CC BY 4.0Ihne-Schubert, Sandra M.Sandra M.Ihne-SchubertKircher, MalteMalteKircherWerner, Rudolf A.Rudolf A.WernerLapa, ConstantinConstantinLapaEinsele, HermannHermannEinseleGeier, AndreasAndreasGeierSchubert, TorbenTorbenSchubert2023-08-282024-06-032023-08-282023https://doi.org/10.24406/publica-1805https://publica.fraunhofer.de/handle/publica/448798https://doi.org/10.24406/publica-180510.1371/journal.pone.028992110.24406/publica-1805Background: Statistical analyses of clinical data are a cornerstone in understanding pathomechanisms of disorders. In rare disorders, cross-sectional datasets of sufficient size are usually not available. Taking AA amyloidosis as an example of a life-threatening rare disorder resulting from of uncontrolled chronic inflammation, we propose techniques from time series analysis to predict organ response to treatment. The advantage of time-series analysis is that it solely relies on temporal variation and therefore allows analyzing organ response to treatment even when the cross-sectional dimension is small. Methods: The joint temporal interdependence of inflammatory activity and organ response was modelled multivariately using vector autoregression (VAR) based on a unique 4.5 year spanning data set of routine laboratory, imaging data (e.g., 18F-Florbetaben-PET/CT) and functional investigations of a 68-year-old patient with multi-organ involvement of AA amyloidosis due to ongoing inflammatory activity of a malignant paraganglioma in stable disease for >20 years and excellent response to tocilizumab). Results: VAR analysis showed that alterations in inflammatory activity forecasted alkaline phosphatase (AP). AP levels, but not inflammatory activity at the previous measurement time point predicted proteinuria. Conclusion: We demonstrate the feasibility and value of time series analysis for obtaining clinically reliable information when the rarity of a disease prevents conventional prognostic modelling approaches. We illustrate the comparative utility of blood, functional and imaging markers to monitor the development and regression of AA amyloidosis.enjournal article