A new framework for evaluating the health impacts of treatment for Gaucher disease type 1

Abstract

BackgroundThe Disease Severity Scoring System (DS3) is a validated measure for evaluating Gaucher disease type 1 (GD1) severity. We developed a new framework, consisting of health states, transition probabilities between those states, and preferences for those states (utilities) based on the DS3 to predict long-term outcomes of patients starting treatment. We defined nine mutually exclusive (alive) health states based on three DS3 categories: mild (0 ≤ DS3 ≤ 3.5) without symptoms of bone disease; mild with bone pain, mild with severe skeletal complications (SSC) defined as lytic lesions, avascular necrosis, or fracture; moderate (3.5 < DS3 ≤ 6.5) without SSC; moderate with SSC; marked (6.5 < DS3 ≤ 9.5) without SSC; marked with SSC; severe (9.5 < DS3 ≤ 19) without SSC; and severe with SSC. Health-state transition probabilities and utilities were estimated from a longitudinal sample of patients with GD1 who started enzyme replacement therapy (the DS3 Score Study). Age dependent GD1-specific mortality was derived from published data. We used a Markov state-transition model to illustrate how to estimate time spent in each health state.ResultsThe average predicted utilities for each health state ranged from 0.76 for mild disease with no clinical symptoms of bone disease to 0.52 with severe disease with SSC. Transition probabilities depended on disease severity (DS3 score) at treatment initiation and whether patients had undergone a total splenectomy or had an intact spleen/partial splenectomy prior to starting treatment. Patients who started treatment with intact or residual spleens spent more time in better health states than those who started treatment with total splenectomy.ConclusionsThis new framework, which is based on the DS3, can be used to project the long-term outcomes of GD1 patients starting treatment. The framework could also be used to compare the long-term outcomes of different GD1 treatment options.Trial registration NCT01136304. Registered: May 31, 2010 (retrospectively registered).Electronic supplementary materialThe online version of this article (doi:10.1186/s13023-017-0592-6) contains supplementary material, which is available to authorized users.

A health state utility valuation study to assess the impact of treatment mode of administration in Gaucher disease

“…However, the purpose of the present study was to focus on specific known attributes related to the modes of treatment administration rather than the disease itself. The exploration of utilities related to various disease states in GD1 was already published by Ganz et al [ 39 ]. Still, attempts were made to ensure that the health state descriptions were as representative as possible, but we cannot exclude the possibility of having overlooked some issues of importance to patients.…”

Insights into the Value of Lyso-Gb1 as a Predictive Biomarker in Treatment-Naïve Patients with Gaucher Disease Type 1 in the LYSO-PROOF Study

“…In contrast, the cohort with GD patients that could not be classified (n = 46) due to having previously unreported genotypes had a decreased mean onset of 10 years (median: 6 years; IQR [2][3][4][5][6][7][8][9][10][11][12][13]) (Figure 2). p.Asn409Ser/p.Leu483Pro (n = 13) have a decreased mean onset of only 24 years (median: 20 years; IQR ) (Figure 2).…”

“…The disease severity scoring system (DS3) is an established and validated measure for evaluating GD1 severity based on bone, hematologic, and visceral domains [5][6][7]. Disease severity states are defined as mild (DS3 < 3.0), moderate (DS3 3.0-6.0), marked (DS3 6.0-9.0), and severe (DS3 9.0-19.0) [5].…”

“…To more precisely measure and assess clinical symptoms and disease severity (burden of disease) in patients with GD1, a disease severity scoring system (GD-DS3) has been introduced [5,6]. GD-DS3 is a validated measure for GD1 disease severity based on bone, hematologic, and visceral domains, which can be used to monitor long-term outcomes of patients starting treatment [7].…”

Enfermedad de Gaucher: una enfermedad multisistémica

“…El seguimiento de los pacientes con tratamiento lo establece un documento de consenso, publicado por un grupo de trabajo europeo, con los objetivos a corto y largo plazo 15 (Tabla 1). Asimismo, existe un nuevo sistema de puntuación de gravedad de la enfermedad (DS3), utilizado para valorar los resultados de salud a largo plazo de las personas con EG1 16 . Existen dos opciones aprobadas para el tratamiento en la EG: tratamiento de reemplazamiento enzimático (TRE) y de reducción de sustrato (TRS).…”