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

Michael L Ganz,Alex Ward,Martin Selzer,Sean Stern,Luba Nalysnyk,Neal Weinreb,Alaa Hamed

doi:10.1186/s13023-017-0592-6

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 registrationNCT01136304. Registered: May 31, 2010 (retrospectively registered).

Highlights

The Disease Severity Scoring System (DS3) is a validated measure for evaluating Gaucher disease type 1 (GD1) severity
We developed a new framework based on the Disease Severity Scoring System (DS3), a validated measure for evaluating GD1 severity, to address some of the limitations in the current literature [11]
We found that the three broad severity categories of moderate, marked, and severe had increasingly larger negative effects on health-state utility compared with the mild severity category

Summary

Introduction

The Disease Severity Scoring System (DS3) is a validated measure for evaluating Gaucher disease type 1 (GD1) severity. 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). Presentation of the disease is variable, but is typically characterized by visceral problems such as Current therapeutic options with regulatory approval in either the United States (US) or Europe include intravenous enzyme replacement therapy (ERT) with imiglucerase, velaglucerase alfa, or (in the US only) taliglucerase alfa or oral substrate reduction therapy (SRT) with eliglustat or miglustat [7]. Eliglustat, the most recently licensed oral SRT with comparable efficacy to imiglucerase and a favorable safety profile, is approved in the US (2014) and Europe (2015) as a first-line therapy for treatment-naïve and ERT-treated adults with GD1. Eliglustat should be avoided in patients who are pregnant or breast feeding, who have advanced liver, kidney or cardiac disease as it has not been studied in these populations

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