The International Collaborative Gaucher Group GRAF (Gaucher Risk Assessment for Fracture) score: a composite risk score for assessing adult fracture risk in imiglucerase‑treated Gaucher disease type 1 patients

Orphanet J Rare Dis. 2021 Feb 18;16(1):92. doi: 10.1186/s13023-020-01656-6.

PMID: 33602299

Patrick Deegan, Aneal Khan, José Simon Camelo Jr, Julie L. Batista and Neal Weinreb

Summary: The aim of this study was to create a risk score assessment GRAF as a clinical tool for determining risk for future fractures beyond standard risk factors that change with time and treatment in Gaucher disease type 1 patients. The GRAF score can be used to inform clinicians about the potential fracture risk after starting imiglucerase or other alternative ERTs.

Abstract

Objective: The aim of this study was to create a risk score assessment (the Gaucher Risk Assessment for Fracture [GRAF]) as a clinical tool for determining risk for future fractures beyond standard risk factors that change with time and treatment in Gaucher disease type 1 (GD1) patients. This tool uses 5 commonly available characteristics (sex, age at treatment initiation [ATI], time interval between diagnosis and treatment initiation, splenectomy status, history of pre-treatment bone crisis) to assess potential fracture risk when imiglucerase enzyme replacement therapy (ERT) is started.

Methods: 3216 of 6422 GD1 patients were included in the study from the International Collaborative Gaucher Group Gaucher Registry as of September 2019. Inclusion criteria were primary treatment with alglucerase/imiglucerase; known splenectomy status; at least one skeletal assessment on treatment. Data were analyzed using Cox proportional hazards regression with all 5 risk factors included in the model for each ATI category (< 18, ≥ 18 to < 50, or ≥ 50 years of age). The contribution of each parameter was weighted by the strength of its association (regression coefficient) with fracture risk to produce a composite risk score.

Results: Follow-up period was from the date of treatment initiation (or age 18 years for patients who started treatment earlier) to the date of first adult fracture (n = 288 first fracture endpoints), death, or end of follow-up. Each 1-point increase in the GRAF score was associated with a 2.7-fold increased risk of fracture in adulthood (p<0.02 for <18 ATI, p<0.0001 for ≥18 to <50 ATI and ≥50 ATI).

Conclusions: The GRAF score is a tool that can be used in conjunction with bone density and other modifiable, non-GD-specific risk factors (e.g., smoking, alcohol intake, frailty) to warn clinicians and previously untreated GD1 patients about risk of a future fracture after starting imiglucerase or other alternative ERTs. GRAF can also estimate how much the risk of fracture will rise with the delay of treatment initiation.