseases

2019 ◽  
Vol 14 (1) ◽  
Author(s):  
Miguel Sampayo-Cordero ◽  
Bernat Miguel-Huguet ◽  
Almudena Pardo-Mateos ◽  
Andrea Malfettone ◽  
José Pérez-García ◽  
...  
Keyword(s):  
Rare Diseases ◽  
Clinical Studies ◽  
Case Reports ◽  
Meta Analysis ◽  
Type I ◽  
Mucopolysaccharidosis Type ◽  
Type Ii ◽  
Mucopolysaccharidosis Type Ii ◽  
Mps Ii ◽  
Meta Analyses

Abstract Background A preliminary exploratory study shows solid agreement between the results of case reports and clinical study meta-analyses in mucopolysaccharidosis Type I (MPS-I) adult patients. The aim of the present study is to confirm previous results in another patient population, suffering from mucopolysaccharidosis Type II (MPS-II). Methods A systematic review and meta-analysis of case reports published by April 2018 was conducted for MPS-II patients treated with enzyme replacement therapy (ERT). The study is reported in accordance with PRISMA and MOOSE guidelines (PROSPERO database code CRD42018093408). The assessed population and outcomes were the same as previously analyzed in a meta-analysis of MPS-II clinical studies. The primary endpoint was the percent of clinical cases showing improvement in efficacy outcome, or no harm in safety outcome after ERT initiation. A restrictive procedure to aggregate case reports, by selecting standardized and well-defined outcomes, was proposed. Different sensitivity analyses were able to evaluate the robustness of results. Results Every outcome classified as “acceptable evidence group” in our case report meta-analysis had been graded as “moderate strength of evidence” in the aforementioned meta-analysis of clinical studies. Sensitivity, specificity, and positive-negative predictive values for results of both meta-analyses reached 100%, and were deemed equivalent. Conclusions Aggregating case reports quantitatively, rather than analyzing them qualitatively, may improve conclusions in rare diseases and personalized medicine. Additionally, we propose some methods to evaluate publication bias and heterogeneity of the included studies in a meta-analysis of case reports.

Sign in / Sign up

Export Citation Format

Share Document