Ashrafzadeh‐Kian, Susan

AbstractObjectiveTo investigate the effect of CRYSVITA® (burosumab‐twza) on FGF23 measurements in an intact and a C‐terminal immunoassay.MethodsAn intact serum FGF23 (MedFrontier) and a C‐terminal plasma FGF23 assay (Immutopics) were used. Serum/plasma pools were spiked to span the burosumab therapeutic range (1.4–11.3 μg/ml) and FGF23 recovery was assessed. Patient serum and plasma samples obtained pre and post‐burosumab treatment were evaluated on both assays and compared with corresponding phosphorus measurementsResultsSpiking burosumab (1.4–11.3 μg/ml) into sample pools resulted in a dose‐dependent negative analytical interference on intact FGF23 measurements and no significant interference for C‐terminal FGF23 measurements. However, more than a 500‐fold median increase (post‐ vs. pre‐burosumab administration) in in vivo FGF23 concentrations were observed by both assays.ConclusionsTherapeutic concentrations of burosumab result in a negative analytical interference of the intact, but not the C‐terminal FGF23 immunoassay. Despite this in vitro analytical interference in the intact assay, relatively large elevations of both intact FGF23 and C‐terminal FGF23 measurements were observed in vivo following burosumab administration. Following burosumab administration, FGF23 measurements must be interpreted within the clinical context of the patient and other relevant biomarker results.SummaryThis article describes a negative analytical interference by burosumab in an intact FGF23 immunoassay. The recovery of C‐terminal FGF23 is not significantly affected by the presence of burosumab. In vivo, both assays demonstrate extreme FGF23 elevations in the presence of the drug. Furthermore, the measurement of FGF23 blocked by burosumab is not clinically useful regarding hypophosphataemia.

Abstract Objectives Assessment of surgical outcome in acromegaly is typically recommended at 3 to 6 months following surgery. The purpose of this study was to determine if insulin-like growth factor 1 (IGF-1) concentrations at 6 weeks were equally predictive of surgical outcomes compared with IGF-1 concentrations at 3 to 6 months postoperatively applying newer IGF-1 assays. Methods Retrospective review of patients with newly diagnosed acromegaly who had surgery between 2013 and 2020 and had postoperative IGF-1 measured by 6 weeks and 3 to 6 months. Results At 6 weeks, 20 (35%) of the total 57 had normal IGF-1 and became abnormal in 1 at 3 to 6 months, whereas 37 (65%) of 57 had abnormal IGF-1 concentrations at 6 weeks, which normalized in 1 patient by 3 to 6 months. In patients who changed clinical status, IGF-1 at 6 weeks was within ±0.1-fold of normal. Although a difference was seen between median IGF-1 concentrations (286 vs 267 ng/mL, P = .009) at 6 weeks and 3 to 6 months, the mean reduction was small (–19.9 ng/mL). Conclusions Compared with 3 to 6 months, use of IGF-1 at 6 weeks was associated with a change in clinical status in 3.5% of patients. Therefore, in most patients, IGF-1 at 6 weeks can be used to assess clinical outcome via newer assays.

Abstract Introduction Measurement of amyloid beta (Aβ40 and Aβ42) and tau (phosphorylated tau [p‐tau] and total tau [t‐tau]) in cerebrospinal fluid (CSF) can be utilized to differentiate clinical and preclinical Alzheimer's disease dementia (AD) from other neurodegenerative processes. Methods CSF biomarkers were measured in 150 participants from the Mayo Clinic Study of Aging and the Alzheimer's Disease Research Center. P‐tau/Aβ42 (Roche Elecsys, Fujirebio LUMIPULSE) and Aβ42/40 (Fujirebio LUMIPULSE) ratios were compared to one another and to amyloid positron emission tomography (PET) classification. Results Strong correlation was observed between LUMIPULSE p‐tau/Aβ42 and Aβ42/40, as well as Elecsys and LUMIPULSE p‐tau/Aβ42 and Aβ42/40 (Spearman's ρ = –0.827, –0.858, and 0.960, respectively). Concordance between LUMIPULSE p‐tau/Aβ42 and Aβ42/40 was 96% and between Elecsys p‐tau/Aβ42 and both LUMIPULSE ratios was 97%. All ratios had > 94% overall, positive, and negative percent agreement with amyloid PET classification. Discussion These data suggest that p‐tau/Aβ42 and Aβ42/40 ratios provide similar clinical information in the assessment of amyloid pathology.

Abstract Background: Measurement of parathyroid hormone related peptide (PTHrP) is helpful in the diagnosis and clinical management of patients suspected of humoral hypercalcemia of malignancy (HHM). In these patients uncontrolled release of PTHrP by tumor cells is responsible for the hypercalcemia and PTH concentrations are typically suppressed. Objective: Develop a sensitive and specific assay for quantitation of PTHrP in plasma. Method: Calibrators (PTHrP 1-86) and samples (50uL) were incubated with an anti-PTHrP goat polyclonal acridinium ester labeled antibody. Complexes were transferred and incubated in a microplate coated with an anti-PTHrP polyclonal rabbit antibody. After washing, the acridinium ester generated signal, which is directly proportional to the amount of PTHrP in sample, was quantified. Results: In this assay PTHrp was stable for 24 hours ambient, 3 days refrigerated, 34 days frozen and through 3 freeze/thaws. Intra and inter-assay imprecision in EDTA plasma (~0.16-35.0 pmol/L) ranged from 2.2-8.6% and 5-15%, respectively. The limit of detection was 0.04 pmol/L and the limit of quantitation was 0.16 pmol/L (15% CV). The analytical measuring range was 0.39-50.5 pmol/L (slope of 1.07 and r2 of 0.99). Average spike recovery was 98% (range 85-108%). The assay was not affected by hemoglobin of ≤500 mg/dL, triglycerides of ≤2000 mg/dL, or bilirubin of ≤50mg/dL. No hook effect was noted up to 500 pmol/L. PTH (1-84) did not cross-react in the assay. C-terminal PTHrP(107-139), and N-terminal PTHrP(1-36) had no significant cross-reactivity (≤1.1%). Mid-PTHrP(38-94) had 8.3% cross-reactivity. Comparison with an in-house PTHrP assay (n=267) showed an r2 of 0.96, and slope of 2.25 by Passing-Bablok regression fit. The 97.5% reference interval for PTHrP (n=114) was ≤0.7 pmol/L, however a higher concentration (≤4.2 pmol/L) was identified as a more specific clinical cut-off. A retrospective clinical validation study showed that using ≤4.2 pmol/L resulted in a 91% clinical sensitivity and a 98% clinical specificity. Conclusion: We have developed an analytically and clinically sensitive and specific PTHrP immunoassay. A cutoff of ≤4.2 pmol/L is clinically useful in the evaluation of patients suspected of hypercalcemia of malignancy.