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.The cohort consisted of all diagnosed GD patients in the Netherlands. Mutually exclusive disease states were defined as ‘asymptomatic’, ‘signs/symptoms’, ‘recovery’, ‘splenectomy’, ‘bone complication’, ‘multiple complications’ and ‘malignancy’. A natural history (NH) cohort was delineated based upon historical data on Dutch patients before ERT was available. Cumulative incidence curves were composed for progression from each disease state to the next. Two scenarios were applied for the ERT cohort: time to complications was calculated from A. start of ERT; B. entering the previous disease state.Median time for the development of signs and/or symptoms was 30.1 years (N = 73). In the NH cohort (N = 42), 9% had developed a bone complication after 10 years in the signs/symptoms phase, while 21% had undergone a splenectomy. In the ERT cohort (N = 29 (A), N = 28 (B)), 12% (A) or 4% (B) had developed a bone complication after 10 years in this phase and no patient was splenectomized. No patients in the NH cohort recovered, compared to 50% in the ERT cohort after 3.6 years (N = 28 (A)) or 22.4 years (N = 27 (B)) of treatment. Median time from a first to a second complication was 11 years in the NH cohort (N = 31), whereas 16 respectively 14 percent had developed a second complication after 10 years in the ERT cohort (N = 17, scenario A/B). Fourteen percent (scenario A/B) developed an associated malignancy after 10 years in the phase ‘multiple complications’ (N = 23). Associated malignancies occurred almost exclusively in advanced disease stages, therefore it is suggested that ERT reduces their incidenceLong-term ERT for GD can reduce the incidence of splenectomy and bone complications. As ERT prevents progression to more advanced stages of GD it will most likely result in a reduction of associated malignancies.
Highlights
Gaucher disease (GD; OMIM#230800) is an autosomal recessively inherited lysosomal storage disorder
To address the issue of effects of Enzyme replacement therapy (ERT) on long-term complications and associated conditions, we studied the progression of Gaucher disease, which can be used in a state transition model to assess the cost-effectiveness of Gaucher disease treatments
Patient cohorts A natural history cohort and an enzyme replacement therapy (ERT) cohort were defined as follows: NH cohort Enzyme replacement therapy became available in the Netherlands in April 1991
Summary
Gaucher disease (GD; OMIM#230800) is an autosomal recessively inherited lysosomal storage disorder. Controversy exists regarding its effect on bone disease, as this compartment seems slower to respond and skeletal disease may be partially unresponsive to therapy especially in a patient with a history of extensive bone manifestations before the initiation of treatment [22] Besides these effects, beneficial effects on quality of life have been demonstrated [23,24,25,26,27]. To address the issue of effects of ERT on long-term complications and associated conditions, we studied the progression of Gaucher disease, which can be used in a state transition model to assess the cost-effectiveness of Gaucher disease treatments. Such model is reported elsewhere in this journal [30]
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