12589 Two Systematic Reviews Of Treatment Efficacy On Patient Important Outcomes In Adult X-linked Hypophosphatemia
Bibliographic record
Abstract
Abstract Disclosure: D.S. Ali: None. R. Mirza: None. F. Alsarraf: None. S. Hussein: None. N. Appelman-Dijkstra: Consulting Fee; Self; Amgen Inc, Kyowa Kirin, UCB. Grant Recipient; Self; Kyowa Kirin. S. Beck-Nielsen: Consulting Fee; Self; Kyowa Kirin, Inozymes, Novo Nordisk. Grant Recipient; Self; Kyowa Kirin. Speaker; Self; Kyowa Kirin. M. Biosse-Duplan: Advisory Board Member; Self; Alexion Pharmaceuticals, Inc.. Grant Recipient; Self; Kyowa Kirin. Speaker; Self; Kyowa Kirin, Alexion Pharmaceuticals, Inc. M. Brandi: Consulting Fee; Self; Alexion Pharmaceuticals, Inc., Aboca, Amolyt, Bruno Farmaceutici, Calcilytix, Kyowa Kirin. Speaker; Self; Alexion Pharmaceuticals, Inc., Amgen Inc, Eli Lilly & Company, Takeda, Kyowa Kirin. C. Chaussain: Grant Recipient; Self; Kyowa Kirin. M. Cohen-Solal: Grant Recipient; Self; Kyowa Kirin. Speaker; Self; Kyowa Kirin. R.K. Crowley: Advisory Board Member; Self; UCB, Amgen Inc. Consulting Fee; Self; Kyowa Kirin. Speaker; Self; Kyowa Kirin. K. Dandurand: Speaker; Self; Amgen Inc, Kyowa Kirin. P.F. Florenzano: None. S. Fukumoto: Consulting Fee; Self; Kyowa Kirin. C. Gagnon: Grant Recipient; Self; Takeda, Ascendis Pharma. P. Goodyer: None. C. Grasemann: Speaker; Self; Kyowa Kirin. E.A. Imel: Consulting Fee; Self; Ultragenyx, Kyowa Kirin, Inozyme. Grant Recipient; Self; Ultragenyx, Kyowa Kirin, Amgen Inc. S.M. Jan De Beur: Consulting Fee; Self; Kyowa Kirin, Ultragenyx. E.M. Lewiecki: Consulting Fee; Self; Amgen Inc. Research Investigator; Self; Amgen Inc, Ultragenyx. Speaker; Self; Amgen Inc, Ascendis. E. Morgante: None. L. Ward: Other; Self; Tier 1 (Senior) Research Chair in Pediatric Bone Disorders from the University of Ottawa and the Children’s Hospital of Eastern Ontario Research Institute. A.A. Khan: Advisory Board Member; Self; Amgen Inc, Takeda, Alexion, Ascendis. Grant Recipient; Self; Takeda, Ascendis, Amolyt, Calcilytix. G. Guyatt: None. Objective: Our objective was to examine the highest certainty evidence addressing the management of X-linked hypophosphatemia in adults, aiming to inform treatment recommendations. Eligibility criteria: We searched Embase, MEDLINE, Web of Science, and Cochrane from inception to March 2023 and included RCTs and observational studies enrolling individuals ≥ 18 years diagnosed with XLH on clinical grounds or with a confirmed pathogenic variant in PHEX. Manuscripts evaluating the effectiveness of burosumab compared to either no treatment or conventional therapy (phosphate salts and active vitamin D) or evaluating conventional therapy compared to no treatment were selected. Methods: Two reviewers independently determined eligibility, conducted data extraction, and assessed the risk of bias (RoB). GRADE was used to assess certainty of evidence. Results: After removing duplicates from 7,043 citations, we assessed 254 full texts. Of those, one RCT proved eligible. The RCT of burosumab versus no treatment was at low RoB with certainty of evidence on individual outcomes ranging from high to very low. Burosumab probably improves pain inferred from fracture and pseudofracture healing (moderate certainty); however, burosumab probably has little or no impact on direct pain measures (moderate certainty). While burosumab may reduce the need for parathyroidectomy, indicated by lowered PTH levels (low certainty), it has little or no impact on fatigue (high certainty), stiffness (moderate certainty), and mobility (low certainty) over 24 weeks. Burosumab may also increase dental abscesses (low certainty). No formal comparisons of burosumab and conventional therapy exist; therefore, our low certainty evidence inferences regarding burosumab versus conventional therapy were based on indirect evidence from comparisons of burosumab versus no treatment and from conventional therapy versus no treatment. Observational studies proved at high RoB providing very low certainty of evidence regarding the impact of conventional therapy versus no treatment. This evidence pertained to the reduction in the risk of parathyroidectomy, as well as the reduction in the burden of symptoms caused by chronic hypophosphatemia. Conclusion: Burosumab when compared to no treatment may improve pain through fracture healing and may reduce the need for parathyroidectomy, but it could also increase the risk of dental abscess. However, when using direct measures of pain and function, burosumab demonstrated probably little or no impact on pain and stiffness, little or no impact on fatigue, and may have had little to no impact on mobility. Very low certainty exists regarding conventional therapy versus no treatment in adults. Overall, our review highlights the need for more data to better understand the long-term impact of burosumab and conventional therapy on patient-important outcomes. Presentation: 6/2/2024
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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 | 0.012 | 0.076 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.008 | 0.014 |
| Bibliometrics | 0.007 | 0.007 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.003 | 0.002 |
| Open science | 0.001 | 0.002 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.014 | 0.001 |
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".