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- Santos-Valente, E, et al.
(författare)
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Biologicals in childhood severe asthma: the European PERMEABLE survey on the status quo
- 2021
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Ingår i: ERJ open research. - : European Respiratory Society (ERS). - 2312-0541. ; 7:3
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Tidskriftsartikel (refereegranskat)abstract
- Severe asthma is a rare disease in children, for which three biologicals, anti-immunoglobulin E, anti-interleukin-5 and anti-IL4RA antibodies, are available in European countries. While global guidelines exist on who should receive biologicals, knowledge is lacking on how those guidelines are implemented in real life and which unmet needs exist in the field. In this survey, we aimed to investigate the status quo and identify open questions in biological therapy of childhood asthma across Europe.MethodsStructured interviews regarding experience with biologicals, regulations on access to the different treatment options, drug selection, therapy success and discontinuation of therapy were performed. Content analysis was used to analyse data.ResultsWe interviewed 37 experts from 25 European countries and Turkey and found a considerable range in the number of children treated with biologicals per centre. All participating countries provide public access to at least one biological. Most countries allow different medical disciplines to prescribe biologicals to children with asthma, and only a few restrict therapy to specialised centres. We observed significant variation in the time point at which treatment success is assessed, in therapy duration and in the success rate of discontinuation. Most participating centres intend to apply a personalised medicine approach in the future to match patients a priori to available biologicals.ConclusionSubstantial differences exist in the management of childhood severe asthma across Europe, and the need for further studies on biomarkers supporting selection of biologicals, on criteria to assess therapy response and on how/when to end therapy in stable patients is evident.
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- De Meyer, Steffi, et al.
(författare)
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Plasma pTau181 and pTau217 predict asymptomatic amyloid accumulation equally well as amyloid PET
- 2024
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Ingår i: BRAIN COMMUNICATIONS. - 2632-1297. ; 6:4
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Tidskriftsartikel (refereegranskat)abstract
- The dynamic phase of preclinical Alzheimer's disease, as characterized by accumulating cortical amyloid-beta, is a window of opportunity for amyloid-beta-lowering therapies to have greater efficacy. Biomarkers that accurately predict amyloid-beta accumulation may be of critical importance for participant inclusion in secondary prevention trials and thus enhance development of early Alzheimer's disease therapies. We compared the abilities of baseline plasma pTau181, pTau217 and amyloid-beta PET load to predict future amyloid-beta accumulation in asymptomatic elderly. In this longitudinal cohort study, baseline plasma pTau181 and pTau217 were quantified using single molecule array assays in cognitively unimpaired elderly selected from the community-recruited F-PACK cohort based on the availability of baseline plasma samples and longitudinal amyloid-beta PET data (median time interval = 5 years, range 2-10 years). The predictive abilities of pTau181, pTau217 and PET-based amyloid-beta measures for PET-based amyloid-beta accumulation were investigated using receiver operating characteristic analyses, correlations and stepwise regression analyses. We included 75 F-PACK subjects (mean age = 70 years, 48% female), of which 16 were classified as amyloid-beta accumulators [median (interquartile range) Centiloid rate of change = 3.42 (1.60) Centiloids/year). Plasma pTau181 [area under the curve (95% confidence interval) = 0.72 (0.59-0.86)] distinguished amyloid-beta accumulators from non-accumulators with similar accuracy as pTau217 [area under the curve (95% confidence interval) = 0.75 (0.62-0.88) and amyloid-beta PET [area under the curve (95% confidence interval) = 0.72 (0.56-0.87)]. Plasma pTau181 and pTau217 strongly correlated with each other (r = 0.93, P-false discovery rate < 0.001) and, together with amyloid-beta PET, similarly correlated with amyloid-beta rate of change (r(pTau181) = 0.33, r(pTau217) = 0.36, r(amyloid-beta PET) = 0.35, all P-false discovery rate <= 0.01). Addition of plasma pTau181, plasma pTau217 or amyloid-beta PET to a linear demographic model including age, sex and APOE-epsilon 4 carriership similarly improved the prediction of amyloid-beta accumulation (Delta Akaike information criterion <= 4.1). In a multimodal biomarker model including all three biomarkers, each biomarker lost their individual predictive ability. These findings indicate that plasma pTau181, plasma pTau217 and amyloid-beta PET convey overlapping information and therefore predict the dynamic phase of asymptomatic amyloid-beta accumulation with comparable performances. In clinical trial recruitment, confirmatory PET scans following blood-based prescreening might thus not provide additional value for detecting participants in these early disease stages who are destined to accumulate cortical amyloid-beta. Given the moderate performances, future studies should investigate whether integrating plasma pTau species with other factors can improve performance and thus enhance clinical and research utility.
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