Maxime Verhoeven

61 Validation of a prediction model for insufficient response to MTX INTRODUCTION Methotrexate (MTX) is the first-line therapy in rheumatoid arthritis (RA). 1 Although efficacious in a large proportion of patients, MTX is poorly effective in approximately 30% of early RA patients. 2,3 Patients on MTX who do not show improvement at 3 months (insufficient responders) or do not reach the treatment target of low disease activity/ remission at 6 months (non-responders) are switched to biologic disease modifying anti-rheumatic drug (bDMARD) therapies or novel targeted synthetic DMARD (tsDMARD) therapies, including e.g., Janus kinase (JAK) inhibitors, 1,4,5 with or without concomitant MTX treatment. To ensure that only patients unresponsive to MTX receive early (additional) treatment with b/tsDMARDs and those responsive to MTX are spared costly biologics or synthetic drugs, we and others have constructed models to predict MTX (non)-response. 6–9 Our prognostic multivariable prediction model for the prediction of insufficient response, defined as: disease activity score assessing 28 joints (DAS28; DAS28>3.2) at 3 months of MTX therapy, was constructed in the treatment in the Rotterdam Early Arthritis Cohort (tREACH) and included clinical predictors (DAS28 and Health Assessment Questionnaire (HAQ)), life style predictors (smoking and BMI) and laboratory parameters involved in MTX metabolism (erythrocyte folate and single nucleotide polymorphisms: SNPs). 9 This model classified 80% of patients correctly (area under the curve (AUC) of the receiver operating characteristic (ROC): 0.80 (95%CI: 0.73 – 0.86)) and was externally validated in the MTX-Rotterdam cohort showing a similar prognostic performance (AUC 0.80 (95%CI: 0.69 – 0.91)) even though BMI and smoking predictors were absent from this validation cohort. 9 The aim of the current study was to validate the complete prediction model, including BMI and smoking status predictors, in an external early RA cohort (U-Act- Early) from a different geographic region and to enhance the model’s applicability in clinical practice. 10 METHODS The methodology of this study followed transparent reporting of a multivariable prediction model for individual prognosis or diagnosis (TRIPOD) guidelines. 11 Patients The external validation cohort consisted of 91 patients from the U-Act-Early cohort, a multicenter, double blind, placebo-controlled strategy trial, registered at ClinicalTrials. gov (number: NCT01034137). 10 DMARD- and glucocorticoid (GC)-naïve early RA patients were eligible for inclusion once classified as RA patients according to the 1987 America 4