Hypophosphatasia: presentation and response to asfotase alfa.

Autor: Alsarraf F; Division of Endocrinology and Metabolism, McMaster University, Hamilton, Ontario, Canada. Dr.farahaalsarraf@gmail.com., Ali DS; Division of Endocrinology and Metabolism, McMaster University, Hamilton, Ontario, Canada., Almonaei K; Department of Endocrinology and Diabetes, Diabetes Treatment Center, Prince Sultan Military Medical City, Riyadh, Saudi Arabia., Al-Alwani H; Department of Medicine, University of Jeddah, Jeddah, Saudi Arabia., Khan AA; Division of Endocrinology and Metabolism, McMaster University, Hamilton, Ontario, Canada., Brandi ML; F.I.R.M.O. Italian Foundation for the Research on Bone Diseases, Florence, Italy.; Donatello Bone Clinic, Villa Donatello Hospital, Florence, Italy.
Jazyk: angličtina
Zdroj: Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA [Osteoporos Int] 2024 Apr; Vol. 35 (4), pp. 717-725. Date of Electronic Publication: 2023 Nov 23.
DOI: 10.1007/s00198-023-06943-z
Abstrakt: Hypophosphatasia (HPP) is a rare bone disease with limited scientific evidence on the tolerability and safety of its novel treatment, Asfotase Alfa (AA). We report 7 HPP patients' heterogenous presentations and the significant improvement in various clinical outcomes attained with AA shedding light on this highly effective and safe therapy.
Introduction: Hypophosphatasia (HPP) is a rare inherited metabolic bone disorder characterized by a deficiency in the tissue non-specific alkaline phosphatase (TNSALP) due to loss of function mutation in the ALPL gene. HPP is associated with impaired skeletal mineralization due to elevations in inorganic pyrophosphate and altered phosphate : pyrophosphate ratio. Asfotase alfa (AA) "enzyme replacement" was approved for treatment of HPP in 2015. We present 7 patients with HPP, 5 with pediatric-onset, and 2 with adult-onset, who have been treated with AA and describe the efficacy and safety in these patients.
Methods: 7 patients (4 females, 3 males) aged 19-68 years with HPP were included in this study. Diagnosis of HPP was confirmed by DNA analysis. AA was administered in doses of 6mg/kg/week with a mean follow-up of 6 months (SD= 5).
Results: Subjective improvement in muscle strength, muscle pain, walking ability, and walking distance with a reduction in the use of gait aids was seen "with AA in HPP patients." Muscle strength and pain improved by up to 70% from baseline as quantified subjectively by patients. Walking distance improved by up to 100%. Patients also reported improved cognition, mood, and energy levels, with up to 90% improvement in mood and 75% improvement in energy levels. 4 out of 6 patients first noted clinical signs of improvement after 3 months of being on therapy. 1 out of the 7 patients sustained a toe fracture 10 months from being on AA. AA was well-tolerated with injection site reactions being the most reported adverse effect.
Conclusion: HPP treatment with AA in individuals with both pediatric and adult-onset forms resulted in significant subjective improvement in musculoskeletal and cognitive manifestations in addition to patients' quality of life. The drug was well tolerated in 6 patients. 1 patient discontinued therapy because of minor adverse effects with myalgias.
(© 2023. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)
Databáze: MEDLINE
Externí odkaz: