Research Article: Prediction of chronic damage in systemic lupus erythematosus by using machine-learning models

Date Published: March 22, 2017

Publisher: Public Library of Science

Author(s): Fulvia Ceccarelli, Marco Sciandrone, Carlo Perricone, Giulio Galvan, Francesco Morelli, Luis Nunes Vicente, Ilaria Leccese, Laura Massaro, Enrica Cipriano, Francesca Romana Spinelli, Cristiano Alessandri, Guido Valesini, Fabrizio Conti, Masataka Kuwana.

http://doi.org/10.1371/journal.pone.0174200

Abstract

The increased survival in Systemic Lupus Erythematosus (SLE) patients implies the development of chronic damage, occurring in up to 50% of cases. Its prevention is a major goal in the SLE management. We aimed at predicting chronic damage in a large monocentric SLE cohort by using neural networks.

We enrolled 413 SLE patients (M/F 30/383; mean age ± SD 46.3±11.9 years; mean disease duration ± SD 174.6 ± 112.1 months). Chronic damage was assessed by the SLICC/ACR Damage Index (SDI). We applied Recurrent Neural Networks (RNNs) as a machine-learning model to predict the risk of chronic damage. The clinical data sequences registered for each patient during the follow-up were used for building and testing the RNNs.

At the first visit in the Lupus Clinic, 35.8% of patients had an SDI≥1. For the RNN model, two groups of patients were analyzed: patients with SDI = 0 at the baseline, developing damage during the follow-up (N = 38), and patients without damage (SDI = 0). We created a mathematical model with an AUC value of 0.77, able to predict damage development. A threshold value of 0.35 (sensitivity 0.74, specificity 0.76) seemed able to identify patients at risk to develop damage.

We applied RNNs to identify a prediction model for SLE chronic damage. The use of the longitudinal data from the Sapienza Lupus Cohort, including laboratory and clinical items, resulted able to construct a mathematical model, potentially identifying patients at risk to develop damage.

Partial Text

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by a multifactorial pathogenesis in which genetic and environmental factors interplay, determining disease development [1]. The production of a wide range of autoantibodies is a disease hallmark, leading to different clinical phenotypes [2]. The survival of SLE patients dramatically changed in the last 60 years, moving from the 50%, described in the 1950s, to the current over 90% [3]. The increased survival determined the possible accrual of chronic damage, related to adverse events of treatment, disease activity and comorbidities [4–6]. In order to quantify the damage in SLE patients and to measure over time modifications, the Systemic Lupus Collaborating Clinics (SLICC) and the American College of Rheumatology (ACR) proposed and validated a specific index, the SLICC/ACR Damage Index (SDI) [7]. Studies using such index in SLE cohorts demonstrated that damage accrual is associated with several demographic and clinical features including age and disease duration. Moreover, the presence of specific lupus-associated autoantibodies, such as anti-phospholipid antibodies (aPL), seems to be associated with damage development as well as disease activity, in particular, the occurrence of flares [8]. Nonetheless, some treatments such as glucocorticoids and immunosuppressive agents, despite their role in disease management, could intervene in determining chronic damage [4, 9].

We conducted a longitudinal study on adult SLE patients attending at the Sapienza Lupus Cohort. All patients satisfied the revised 1997 ACR criteria for SLE classification [19]. The local ethical committee of “Policlinico Umberto I/Sapienza Università di Roma” approved the study. Patients provided written informed consent at the time of the first visit at the Sapienza Lupus Clinic.

Four hundred and thirteen patients were enrolled consecutively in the present study (M/F 30/383; mean age ±SD 46.3±11.9 years; mean disease duration ±SD 174.6±112.1 months; Ethnicity: Caucasian 97.3%, Asian 1.7%, Latino-American 1.0%). Referring to the disease history, joint and skin involvement and hematological manifestations were the most frequent, occurring in 67.1%, 66.3% and 63.9% respectively. Patients were followed in the present outpatient clinic for a mean period ±SD of 63.9±30.7 months.

To the best of our knowledge, this is the first study aimed at developing an RNN model to predict chronic damage in a large SLE population-based data.

 

Source:

http://doi.org/10.1371/journal.pone.0174200

 

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