Real-world clinical experience with long-term miglustat maintenance therapy in type 1 Gaucher disease: the ZAGAL project

Giraldo, Pilar; Alfonso, Pilar; Atutxa, Koldo; Fernandez‐Galan, M. Angeles; Bárez, Abelardo; Franco, Rafael; Alonso, Dora; Martı́n, Alejandro; Latre, Paz; Pocovı́, Miguel

doi:10.3324/haematol.2009.008078

Cited by 67 publications

(69 citation statements)

References 22 publications

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“…No AVN or bone fractures were reported during the 2-year observational period, and BMD Z-scores improved from baseline at both the lumbar spine and femoral neck at each time point (months 6, 12, and 24) [105]. A prospective open-label investigational study, which evaluated the therapy with miglustat 100 mg in patients with Type 1 GD, reported an improvement of bone marrow infiltration by 2.9 points measured by S-MRI score in 28 patients [106].…”

Section: Substrate Reduction Therapymentioning

confidence: 93%

Gaucher Disease and Bone Manifestations

et al. 2014

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Gaucher disease is a relatively rare metabolic disease caused by the inherited deficiency of the lysosomal enzyme glucocerebrosidase. Gaucher disease affects multiple organs, among which is the skeleton. Bone involvement occurs frequently in Gaucher disease, and is one of its most debilitating features, reducing the quality of life of patients. Bone status is an important consideration for treatment to ameliorate symptoms and reduce the risk of irreversible complications. We have conducted a systematic review of all the various aspects of Gaucher disease, focusing on different skeletal manifestations, pathophysiology of bone alterations, clinical symptoms, and current diagnostic and therapeutic approaches.

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Section: Substrate Reduction Therapymentioning

confidence: 93%

Gaucher Disease and Bone Manifestations

et al. 2014

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“…These scoring systems, such as BMB or S-MRI [43][44][45], can be regarded as a good alternative to QCSI in daily routine [39,43]. Studies have shown an improvement in bone marrow involvement on ERT [46][47][48] and SRT [49] using either the BMB or S-MRI scoring system. Thus, these scoring systems are regarded to be beneficial in evaluating the extent of bone involvement of GD patients prior to therapy and during follow-up in order to quantify changes of bone involvement due to treatment.…”

Section: X-raymentioning

confidence: 97%

“…Results regarding the effects of SRT on bone disease in GD1 are limited so far [49,79,81,82]. Similar to ERT, SRT also showed a positive effect on bone pain and bone crisis.…”

Section: Srtmentioning

confidence: 99%

An overview on bone manifestations in Gaucher disease

Mikosch

Hughes

2010

Wien Med Wochenschr

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Gaucher disease (GD), the most prevalent lysosomal storage disorder, affects multiple organ systems. Patients with non-neuronopathic (type 1) GD, the most common form of GD, present with hepatomegaly, splenomegaly, anemia, bleeding tendencies, thrombocytopenia, skeletal pathologies, growth retardation, and, in severe cases, pulmonary disease. The bone manifestations include bone infarcts, avascular bone necrosis, lytic lesions, osteosclerosis, fractures due to osteopenia or osteoporosis, and rarely acute osteomyelitis. Bone pain of varying intensity, fractures, and progressive joint collapses may cause impaired mobility and performances status, and increased morbidity. Enzyme replacement therapy and substrate reduction therapy have demonstrated to have beneficial effects on bone pain, bone crises, and the extent of osteoporosis. This review article gives an overview of the clinical appearance of bone pathology in GD, the possible pathophysiological mechanisms, diagnostic approaches, and the therapeutic effects of enzyme replacement therapy, substrate reduction therapy, and bone specific therapies as evaluated in current literature.

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“…The observations are in line with other studies showing that plasma chitotriosidase activity may increase in response to a treatment interruption [11][12][13][14][15] or a switch from treatment with ERT to substrate reduction therapy (SRT). 16 Previous studies have shown velaglucerase alfa to be effective and safe in treating therapy naïve patients [6][7][8][9][10] or after a switch from stable imiglucerase dose to an equal velaglucerase dose 6,7,10 Recently, Elstein et al 10 reported a socalled 'booster-effect' with velaglucerase alfa in patients who switched from long-term imiglucerase therapy. Their study concerned a different patient population as their patients who switched had either experienced an off-treatment period or an immediate switch at equal dose from imiglucerase to velaglucerase treatment.…”

Section: Discussionmentioning

confidence: 99%

Effects of switching from a reduced dose imiglucerase to velaglucerase in type 1 Gaucher disease: clinical and biochemical outcomes

et al. 2012

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© F e r r a t a S t o r t i F o u n d a t i o n Design and Methods Referral centersIn two large European referral centers, the Academic Medical Centre in Amsterdam (The Netherlands) and Addenbrooke's Hospital in Cambridge (UK), all adult patients who switched from treatment with imiglucerase to treatment with velaglucerase during the imiglucerase shortage were included in this retrospective analysis. Dutch patients received their first infusion with velaglucerase in the hospital and then switched to home treatment, while UK patients received at least two infusions in the hospital. Home infusions were either administered by a visiting nurse or by the patients themselves. There was a substantial variation in original enzyme replacement therapy (ERT) doses between patients as a result of individualized dosing regimens in which a patient's dose was based on disease severity and individual response. Patients started velaglucerase alfa essentially at dosages equal to their original imiglucerase dose, with the exception of patient n. 9 in whom the dose was doubled.Information concerning data collection, haemoglobin level and platelet count, chitotriosidase activity, imaging and stastical analysis is available in the Online Supplementary Appendix. Results and DiscussionThirty-two adult patients switched to treatment with velaglucerase alfa: 12 patients from The Netherlands and 20 from the UK. Mean age was 52 years (range 28-72), Twenty patients were women and 17 of the 32 patients had been splenectomized.Two patients in whom the period in which the dose was reduced was less than one month are not discussed further. Both were stable during this short period of dose reduction and remained stable after switching to velaglucerase.Four patients were excluded from the analysis. In one patient, a laboratory error at the start of treatment with velaglucerase led to missing data. One patient on subjective grounds of lack of effectiveness asked to stop velaglucerase after six months of therapy; this patient returned to treatment with imiglucerase when this became available after a further six months without treatment., Finally, 2 patients suffered from complications unrelated to treatment with velaglucerase and this influenced the laboratory outcomes in such a way that effects of treatment could not be assessed. The first patient, a 60-year old woman was quadraplegic before treatment and developed severe pneumonia requiring ICU admission. The second patient, a 62-year old man, had a longstanding history of severe GD that had required a splenectomy and included multiple bone complications. A monoclonal gammopathy of undetermined significance (MGUS) had been identified at the age of 42 years and a few weeks after switching to velaglucerase, he progressed to multiple myeloma. Table 1 provides an overview of the baseline characteristics in the 26 patients who underwent analysis. Median dose prior to reduction was 47 u/kg/month (range 15-120 u/kg/month). Patients had been dose reduced ranging from 1-8.5 months (median 3.7 mon...

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Real-world clinical experience with long-term miglustat maintenance therapy in type 1 Gaucher disease: the ZAGAL project

Cited by 67 publications

References 22 publications

Gaucher Disease and Bone Manifestations

Gaucher Disease and Bone Manifestations

An overview on bone manifestations in Gaucher disease

Effects of switching from a reduced dose imiglucerase to velaglucerase in type 1 Gaucher disease: clinical and biochemical outcomes

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