Therapeutic goals in the treatment of Gaucher disease

Pastores, Gregory M.; Weinreb, Neal J.; Aerts, Johannes M. F. G.; Andria, Generoso; Cox, Timothy M.; Giralt, Manuel; Grabowski, Gregory A.; Mistry, Pramod K.; Tylki‐Szymańska, Anna

doi:10.1053/j.seminhematol.2004.07.009

Cited by 378 publications

(417 citation statements)

References 52 publications

Supporting

Mentioning

356

Contrasting

Unclassified

Order By: Relevance

“…The therapeutic goal for liver volume reduction of 1 year 10 was seen in four (40%) patients at 6 months, and normalization of hepatomegaly was observed by 45 months among all seven completers whose assessments were consistent with hepatomegaly at baseline. The therapeutic goal of 1 year for reduction of spleen volume 10 was seen at 6 months in nine (90%) patients. Although no patient exhibited normalization in spleen volume, a marked reduction (>74%) from baseline splenomegaly was nevertheless observed among all completers.…”

Section: Resultsmentioning

confidence: 91%

“…All patients achieved normal hemoglobin levels within 24 months of initiation of therapy while the therapeutic goal for anemia at 1 year 10 was achieved in all patients by 9 months. Although all patients who entered the phase I/II trial exhibited moderate to severe thrombocytopenia at baseline, all eight completers achieved platelet counts in the nonpathologic range (five achieved near‐normal values, and three achieved normal values at their final assessment).…”

Section: Resultsmentioning

confidence: 95%

“…Although all patients who entered the phase I/II trial exhibited moderate to severe thrombocytopenia at baseline, all eight completers achieved platelet counts in the nonpathologic range (five achieved near‐normal values, and three achieved normal values at their final assessment). The 1‐year therapeutic goal for increased platelet counts 10 was achieved by three (30%) patients at 6 months. The therapeutic goal for liver volume reduction of 1 year 10 was seen in four (40%) patients at 6 months, and normalization of hepatomegaly was observed by 45 months among all seven completers whose assessments were consistent with hepatomegaly at baseline.…”

Section: Resultsmentioning

confidence: 99%

“…The 1‐year therapeutic goal for increased platelet counts 10 was achieved by three (30%) patients at 6 months. The therapeutic goal for liver volume reduction of 1 year 10 was seen in four (40%) patients at 6 months, and normalization of hepatomegaly was observed by 45 months among all seven completers whose assessments were consistent with hepatomegaly at baseline. The therapeutic goal of 1 year for reduction of spleen volume 10 was seen at 6 months in nine (90%) patients.…”

Section: Resultsmentioning

confidence: 99%

“…In the phase I/II trial, the dose administered to patients was 60 U/kg body weight over 60 min EOW. In the extension study, a step‐wise dose reduction from 60 to 30 U/kg was implemented after a cumulative study period of 15 to 18 months (after the phase I/II trial and 6 to 9 months in the extension study) in patients in whom at least two of four therapeutic goals were achieved as previously described 10. Patients enrolled in the extension study who did not experience a drug‐related serious AE or an infusion‐related AE were eligible to receive home‐based infusions under the supervision of a healthcare professional.…”

Section: Methodsmentioning

confidence: 99%

See 4 more Smart Citations

Seven‐year safety and efficacy with velaglucerase alfa for treatment‐naïve adult patients with type 1 Gaucher disease

et al. 2015

View full text Add to dashboard Cite

Velaglucerase alfa is a human β‐glucocerebrosidase approved for Gaucher disease type 1 (GD1) treatment. This report summarizes the 7‐year experience of the now‐completed phase I/II and extension studies of adult GD1 patients who received velaglucerase alfa. Ten patients who completed the 9‐month, phase I/II study entered the extension trial TKT025EXT, of which eight completed this study. Doses were reduced after a cumulative treatment period of 15 to 18 months. Although all patients experienced ≥1 adverse event, no patient withdrew due to a drug‐related adverse event or required premedication. No patient developed anti‐drug antibodies, compliance remained high (median 98%), and seven of eight eligible patients transitioned to home infusions under supervision by healthcare professionals. Statistically significant improvements were observed for efficacy parameters: mean percentage changes from baseline (95% confidence intervals) were 18% (12%, 24%) for hemoglobin concentration, 115% (66%, 164%) for platelet counts, and −42% (−53%, −31%) and −78% (−94%, −62%) for liver and spleen volumes, respectively. Improvements were also observed for secondary endpoints chitotriosidase and CCL18 levels and exploratory endpoints (bone mineral density [BMD], bone marrow burden [BMB] scores). Normalization to near‐normalization of individuals' hemoglobin concentrations, platelet counts, liver volumes, and BMB scores was observed, and there were marked improvements in spleen volumes, biomarkers, and BMD. TKT025EXT represents the longest, prospective clinical trial for GD1 treatment to date and suggests that, despite dose reduction within 18 months of initiating therapy, velaglucerase alfa was generally well tolerated and was associated with marked improvement, including near normalization and/or normalization of key GD1 disease parameters. Am. J. Hematol. 90:577–583, 2015. © 2015 The Authors. American Journal of Hematology published by Wiley Periodicals, Inc.

show abstract

Section: Resultsmentioning

confidence: 91%

Section: Resultsmentioning

confidence: 95%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 3 more Smart Citations

Seven‐year safety and efficacy with velaglucerase alfa for treatment‐naïve adult patients with type 1 Gaucher disease

et al. 2015

View full text Add to dashboard Cite

show abstract

The Clinical and Demographic Characteristics of Nonneuronopathic Gaucher Disease in 887 Children at Diagnosis

Kaplan

Andersson²,

Kacena³

et al. 2006

Arch Pediatr Adolesc Med

168

123

View full text Add to dashboard Cite

Nonneuronopathic GD commonly manifests in childhood and affects many ethnic groups. The high prevalence of rare mutations may be associated with earlier onset and/or more severe disease. Increased awareness of the clinical and demographic characteristics of nonneuronopathic GD in children may improve early recognition of this treatable lysosomal storage disorder, decrease morbidity, and prevent irreversible sequelae.

show abstract