Interpretable machine learning models for predicting short-term prognosis in AChR-Ab+ generalized myasthenia gravis using clinical features and systemic inflammation index.

Abstract

Myasthenia Gravis (MG) is an autoimmune disease that causes muscle weakness in 80% of patients, most of whom test positive for anti-acetylcholine receptor (AChR) antibodies (AChR-Abs). Predicting and improving treatment outcomes are necessary due to varying responses, ranging from complete relief to minimal improvement. Our study aims to develop and validate an interpretable machine learning (ML) model that integrates systemic inflammation indices with traditional clinical indicators. The goal is to predict the short-term prognosis (after 6 months of treatment) of AChR-Ab+ generalized myasthenia gravis (GMG) patients to guide personalized treatment strategies. We performed a retrospective analysis on 202 AChR-Ab+ GMG patients, dividing them into training and external validation cohorts. The primary outcome of this study was the Myasthenia Gravis Foundation of America (MGFA) post-intervention status assessed after 6 months of treatment initiation. Prognoses were classified as "unchanged or worse" for a poor outcome and "improved or better" for a good outcome. Accordingly, patients were categorized into "good outcome" or "poor outcome" groups. In the training cohort, we developed and internally validated various ML models using systemic inflammation indices, clinical indicators, or a combination of both. We then carried out external validation with the designated cohort. Additionally, we assessed the feature importance of our most effective model using the Shapley Additive Explanations (SHAP) method. In our study of 202 patients, 28.7% (58 individuals) experienced poor outcomes after 6 months of standard therapy. We identified 11 significant predictors, encompassing both systemic inflammation indexes and clinical metrics. The extreme gradient boosting (XGBoost) model demonstrated the best performance, achieving an area under the receiver operating characteristic (ROC) curve (AUC) of 0.944. This was higher than that achieved by logistic regression (Logit) (AUC: 0.882), random forest (RF) (AUC: 0.917), support vector machines (SVM) (AUC: 0.872). Further refinement through SHAP analysis highlighted five critical determinants-two clinical indicators and three inflammation indexes-as crucial for assessing short-term prognosis in AChR-Ab+ GMG patients. Our analysis confirms that the XGBoost model, integrating clinical indicators with systemic inflammation indexes, effectively predicts short-term prognosis in AChR-Ab+ GMG patients. This approach enhances clinical decision-making and improves patient outcomes.