Rudy Hidayat, Fara Fauzia, Suryo Anggoro Kusumo Wibowo, Anna Ariane, Radiyati Umi Partan, Putri Muthia, Ika Vemilia Warlisti, Bantar Suntoko, Mirza Zaka Pratama, Cesarius Singgih Wahono, Lita Diah Rahmawati, Pande Ketut Kurniari, Anggarda Kristianti Utomo, Najirman Najirman, Eka Kurniawan, Yulyani Werdiningsih, Faridin Pango, Mochammad Alfansyah Dhifanra, Jessica Audrey, Faisal Parlindungan
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 (p = 0.31). Decision curve analysis demonstrated that the scoring system provided a higher net benefit compared to default strategies across a threshold probability range of 35%–80%. 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. © The Author(s), 2026. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).
Rheumatology Division, Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia, Dr Cipto Mangunkusumo National Central General Hospital, Jakarta, 10430, Indonesia; Jakarta Rheumatic & Autoimmune Disease Study Group (Jak-RAIDS), Jakarta, Indonesia; Faculty of Medicine, Batam International University, Riau Islands, Indonesia; Rheumatology Division, Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia, Dr. Cipto Mangunkusumo National Central General Hospital, Jakarta, Indonesia; Rheumatology Division, Department of Internal Medicine, Faculty of Medicine, Universitas Sriwijaya, Mohammad Hoesin General Hospital, Palembang, Indonesia; Rheumatology Division, Department of Internal Medicine, Faculty of Medicine, Universitas Diponegoro, Dr Kariadi General Hospital, Semarang, Indonesia; Rheumatology Division, Department of Internal Medicine, Faculty of Medicine, Universitas Brawijaya, Saiful Anwar General Hospital, Malang, Indonesia; Rheumatology Division, Department of Internal Medicine, Faculty of Medicine, Universitas Airlangga, Dr Soetomo General Hospital, Surabaya, Indonesia; Rheumatology Division, Department of Internal Medicine, Faculty of Medicine, Universitas Udayana, Ngoerah General Hospital, Bali, Denpasar, Indonesia; Rheumatology Division Department of Internal Medicine, Faculty of Medicine, Universitas Lambung Mangkurat, Ulin General Hospital, Banjarmasin, Indonesia; Rheumatology Division, Department of Internal Medicine, Faculty of Medicine, Universitas Andalas, Dr M Djamil General Hospital, Padang, Indonesia; Rheumatology Division, Department of Internal Medicine, Faculty of Medicine, Universitas Sebelas Maret, Dr Moewardi General Hospital, Surakarta, Indonesia; Rheumatology Division, Department of Internal Medicine, Faculty of Medicine, Universitas Hasanuddin, Dr Wahidin Sudirohusodo General Hospital, Makassar, Indonesia; Rheumatology Division, Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia, Dr Cipto Mangunkusumo National Central General Hospital, Jakarta, Indonesia; Medical Staff Group of Internal Medicine, Universitas Indonesia Hospital, Depok, Indonesia
