Pablo Florenzano, Erik A Imel, Aliya A Khan, Zhiyi Li, Marc Vincent, Takanobu Nomura, Stanley Krolczyk, Ben Johnson, Leanne Ward
{"title":"布鲁苏单抗与口服磷酸盐和活性维生素D治疗x连锁低磷血症成人的实际有效性","authors":"Pablo Florenzano, Erik A Imel, Aliya A Khan, Zhiyi Li, Marc Vincent, Takanobu Nomura, Stanley Krolczyk, Ben Johnson, Leanne Ward","doi":"10.1093/jbmr/zjaf063","DOIUrl":null,"url":null,"abstract":"<p><p>In X-linked hypophosphatemia (XLH), PHEX gene variants lead to elevated FGF23 production, resulting in hypophosphatemia, osteomalacia, osteomalacia-related fractures, osteoarthritis, enthesopathy, spinal stenosis, and symptoms of pain, stiffness, and decreased physical function. Burosumab is an anti-FGF23 monoclonal Ab approved for XLH treatment. Randomized studies comparing oral phosphate/active vitamin D (Pi/D) to burosumab in adults are lacking. This analysis, which utilized real-world data from the prospective, Americas-based XLH Disease Monitoring Program (NCT03651505), evaluated the effectiveness of burosumab vs Pi/D, based on changes from baseline to the year 1 visit in serum phosphate, 1,25(OH)2D, PTH, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores, Patient-Reported Outcomes Measurement Information System Physical Function (PROMIS PF), and Timed Up and Go performance outcome. Two cohorts of adults with XLH who either began burosumab between baseline and the year 1 visit (n = 65) or were on Pi/D (n = 74) at study entry and did not receive burosumab were included. Inverse probability of treatment weighting was employed to adjust for potential confounding due to baseline cohort differences. At the year 1 visit, mean (SE) change from baseline was significant for burosumab vs Pi/D in serum phosphate (0.78 [0.08] vs 0.15 [0.14] mg/dL; p < .001), 1,25(OH)2D (19.41 [3.39] vs 5.49 [3.43] pg/mL; p = .011), PTH (-13.82 [5.00] vs 11.79 [8.10] pg/mL; p = .006), WOMAC pain (-7.50 [2.34] vs 4.47 [3.23]; p = .004), WOMAC physical function (-5.68 [1.96] vs 6.77 [4.85]; p = .006), and WOMAC total (-7.78 [2.06] vs 3.15 [3.37]; p = .005) scores, PROMIS PF (1.51 [0.73] vs -1.64 [1.11], p = .018), and TUG (-1.19 [0.42] vs 0.55 [0.43] s, p = .011). A trend towards improved WOMAC stiffness was observed for burosumab (-10.16 [2.85] vs -1.79 [3.68]; p = .086). In this real-world analysis of adults with XLH, burosumab treatment was associated with improved biochemical parameters, pain, physical function, and mobility compared with Pi/D.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"973-986"},"PeriodicalIF":5.9000,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12308825/pdf/","citationCount":"0","resultStr":"{\"title\":\"Real-world effectiveness of burosumab vs oral phosphate and active vitamin D in adults with X-linked hypophosphatemia.\",\"authors\":\"Pablo Florenzano, Erik A Imel, Aliya A Khan, Zhiyi Li, Marc Vincent, Takanobu Nomura, Stanley Krolczyk, Ben Johnson, Leanne Ward\",\"doi\":\"10.1093/jbmr/zjaf063\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>In X-linked hypophosphatemia (XLH), PHEX gene variants lead to elevated FGF23 production, resulting in hypophosphatemia, osteomalacia, osteomalacia-related fractures, osteoarthritis, enthesopathy, spinal stenosis, and symptoms of pain, stiffness, and decreased physical function. Burosumab is an anti-FGF23 monoclonal Ab approved for XLH treatment. Randomized studies comparing oral phosphate/active vitamin D (Pi/D) to burosumab in adults are lacking. This analysis, which utilized real-world data from the prospective, Americas-based XLH Disease Monitoring Program (NCT03651505), evaluated the effectiveness of burosumab vs Pi/D, based on changes from baseline to the year 1 visit in serum phosphate, 1,25(OH)2D, PTH, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores, Patient-Reported Outcomes Measurement Information System Physical Function (PROMIS PF), and Timed Up and Go performance outcome. Two cohorts of adults with XLH who either began burosumab between baseline and the year 1 visit (n = 65) or were on Pi/D (n = 74) at study entry and did not receive burosumab were included. Inverse probability of treatment weighting was employed to adjust for potential confounding due to baseline cohort differences. At the year 1 visit, mean (SE) change from baseline was significant for burosumab vs Pi/D in serum phosphate (0.78 [0.08] vs 0.15 [0.14] mg/dL; p < .001), 1,25(OH)2D (19.41 [3.39] vs 5.49 [3.43] pg/mL; p = .011), PTH (-13.82 [5.00] vs 11.79 [8.10] pg/mL; p = .006), WOMAC pain (-7.50 [2.34] vs 4.47 [3.23]; p = .004), WOMAC physical function (-5.68 [1.96] vs 6.77 [4.85]; p = .006), and WOMAC total (-7.78 [2.06] vs 3.15 [3.37]; p = .005) scores, PROMIS PF (1.51 [0.73] vs -1.64 [1.11], p = .018), and TUG (-1.19 [0.42] vs 0.55 [0.43] s, p = .011). A trend towards improved WOMAC stiffness was observed for burosumab (-10.16 [2.85] vs -1.79 [3.68]; p = .086). 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Real-world effectiveness of burosumab vs oral phosphate and active vitamin D in adults with X-linked hypophosphatemia.
In X-linked hypophosphatemia (XLH), PHEX gene variants lead to elevated FGF23 production, resulting in hypophosphatemia, osteomalacia, osteomalacia-related fractures, osteoarthritis, enthesopathy, spinal stenosis, and symptoms of pain, stiffness, and decreased physical function. Burosumab is an anti-FGF23 monoclonal Ab approved for XLH treatment. Randomized studies comparing oral phosphate/active vitamin D (Pi/D) to burosumab in adults are lacking. This analysis, which utilized real-world data from the prospective, Americas-based XLH Disease Monitoring Program (NCT03651505), evaluated the effectiveness of burosumab vs Pi/D, based on changes from baseline to the year 1 visit in serum phosphate, 1,25(OH)2D, PTH, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores, Patient-Reported Outcomes Measurement Information System Physical Function (PROMIS PF), and Timed Up and Go performance outcome. Two cohorts of adults with XLH who either began burosumab between baseline and the year 1 visit (n = 65) or were on Pi/D (n = 74) at study entry and did not receive burosumab were included. Inverse probability of treatment weighting was employed to adjust for potential confounding due to baseline cohort differences. At the year 1 visit, mean (SE) change from baseline was significant for burosumab vs Pi/D in serum phosphate (0.78 [0.08] vs 0.15 [0.14] mg/dL; p < .001), 1,25(OH)2D (19.41 [3.39] vs 5.49 [3.43] pg/mL; p = .011), PTH (-13.82 [5.00] vs 11.79 [8.10] pg/mL; p = .006), WOMAC pain (-7.50 [2.34] vs 4.47 [3.23]; p = .004), WOMAC physical function (-5.68 [1.96] vs 6.77 [4.85]; p = .006), and WOMAC total (-7.78 [2.06] vs 3.15 [3.37]; p = .005) scores, PROMIS PF (1.51 [0.73] vs -1.64 [1.11], p = .018), and TUG (-1.19 [0.42] vs 0.55 [0.43] s, p = .011). A trend towards improved WOMAC stiffness was observed for burosumab (-10.16 [2.85] vs -1.79 [3.68]; p = .086). In this real-world analysis of adults with XLH, burosumab treatment was associated with improved biochemical parameters, pain, physical function, and mobility compared with Pi/D.
期刊介绍:
The Journal of Bone and Mineral Research (JBMR) publishes highly impactful original manuscripts, reviews, and special articles on basic, translational and clinical investigations relevant to the musculoskeletal system and mineral metabolism. Specifically, the journal is interested in original research on the biology and physiology of skeletal tissues, interdisciplinary research spanning the musculoskeletal and other systems, including but not limited to immunology, hematology, energy metabolism, cancer biology, and neurology, and systems biology topics using large scale “-omics” approaches. The journal welcomes clinical research on the pathophysiology, treatment and prevention of osteoporosis and fractures, as well as sarcopenia, disorders of bone and mineral metabolism, and rare or genetically determined bone diseases.