TY - JOUR
T1 - Safety and efficacy of treatment with asfotase alfa in patients with hypophosphatasia
T2 - Results from a Japanese clinical trial
AU - Kitaoka, Taichi
AU - Tajima, Toshihiro
AU - Nagasaki, Keisuke
AU - Kikuchi, Toru
AU - Yamamoto, Katsusuke
AU - Michigami, Toshimi
AU - Okada, Satoshi
AU - Fujiwara, Ikuma
AU - Kokaji, Masayuki
AU - Mochizuki, Hiroshi
AU - Ogata, Tsutomu
AU - Tatebayashi, Koji
AU - Watanabe, Atsushi
AU - Yatsuga, Shuichi
AU - Kubota, Takuo
AU - Ozono, Keiichi
N1 - Funding Information:
The authors thank Kanako Tachikawa (Department of Bone and Mineral Research, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka, Japan) for gene mutation analysis. We thank all the study participants and staff at our collaborating centres.
Publisher Copyright:
© 2017 John Wiley & Sons Ltd
PY - 2017/7
Y1 - 2017/7
N2 - 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.
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.
KW - alkaline phosphatase
KW - asfotase alfa
KW - convulsion
KW - enzyme replacement therapy
KW - hypocalcaemia
KW - hypophosphatasia
UR - http://www.scopus.com/inward/record.url?scp=85018743376&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85018743376&partnerID=8YFLogxK
U2 - 10.1111/cen.13343
DO - 10.1111/cen.13343
M3 - Article
C2 - 28374482
AN - SCOPUS:85018743376
VL - 87
SP - 10
EP - 19
JO - Clinical Endocrinology
JF - Clinical Endocrinology
SN - 0300-0664
IS - 1
ER -
