Vector autoregression: Useful in rare diseases?-Predicting organ response patterns in a rare case of secondary AA amyloidosis.

BACKGROUND

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.

Informations de copyright

Copyright: © 2023 Ihne-Schubert et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Déclaration de conflit d'intérêts

Sandra Ihne-Schubert S. Ihne-Schubert received financial reimbursement for consulting, advisory board activities, speaker honoraries and/or travel support to attend scientific meetings by Akcea Therapeutics, Alnylam, Pfizer, Janssen-Cilag, and Takeda, and further research funding from Pfizer and Akcea Therapeutics. An internship was supported by ONLUS. She was fellow of the local Clinician Scientist program of the IZKF Würzburg. Malte Kircher no conflicts of interest no conflicts of interest Rudolf A. Werner no conflicts of interest Constantin Lapa no conflicts of interest Hermann Einsele no conflicts of interest Andreas Geier A. Geier is Steering Committee member or advisor for AbbVie, Alexion, Bayer, BMS, Eisai, Falk, Gilead, Heel, Intercept, Ipsen, Merz, MSD, Novartis, Pfizer, Roche, Sanofi-Aventis, Sequana. He reports lecture fees from AbbVie, Advanz, Alexion, BMS, Burgerstein, CSL Behring, Falk, Gilead, Intercept, Merz, MSD, Novartis, Roche, Sequana and research grants from Intercept, Falk (both NAFLD CSG) and Novartis. Torben Schubert no conflicts of interest This does not alter our adherence to PLOS ONE policies on sharing data and materials.