Modelling Gaucher disease progression: long-term enzyme replacement therapy reduces the incidence of splenectomy and bone complications

Abstract

Long-term complications and associated conditions of type 1 Gaucher Disease (GD) can include splenectomy, bone complications, pulmonary hypertension, Parkinson disease and malignancies. Enzyme replacement therapy (ERT) reverses cytopenia and reduces organomegaly. To study the effects of ERT on long-term complications and associated conditions, the course of Gaucher disease was modelled.

Figure 1

Multi-state diagram of our proposed model. Please note that this diagram represents both the NH chohort as well as the ERT cohort, with two exceptions: 1: recovery was not observed in the NH cohort. 2: the ERT cohort has no asymptomatic state as asymptomatic patients are not treated.

Figure 2

Cumulative incidence of bone complications in untreated and treated patients with signs/symptoms. a. scenario A, untreated N=42, treated N=29, b. scenario B, untreated (N = 42), treated (N = 28).

Figure 3

Cumulative incidence of spenectomies in untreated and treated patients with signs/symptoms. a. Scenario A, untreated N = 42, treated N = 29 b. Scenario B, untreated N = 42, treated N = 28.

Figure 4

Cumulative incidence of recoveries in untreated and treated patients with signs/symptoms. a. Scenario A, untreated (N = 42), treated (N = 28). b. Scenario B, untreated N=42, treated N=27.

Figure 5

Cumulative incidence of second complications in untreated and treated patients with a first complications. a. Scenario A, untreated N=31, treated N=17 b. Scenario B, untreated N = 31, treated N = 17.

Figure 6

Cumulative incidence of malignancies in treated patients with multiple complications. a. Scenario A, N=23 b. Scenario B, N=23.

Figure 7

Flow-chart of the NH cohort. Please note that two patients who remained asymptomatic during follow-up were excluded from the analysis as both patient where diagnosed because of family studies. Two patients who started treatment while asymptomatic where excluded because the reasons/circumstances for starting treatment differed from other patients (e.g. patients’ wish).

Figure 8

Flow-chart of the ERT cohort, start of follow-up = start ERT.

Figure 9

Flow-chart of the ERT cohort, start follow-up = start phase (in contrast to start ERT).

Figure 10

Cumulative incidence of signs/symptoms in asymptomatic patients (N = 73).

Figure 11

Cumulative survival in the entire study cohort, irrespective of treatment status, treatment duration, and cause of death (N = 90). Red lines represent the NH cohort, black lines represent the ERT cohort. LCL: lower confidence limit. UCL: upper confidence limit.