Mortality Risk Prediction in Patients With Antimelanoma Differentiation-Associated, Gene 5 Antibody-Positive, Dermatomyositis-Associated Interstitial Lung Disease: Algorithm Development and Validation.

Abstract

Background: Patients with antimelanoma differentiation-associated gene 5 antibody-positive dermatomyositis-associated interstitial lung disease (anti-MDA5+DM-ILD) are susceptible to rapidly progressive interstitial lung disease (RP-ILD) and have a high risk of mortality. There is an urgent need for a reliable prediction model, accessible via an easy-to-use web-based tool, to evaluate the risk of death.

Objective: This study aimed to develop and validate a risk prediction model of 3-month mortality using machine learning (ML) in a large multicenter cohort of patients with anti-MDA5+DM-ILD in China.

Methods: In total, 609 consecutive patients with anti-MDA5+DM-ILD were retrospectively enrolled from 6 hospitals across China. Patient demographics and laboratory and clinical parameters were collected on admission. The primary endpoint was 3-month mortality due to all causes. Six ML algorithms (Extreme Gradient Boosting [XGBoost], logistic regression (LR), Light Gradient Boosting Machine [LightGBM], random forest [RF], support vector machine [SVM], and k-nearest neighbor [KNN]) were applied to construct and evaluate the model.

Results: After applying inclusion and exclusion criteria, 509 (83.6%) of the 609 patients were included in our study, divided into a training cohort (n=203, 39.9%), an internal validation cohort (n=51, 10%), and 2 external validation cohorts (n=92, 18.1%, and n=163, 32%). ML identified 8 important variables as critical for model construction: RP-ILD, erythrocyte sedimentation rate (ESR), serum albumin (ALB) level, age, C-reactive protein (CRP) level, aspartate aminotransferase (AST) level, lactate dehydrogenase (LDH) level, and the neutrophil-to-lymphocyte ratio (NLR). LR was chosen as the best algorithm for model construction, and the model demonstrated excellent performance, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.866, a sensitivity of 84.8%, and a specificity of 84.4% on the validation data set and an AUC of 0.90, a sensitivity of 85.0%, and a specificity of 83.9% on the training data set. Calibration curves and decision curve analysis (DCA) confirmed the model's accuracy and clinical applicability. Moreover, the model showed strong predictive performance in the external validation cohorts (cohort 1: AUC=0.836, 95% CI 0.754-0.916; cohort 2: AUC=0.915, 95% CI 0.871-0.959), indicating good generalizability. This model was integrated into a web-based tool to predict the 3-month mortality for patients with anti-MDA5+DM-ILD.

Conclusions: We successfully developed a robust clinical prediction model and an accompanying web tool to estimate the 3-month mortality risk for patients with anti-MDA5+DM-ILD.