TY - JOUR
T1 - Miglustat in patients with Niemann-Pick disease Type C (NP-C)
T2 - A multicenter observational retrospective cohort study
AU - Pineda, M.
AU - Wraith, J. E.
AU - Mengel, E.
AU - Sedel, F.
AU - Hwu, W. L.
AU - Rohrbach, M.
AU - Bembi, B.
AU - Walterfang, M.
AU - Korenke, G. C.
AU - Marquardt, T.
AU - Luzy, C.
AU - Giorgino, R.
AU - Patterson, M. C.
N1 - Funding Information:
This research was sponsored by Actelion Pharmaceuticals Ltd. Alpha-Plus Medical Communications provided medical writing assistance, paid for by Actelion Pharmaceuticals Ltd. Dr. Wraith is supported by the Manchester Academic Health Sciences Centre (MAHSC) and the NIHR Manchester Biomedical Research Centre. All authors read, contributed to and approved this paper, and the decision to submit this report to peer review, for publication, was reached by consensus among all listed authors.
PY - 2009/11
Y1 - 2009/11
N2 - Miglustat has been shown to stabilize disease progression in children, juveniles and adults with Niemann-Pick disease type C (NP-C), a rare genetic disorder characterized by progressive neurological deterioration. We report findings from a retrospective observational cohort study assessing the effects of miglustat on neurological disease progression in patients treated in the clinical practice setting. Data from all NP-C patients prescribed miglustat at 25 expert centers were evaluated using a disease disability scale. The scale analyzed four key parameters of neurological disease progression in NP-C (ambulation, manipulation, language, swallowing). Mean individual parameter scores and a composite score were calculated at baseline (time of diagnosis) and up to 4 follow-up visits. Overall, 66 patients were included (mean [SD] age at diagnosis, 9.7 [7.6] years, and at treatment start, 12.8 [9.5] years). The median (range) miglustat exposure was 1.46 (0.05-4.51) years. Mean annual progression was +0.11 score units/year from diagnosis to treatment start, indicating disease progression prior to therapy, and decreasing to -0.01 score units/year from treatment start to last clinic visit, indicating stabilization. Stabilization of neurological disease on miglustat was observed in all age groups, but the magnitude of the effect was greater in patients diagnosed in late childhood and in juveniles and adults. Stabilization of neurological disease was also observed in a subset of 19 patients with extended pre-treatment information. Overall, these data support previous clinical trial findings indicating clinically relevant beneficial effects of miglustat on neurological disease progression in patients with NP-C.
AB - Miglustat has been shown to stabilize disease progression in children, juveniles and adults with Niemann-Pick disease type C (NP-C), a rare genetic disorder characterized by progressive neurological deterioration. We report findings from a retrospective observational cohort study assessing the effects of miglustat on neurological disease progression in patients treated in the clinical practice setting. Data from all NP-C patients prescribed miglustat at 25 expert centers were evaluated using a disease disability scale. The scale analyzed four key parameters of neurological disease progression in NP-C (ambulation, manipulation, language, swallowing). Mean individual parameter scores and a composite score were calculated at baseline (time of diagnosis) and up to 4 follow-up visits. Overall, 66 patients were included (mean [SD] age at diagnosis, 9.7 [7.6] years, and at treatment start, 12.8 [9.5] years). The median (range) miglustat exposure was 1.46 (0.05-4.51) years. Mean annual progression was +0.11 score units/year from diagnosis to treatment start, indicating disease progression prior to therapy, and decreasing to -0.01 score units/year from treatment start to last clinic visit, indicating stabilization. Stabilization of neurological disease on miglustat was observed in all age groups, but the magnitude of the effect was greater in patients diagnosed in late childhood and in juveniles and adults. Stabilization of neurological disease was also observed in a subset of 19 patients with extended pre-treatment information. Overall, these data support previous clinical trial findings indicating clinically relevant beneficial effects of miglustat on neurological disease progression in patients with NP-C.
KW - Cohort
KW - Disability
KW - Miglustat
KW - Niemann-Pick disease Type C
KW - Observational
KW - Progression
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U2 - 10.1016/j.ymgme.2009.07.003
DO - 10.1016/j.ymgme.2009.07.003
M3 - Article
C2 - 19656703
AN - SCOPUS:70349748397
SN - 1096-7192
VL - 98
SP - 243
EP - 249
JO - Molecular genetics and metabolism
JF - Molecular genetics and metabolism
IS - 3
ER -