New insights from the application of the FAbry STabilization indEX in a large population of Fabry cases

摘要

Background The FAbry STabilization indEX (FASTEX) is an innovative index allowing the assessment of clinical stability over time in Fabry disease patients. This index was developed in a population of 28 male patients with the classical form of Fabry disease. Objectives The aim of the study was to test the accuracy of the FASTEX in evaluating Fabry disease stability in 132 male and female patients with classical and non-classical Fabry disease from nine Italian centres and it also aimed to define the sensitivity and specificity of this new tool. In particular, we aimed to investigate the correlation between the FASTEX and clinical judgement in a large-scale cohort of the study population. Methods Statistical methods applied to this investigation included the calculation of accuracy, specificity and sensitivity, receiver operating characteristic (ROC) curves and Cohen’s κ index related to the FASTEX and clinical judgement. Results The patient population included 58 males (43.9%). The mean age of the overall population was 46.3 ± 15. 1?years (range 31.2–61.4). The median interval between the two multidisciplinary evaluations used for FASTEX calculation was 398?days. Since no gold standard method is available to define the overall clinical condition of Fabry patients over time, the results of the FASTEX were compared with clinical judgements given by the physicians involved in this study. In this way, the FASTEX classified 121 of 132 (92%) patients correctly. In particular, the FASTEX correctly identified 93% (41/44) of clinically ‘unstable’ and 91% (80/88) of clinically ‘stable’ patients. The area under the curve of the ROC related to the FASTEX index cut-off (20) was equal to 0.967, very close to its theoretical maximum (1), which means that it is an excellent test for classifying patients as ‘stable’ or ‘unstable’ compared with clinical judgement. In addition, the FASTEX cut-off 20 provides the most acceptable balance between sensitivity and specificity. The Cohen’s κ index value obtained in our study was 0.82, showing a highly statistically significant P-value??0.01 related to the agreement between the FASTEX and clinical judgement. Conclusions The FASTEX is demonstrated here to be a specific and sensitive tool. When applied to a large cohort of Fabry patients, it was shown to be a valid instrument in helping physicians to discriminate objectively the clinical stability of individual Fabry patients.