THU460 A Case Series Of Hypophosphatasia: Presentation And Response To Asfotase Alfa
Bibliographic record
Abstract
Abstract Disclosure: F. Alsarraf: None. D.S. Ali: None. K. Almonaei: None. H. Al-Alwani: None. M. Brandi: Consulting Fee; Self; Aboca, Alexion Pharmaceuticals, Inc., Amolyt, Bruno Farmaceutici, Calcilytix, Kyowa Kirin, UCB. Grant Recipient; Self; Abiogen, Alexion Pharmaceuticals, Inc., Amgen Inc, Bruno Farmaceutici, Echolight, Eli Lilly & Company, Kyowa Kirin, SPA, Theramex, UCB. Speaker; Self; Abiogen, Alexion Pharmaceuticals, Inc., Amgen Inc, Bruno Farmaceutici, Calcilytix, Echolight, Eli Lilly & Company, Kyowa Kirin, SPA, Theramex, UCB. A.A. Khan: Advisory Board Member; Self; Amgen Inc, Amolyt, Takeda. Consulting Fee; Self; Amgen Inc. Grant Recipient; Self; Alexion Pharmaceuticals, Inc., Amgen Inc, Ascendis, Chugai, Radius Health, Inc, Takeda, Ultragenyx. Research Investigator; Self; Amgen Inc, Radius Health, Inc. Speaker; Self; Alexion Pharmaceuticals, Inc., Amgen Inc. 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) was approved for treatment of HPP in 2015. We present a case series of 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. Case presentation: 7 patients (4 females, 3 males) aged 19-68 years with HPP were included in this case series. 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). Management outcome: Improvement in muscle strength, muscle pain, walking ability and walking distance with a reduction in the use of gait aids was seen. 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 commonly reported adverse effect. Discussion: HPP treatment with AA in individuals with both pediatric and adult-onset forms resulted in significant improvement in musculoskeletal and cognitive manifestations in addition to patients’ quality of life. It was well tolerated in 6 patients. 1 patient discontinued therapy because of minor adverse effects with myalgias. Presentation: Thursday, June 15, 2023
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.003 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.002 |
| Bibliometrics | 0.002 | 0.002 |
| Science and technology studies | 0.002 | 0.001 |
| Scholarly communication | 0.002 | 0.002 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.005 | 0.003 |
| Insufficient payload (model declined to judge) | 0.005 | 0.002 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".