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- Nilsson, Ola, 1970-, et al.
(författare)
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Burosumab Improved Rickets, Phosphate Metabolism, and Clinical Outcomes Compared to Conventional Therapy in Children with X-Linked Hypophosphatemia (XLH) - A Randomized Controlled Phase 3 Study
- 2018
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Ingår i: Hormone Research in Paediatrics. - : S. Karger. - 1663-2818 .- 1663-2826. ; 90:Suppl.1, s. 57-58
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- In children with XLH, high circulating levels of FGF23 cause hypophosphatemia with consequent rickets, skeletal deformities, and growth impairment. Conventional therapy consists of multiple daily doses of oral phosphate and active vitamin D (Pi/D). Burosumab is a fully human monoclonal antibody against FGF23 indicated for the treatment of XLH.In the active-control study CL301 (NCT02915705), 61 children with XLH (1-12 years old) were randomized (1:1) to receive subcutaneous burosumab starting at 0.8 mg/kg every 2 weeks (Q2W) or Pi/D as prescribed by investigators. Eligibility criteria included a Total Rickets Severity Score (RSS) ≥2.0 and prior receipt of Pi/D. The primary endpoint was healing of rickets at Week 40 assessed by radiologists blinded to treatment using the Radiographic Global Impression of Change (RGI-C).At Week 40, burosumab significantly improved rickets compared with Pi/D (RGI-C global score least squares [LS] mean ± SE: +1.92 ± 0.11 vs +0.77 ± 0.11; p<0.0001). More subjects in the burosumab group had substantial healing (RGI-C ≥+2.0) at Week 40, compared with the Pi/D group (21/29, 72% vs 2/32, 6%; odds ratio of 39.1, p<0.0001). Additional evidence for improvement of rickets included decreased Total RSS (LS mean ± SE change, burosumab vs Pi/D: -2.04 ± 0.145 vs -0.71 ± 0.138; p<0.0001), decreased alkaline phosphatase (-131 ± 13 vs -35 ± 19; p<0.0001), and improved RGI-C lower limb deformity score (+0.62 ± 0.12 vs +0.21 ± 0.12; p=0.020). At Week 40, increases in serum phosphorous (p<0.0001) and TmP/GFR (p<0.0001) were significantly greater with burosumab compared with Pi/D. Standing height Z-score increased in both treatment groups from baseline to Week 40 with an LS mean change of +0.15 (95% CI: 0.05, 0.25) for burosumab and +0.08 (-0.02, 0.19) for Pi/D. Percent predicted distance walked in six minutes increased with burosumab (Baseline to Week 40: 62% to 72%) and was unchanged with Pi/D (76% to 75%). Pre-defined adverse events (AEs) of interest, including hypersensitivity and injection site reaction, were higher in the burosumab group, but were mild to moderate in severity overall, with no discontinuations. There were 4 serious AEs (3 burosumab, 1 Pi/D); none were treatment-related and all resolved.In this randomized Phase 3 clinical trial, burosumab Q2W re-sulted in significantly greater improvements in rickets and phosphate metabolism compared with conventional therapy in 1-12 year-old children with XLH.
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- Padidela, Raja, et al.
(författare)
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Patient-reported outcomes from a randomized open-label phase 3 trial comparing burosumab versus conventional therapy in children with X-linked hypophosphatemia : results from the 24-week treatment extension period
- 2022
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Ingår i: Hormone Research in Paediatrics. - : S. Karger. - 1663-2818 .- 1663-2826. ; 95:Suppl. 2, s. 29-30
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- In a randomized open-label phase 3 trial in 62 children (1–12 years) with X-linked hypophosphatemia (XLH) (NCT 02915705), switching from conventional therapy (oral phosphate plus active vitamin D) to burosumab, a monoclonal antibody targeting fibroblast growth factor 23, significantly improved serum phosphate concentration, rickets, lower-extremity deformities, growth, mobility, and patient-reported outcomes (PROs) at 64 weeks. Children in Europe, USA, Canada, and Australia who completed 64 weeks’ treatment could continue to receive burosumab in the extension period (burosumab continuation group) or cross over from conventional therapy to burosumab (crossover group) to 124 weeks. A Patient-Reported Outcomes Measurement Information System (PROMIS) questionnaire was used in children aged ≥5 years to measure Pain Interference, Physical Function Mobility, and Fatigue; health-related quality of life was measured using the SF-10 Health Survey for Children (n=35). Here, we describe changes in PROs from baseline to weeks 64 and 88, and report whether the 3-point minimal important difference (MID) was reached for PROMIS domains (Thissen et al., 2016; PMID 26118768). The mean change from baseline exceeded the MID for Pain Interference at weeks 64 and 88 and for Fatigue at week 64 in the burosumab continuation group, and for Pain Interference and Fatigue at week 88 in the crossover group. Similar improvements in SF-10 Physical Health were seen baseline to week 64 in the burosumab continuation group, and week 64 to 88 in the cross-over group. SF-10 Psychosocial Health changed little in either group at the two timepoints.Treatment with burosumab improved Pain Interference and Fatigue beyond the MID in children with XLH who switched from conventional therapy to receive 24 weeks of burosumab. Improvements were also maintained in children who received an additional 24 weeks’ burosumab treatment.
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- Simmons, D., et al.
(författare)
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Treatment of Gestational Diabetes Mellitus Diagnosed Early in Pregnancy
- 2023
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Ingår i: Obstetrical and Gynecological Survey. - : Lippincott Williams & Wilkins. - 0029-7828 .- 1533-9866. ; 78:11, s. 636-637
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- (Abstracted from N Engl J Med 2023;388(23):2132-2144) Gestational diabetes mellitus is a common pregnancy complication. It is associated with adverse outcomes, including preeclampsia, obstetrical intervention, large-for-gestational-age neonates, shoulder dystocia, birth trauma, and neonatal hypoglycemia. Cohort studies have found that women with hyperglycemia before 20 weeks of gestation are more likely to experience accelerated fetal growth by 24 to 28 weeks than those diagnosed with GDM later in pregnancy.
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