Search

What is Gaucher disease? Gaucher disease is a rare, inherited genetic condition. People with Gaucher disease have two non-working copies of a gene called GBA1, which contains the instructions for producing an enzyme called beta-glucosidase. Beta-glucosidase breaks down excess fatty substances called glycosphingolipids, that help maintain our cells in good working order. People with Gaucher disease do not make enough beta-glucosidase, so glycosphingolipids build up in their organs, causing complications. There are different types of Gaucher disease but most people in the Western world with Gaucher disease have type 1 (shortened to GD1). Typical complications in GD1 include having a larger spleen and liver, blood problems, and increased risk of bone problems. Bone problems, including fractures, are one of the main causes of pain and disability for people with GD1, and can impact their quality of life. Treatments such as enzyme replacement therapy (also called ERT) can reduce fracture risk but do not prevent them completely. What was the aim of this study? In this study, researchers looked at a new assessment score called the Gaucher Risk Assessment for Fracture (also known as GRAF). The aim was to evaluate how well the GRAF could predict future fracture risk in adults with GD1 who were receiving ERT. What were the findings of this study? The risk of future fractures in adults with GD1 was higher in women, and among people who had a history of bone pain or had their spleens removed as part of their treatment. Risk was also higher if people had a longer time between being diagnosed and starting treatment, and/or were older when they started ERT. The study also found that the GRAF score performed as well as other fracture risk tools used in the general population. These findings support the use of the GRAF score alongside bone density measurements and other risk factor assessments to help doctors and people with GD1 understand the risk of having a fracture after starting ERT. Clinical Trial Registration: NCT00358943 ( ClinicalTrials.gov )

Additional file 1: Table. Number and incidence rate/100 person-years (95% CI) of all causality treatment-emergent adverse events by system organ class and treatment group.

Additional file 1. Patient reported outcome measure (rmGD1-PROM).

Funder: takeda pharmaceutical company; doi: http://dx.doi.org/10.13039/100008373, BACKGROUND: Disease-specific patient-reported outcome measures (PROMs) are fundamental to understanding the impact on, and expectations of, patients with genetic disorders, and can facilitate constructive and educated conversations about treatments and outcomes. However, generic PROMs may fail to capture disease-specific concerns. Here we report the development and validation of a Gaucher disease (GD)-specific PROM for patients with type 1 Gaucher disease (GD1) a lysosomal storage disorder characterized by hepatosplenomegaly, thrombocytopenia, anemia, bruising, bone disease, and fatigue. RESULTS AND DISCUSSION: The questionnaire was initially developed with input from 85 patients or parents of patients with GD1 or GD3 in Israel. Owing to few participating patients with GD3, content validity was assessed for patients with GD1 only. Content validity of the revised questionnaire was assessed in 33 patients in the US, France, and Israel according to US Food and Drug Administration standards, with input from a panel of six GD experts and one patient advocate representative. Concept elicitation interviews explored patient experience of symptoms and treatments, and a cognitive debriefing exercise explored patients' understanding and relevance of instructions, items, response scales, and recall period. Two versions of the questionnaire were subsequently developed: a 24-item version for routine monitoring in clinical practice (rmGD1-PROM), and a 17-item version for use in clinical trials (ctGD1-PROM). Psychometric validation of the ctGD1-PROM was assessed in 46 adult patients with GD1 and re-administered two weeks later to examine test-retest reliability. Findings from the psychometric validation study revealed excellent internal consistency and strong evidence of convergent validity of the ctGD1-PROM based on correlations with the 36-item Short Form Health Survey. Most items were found to show moderate, good, or excellent test-retest reliability. CONCLUSIONS: Development of the ctGD1-PROM represents an important step forward for researchers measuring the impact of GD and its respective treatment.

Additional File 1. Gaucher Risk Assessment for Fracture Score Calculation Procedures.

Additional File 4. Supplemental Table S-IV: Skeletal Site Frequency for Pre-treatment Pediatric and Adult Fractures in GD1 Imiglucerase-treated Patients

Additional File 6. Supplemental Table S-VI: Descriptive Statistics for the Number of Fracture Sites Reported on the Dates of First and Subsequent Fractures Among Imiglucerase/Alglucerase-Treated ICGG Gaucher Registry Patients, Disease Type 1.

Additional File 3. Supplemental Table S-III: Demographic and Clinical Characteristics for Patients with Fractures after Starting Treatment with Imiglucerase/Alglucerase, Pediatric and Adult Fractures

Additional File 2. Supplemental Table S-II: Demographic and Clinical Characteristics for Patients with Fractures before Starting Treatment with Imiglucerase/Alglucerase, Pediatric and Adult Fractures