PMID- 28374482
OWN - NLM
STAT- MEDLINE
DCOM- 20180319
LR  - 20220408
IS  - 1365-2265 (Electronic)
IS  - 0300-0664 (Linking)
VI  - 87
IP  - 1
DP  - 2017 Jul
TI  - Safety and efficacy of treatment with asfotase alfa in patients with 
      hypophosphatasia: Results from a Japanese clinical trial.
PG  - 10-19
LID - 10.1111/cen.13343 [doi]
AB  - OBJECTIVE: Hypophosphatasia (HPP) is a rare skeletal disease characterized by 
      hypomineralization and low alkaline phosphatase activity. Asfotase alfa (AA) has 
      been recently developed to treat HPP complications. This study evaluated its 
      safety and efficacy in Japan. DESIGN: Open-label, multicentre, prospective trial. 
      Patients were enrolled in 11 hospitals from June 2014 to July 2015. PATIENTS: 
      Thirteen patients (9 females, 4 males) ages 0 days to 34 years at baseline were 
      enrolled and treated with AA (2 mg/kg three times weekly subcutaneously in all 
      but one patient). All had ALPL gene mutations. HPP forms were perinatal (n=6), 
      infantile (n=5), childhood (n=1) and adult (n=1). MEASUREMENTS: Safety determined 
      from adverse events (AEs) and laboratory data was the primary outcome measure. 
      Efficacy was assessed as a secondary outcome measure from overall survival, 
      respiratory status, rickets severity and gross motor development. RESULTS: 
      Injection site reactions were the most frequent AEs. Serious AEs possibly related 
      to treatment were convulsion and hypocalcaemia observed in a patient with the 
      perinatal form. In addition, hypercalcaemia and/or hyperphosphatemia was observed 
      in three patients with the infantile form and a low-calcium and/or low-phosphate 
      formula was given to these patients. With respect to efficacy, all patients 
      survived and the radiographic findings, developmental milestones and respiratory 
      function improved. CONCLUSION: Asfotase alfa therapy improved skeletal, 
      respiratory and physical symptoms with a few serious AEs in patients with HPP. 
      Our results add support to the safety and efficacy of AA therapy for HPP 
      patients.
CI  - (c) 2017 John Wiley & Sons Ltd.
FAU - Kitaoka, Taichi
AU  - Kitaoka T
AUID- ORCID: 0000-0002-3531-884X
AD  - Department of Pediatrics, Osaka University Graduate School of Medicine, Osaka, 
      Japan.
FAU - Tajima, Toshihiro
AU  - Tajima T
AD  - Department of Pediatrics, Hokkaido University School of Medicine, Sapporo, Japan.
FAU - Nagasaki, Keisuke
AU  - Nagasaki K
AD  - Division of Pediatrics, Department of Homeostatic Regulation and Development, 
      Niigata University Graduate School of Medical and Dental Sciences, Niigata, 
      Japan.
FAU - Kikuchi, Toru
AU  - Kikuchi T
AD  - Division of Pediatrics, Department of Homeostatic Regulation and Development, 
      Niigata University Graduate School of Medical and Dental Sciences, Niigata, 
      Japan.
FAU - Yamamoto, Katsusuke
AU  - Yamamoto K
AD  - Department of Pediatric Nephrology and Metabolism, Osaka Medical Center and 
      Research Institute for Maternal and Child Health, Osaka, Japan.
FAU - Michigami, Toshimi
AU  - Michigami T
AD  - Department of Bone and Mineral Research, Osaka Medical Center and Research 
      Institute for Maternal and Child Health, Osaka, Japan.
FAU - Okada, Satoshi
AU  - Okada S
AD  - Department of Pediatrics, Hiroshima University Graduate School of Biomedical & 
      Health Sciences, Hiroshima, Japan.
FAU - Fujiwara, Ikuma
AU  - Fujiwara I
AD  - Department of Pediatrics, Tohoku University School of Medicine, Miyagi, Japan.
FAU - Kokaji, Masayuki
AU  - Kokaji M
AD  - Department of Pediatrics, Showa General Hospital, Tokyo, Japan.
FAU - Mochizuki, Hiroshi
AU  - Mochizuki H
AD  - Division of Endocrinology and Metabolism, Saitama Children's Medical Center, 
      Saitama, Japan.
FAU - Ogata, Tsutomu
AU  - Ogata T
AD  - Department of Pediatrics, Hamamatsu University School of Medicine, Hamamatsu, 
      Japan.
FAU - Tatebayashi, Koji
AU  - Tatebayashi K
AD  - Department of Pediatrics, Nagara Medical Center, Gifu, Japan.
FAU - Watanabe, Atsushi
AU  - Watanabe A
AD  - Division of Clinical Genetics, Nippon Medical School Hospital, Tokyo, Japan.
FAU - Yatsuga, Shuichi
AU  - Yatsuga S
AD  - Department of Pediatrics and Child Health, Kurume University School of Medicine, 
      Fukuoka, Japan.
FAU - Kubota, Takuo
AU  - Kubota T
AD  - Department of Pediatrics, Osaka University Graduate School of Medicine, Osaka, 
      Japan.
FAU - Ozono, Keiichi
AU  - Ozono K
AD  - Department of Pediatrics, Osaka University Graduate School of Medicine, Osaka, 
      Japan.
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
PT  - Multicenter Study
DEP - 20170502
PL  - England
TA  - Clin Endocrinol (Oxf)
JT  - Clinical endocrinology
JID - 0346653
RN  - 0 (Immunoglobulin G)
RN  - 0 (Recombinant Fusion Proteins)
RN  - EC 3.1.3.1 (ALPL protein, human)
RN  - EC 3.1.3.1 (Alkaline Phosphatase)
RN  - SY7Q814VUP (Calcium)
RN  - Z633861EIM (asfotase alfa)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Alkaline Phosphatase/*administration & dosage/adverse 
      effects/*genetics/therapeutic use
MH  - Calcium/blood
MH  - Child
MH  - Child, Preschool
MH  - Female
MH  - Humans
MH  - Hyperphosphatemia/chemically induced
MH  - Hypophosphatasia/*drug therapy
MH  - Immunoglobulin G/*administration & dosage/adverse effects/therapeutic use
MH  - Infant
MH  - Infant, Newborn
MH  - Japan
MH  - Male
MH  - Mutation
MH  - Recombinant Fusion Proteins/*administration & dosage/adverse effects/therapeutic 
      use
MH  - Survival Rate
MH  - Treatment Outcome
MH  - Young Adult
OTO - NOTNLM
OT  - alkaline phosphatase
OT  - asfotase alfa
OT  - convulsion
OT  - enzyme replacement therapy
OT  - hypocalcaemia
OT  - hypophosphatasia
EDAT- 2017/04/05 06:00
MHDA- 2018/03/20 06:00
CRDT- 2017/04/05 06:00
PHST- 2017/04/05 06:00 [pubmed]
PHST- 2018/03/20 06:00 [medline]
PHST- 2017/04/05 06:00 [entrez]
AID - 10.1111/cen.13343 [doi]
PST - ppublish
SO  - Clin Endocrinol (Oxf). 2017 Jul;87(1):10-19. doi: 10.1111/cen.13343. Epub 2017 
      May 2.