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Development and validation of a prognostic multivariable model to predict insufficient clinical response to methotrexate in rheumatoid arthritis
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Development and validation of a prognostic multivariable model to predict insufficient clinical response to methotrexate in rheumatoid arthritis
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Development and validation of a prognostic multivariable model to predict insufficient clinical response to methotrexate in rheumatoid arthritis
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Journal Article
Development and validation of a prognostic multivariable model to predict insufficient clinical response to methotrexate in rheumatoid arthritis
2018
Overview
The objective was to predict insufficient response to 3 months methotrexate (MTX) in DMARD naïve rheumatoid arthritis patients.
A Multivariable logistic regression model of rheumatoid arthritis patients starting MTX was developed in a derivation cohort with 285 patients starting MTX in a clinical multicentre, stratified single-blinded trial, performed in seven secondary care clinics and a tertiary care clinic. The model was validated in a validation cohort with 102 patients starting MTX at a tertiary care clinic. Outcome was insufficient response (disease activity score (DAS)28 >3.2) after 3 months of MTX treatment. Clinical characteristics, lifestyle variables, genetic and metabolic biomarkers were determined at baseline in both cohorts. These variables were dichotomized and used to construct a multivariable prediction model with backward logistic regression analysis.
The prediction model for insufficient response in the derivation cohort, included: DAS28>5.1, Health Assessment Questionnaire>0.6, current smoking, BMI>25 kg/m2, ABCB1 rs1045642 genotype, ABCC3 rs4793665 genotype, and erythrocyte-folate<750 nmol/L. In the derivation cohort, AUC of ROC curve was 0.80 (95%CI: 0.73-0.86), and 0.80 (95%CI: 0.69-0.91) in the validation cohort. Betas of the prediction model were transformed into total risk score (range 0-8). At cutoff of ≥4, probability for insufficient response was 44%. Sensitivity was 71%, specificity 72%, with positive and negative predictive value of 72% and 71%.
A prognostics prediction model for insufficient response to MTX in 2 prospective RA cohorts by combining genetic, metabolic, clinical and lifestyle variables was developed and validated. This model satisfactorily identified RA patients with high risk of insufficient response to MTX.
Publisher
Public Library of Science,Public Library of Science (PLoS)
Subject
/ Analysis
/ Antirheumatic Agents - therapeutic use
/ Arthritis, Rheumatoid - drug therapy
/ Arthritis, Rheumatoid - pathology
/ ATP Binding Cassette Transporter, Subfamily B - genetics
/ Blood
/ Female
/ Humans
/ Male
/ Medicine and Health Sciences
/ Methotrexate - therapeutic use
/ Multidrug Resistance-Associated Proteins - genetics
/ Patients
/ Polymorphism, Single Nucleotide
/ Research and Analysis Methods
/ Smoking
