The French Gaucher’s disease registry: clinical characteristics, complications and treatment of 562 patients

Abstract

BackgroundClinical features, complications and treatments of Gaucher’s disease (GD), a rare autosomal–recessive disorder due to a confirmed lysosomal enzyme (glucocerebrosidase) deficiency, are described.MethodsAll patients with known GD, living in France, with ≥1 consultations (1980–2010), were included in the French GD registry, yielding the following 4 groups: the entire cohort, with clinical description; and its subgroups: patients with ≥1 follow-up visits, to investigate complications; recently followed (2009–2010) patients; and patients treated during 2009–2010, to examine complications before and during treatment. Data are expressed as medians (range) for continuous variables and numbers (%) for categorical variables.ResultsAmong the 562 registry patients, 265 (49.6%) were females; 454 (85.0%) had type 1, 22 (4.1%) type 2, 37 (6.9%) perinatal–lethal type and 21 (3.9%) type 3. Median ages at first GD symptoms and diagnosis, respectively, were 15 (0–77) and 22 (0–84) years for all types. The first symptom diagnosing GD was splenomegaly and/or thrombocytopenia (37.6% and 26.3%, respectively). Bone-marrow aspiration and/or biopsy yielded the diagnosis for 54.7% of the patients, with enzyme deficiency confirming GD for all patients. Birth incidence rate was estimated at 1/50,000 and prevalence at 1/136,000. For the 378 followed patients, median follow-up was 16.2 (0.1–67.6) years. Major clinical complications were bone events (BE; avascular necrosis, bone infarct or pathological fracture) for 109 patients, splenectomy for 104, and Parkinson’s disease for 14; 38 patients died (neurological complications for 15 type-2 and 3 type-3 patients, GD complications for 11 type-1 and another disease for 9 type-1 patients). Forty-six had monoclonal gammopathy. Among 283 recently followed patients, 36 were untreated and 247 had been treated during 2009–2010; 216 patients received treatment in December 2010 (126 with imiglucerase, 45 velaglucerase, 24 taliglucerase, 21 miglustat). BE occurred before (130 in 67 patients) and under treatment (60 in 41 patients) with respective estimated frequencies (95% CI) of first BE at 10 years of 20.3% (14.1%–26.5%) and 19.8% (13.5%–26.1%).ConclusionThis registry enabled the epidemiological description of GD in France and showed that BE occur even during treatment.

Evaluation of Estimation Methods and Power of Tests of Discrete Covariates in Repeated Time-to-Event Parametric Models: Application to Gaucher Patients Treated by Imiglucerase

“…Our results confirmed that a BE before ERT increases the risk of a BE during ERT (24). For the next step, we should analyze the complete follow-up of patients, taking into account the initiation of ERT as a time-dependent covariate to test the impact of ERT on the change in BEs occurrence.…”

“…We used frailty model to analyze data from the FGDR (24). More precisely, we studied the occurrence of repeated BEs in Gaucher patients, since the initiation of treatment (time=0) by imiglucerase monotherapy.…”

“…Bottom: Kaplan-Meier estimate of the cumulative distribution function for the first event for high dropout for one simulated dataset of the standard scenario. The dashed lines correspond to 95% pointwise confidence intervals analysis of the first event (24). We next used a multivariate model with backward selection.…”

“…We have already studied the occurrence of the first BE after ERT initiation and the effect of several covariates. Splenectomy and having a BE before ERT were the two significant covariates found with the traditional log-rank test (24). Here we are interested in the effect of treatment on the occurrence of repeated BEs.…”

Stellungnahme der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) zur Eligustat – Nutzenbewertung gemäß § 35a SGB V des G-BA

“…Zu den skelettalen Manifestationen zählen die Infiltration des Knochenmarks mit Gaucher-Zellen, eine Verminderung der Knochendichte, avaskuläre Nekrosen, Knochenschmerzen, Gelenkzerstörungen und Spontanfrakturen. Irreversible Knochenschäden können orthopädische Eingriffe und einen Gelenkersatz nötig machen sowie zu Behinderungen führen [1,[4][5][6][7][8][9][10]. Unbehandelt reduziert die Gauchererkrankung Typ 1 die Lebenserwartung erheblich [11]; im Langzeitverlauf können zusätzlich zu den o. g. Komplikationen eine Lungenfibrose mit pulmonaler Hypertonie und eine Leberzirrhose mit portaler Hypertension sowie gehäuft multiple Myelome und B-Zelllymphome und sogar schwere Augenkomplikationen auftreten [1,2,4,8,12,13].…”