TY - JOUR
T1 - Development and validation of a prognostic multivariable model to predict insufficient clinical response to methotrexate in rheumatoid arthritis
AU - De Rotte, Maurits C.F.J.
AU - Pluijm, Saskia M.F.
AU - De Jong, Pascal H.P.
AU - Ćalasan, Maja Bulatović
AU - Wulffraat, Nico M.
AU - Weel, Angelique E.A.M.
AU - Lindemans, Jan
AU - Hazes, J. M.W.
AU - De Jonge, Robert
PY - 2018/12
Y1 - 2018/12
N2 - Objective The objective was to predict insufficient response to 3 months methotrexate (MTX) in DMARD naïve rheumatoid arthritis patients. Methods 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. Results The prediction model for insufficient response in the derivation cohort, included: DAS28>5.1, Health Assessment Questionnaire>0.6, current smoking, BMI>25 kg/m 2 , 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%. Conclusions 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.
AB - Objective The objective was to predict insufficient response to 3 months methotrexate (MTX) in DMARD naïve rheumatoid arthritis patients. Methods 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. Results The prediction model for insufficient response in the derivation cohort, included: DAS28>5.1, Health Assessment Questionnaire>0.6, current smoking, BMI>25 kg/m 2 , 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%. Conclusions 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.
UR - http://www.scopus.com/inward/record.url?scp=85058246041&partnerID=8YFLogxK
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85058246041&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/30532219
U2 - https://doi.org/10.1371/journal.pone.0208534
DO - https://doi.org/10.1371/journal.pone.0208534
M3 - Article
C2 - 30532219
SN - 1932-6203
VL - 13
JO - PLOS ONE
JF - PLOS ONE
IS - 12
M1 - e0208534
ER -