ArticleTherapeutic advances in musculoskeletal disease2026
Development and validation of a clinical scoring system for the prediction of methotrexate treatment response in rheumatoid arthritis patients: a multicenter real-world study.
Article in Therapeutic advances in musculoskeletal disease, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Methotrexate (MTX) remains the anchor drug in rheumatoid arthritis (RA) management. However, treatment response varies widely. Objectives: This study aimed to develop and validate a simple scoring model for predicting MTX monotherapy treatment success at 6 months. Methods: We conducted a multicenter, retrospective cohort study of newly diagnosed, disease-modifying antirheumatic drug-naïve RA patients treated with MTX monotherapy. Treatment success was defined as achieving remission or low disease activity at 6 months based on Disease Activity Score-28 with erythrocyte sedimentation rate (DAS28-ESR). Multivariable logistic regression was used to identify baseline predictors and construct a scoring model. Internal validation was performed using stratified 10-fold cross-validation and bootstrap resampling, while external validation was conducted in an independent cohort from three hospitals. Model performance was evaluated by discrimination and calibration. Results: The development cohort included 840 patients. Four independent predictors of MTX success were identified: age >60 years, normal ESR, lower baseline disease activity (DAS28-ESR ⩽5.1), and lower glucocorticoid dose. The model demonstrated an area under the ROC curve (AUC) of 0.66. Internal validation yielded a mean AUC of 0.65, with a calibration intercept of -0.001 and slope of 0.943. Bootstrap analysis showed minimal optimism (0.003). External validation in 265 patients showed moderate discrimination (AUC 0.63; 95% confidence interval 0.56-0.70) with acceptable calibration (intercept 0.16; slope 0.890) and a stable Brier score of 0.23. No significant difference in AUC was observed between cohorts ( Conclusion: The MTX response scoring system demonstrated stable performance and may serve as an adjunctive tool to aid in early risk stratification for MTX treatment success, particularly in resource-limited settings.
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