TY - JOUR
T1 - Prediction of Methotrexate Intolerance in Juvenile Idiopathic Arthritis
T2 - a prospective, observational cohort study
AU - van Dijkhuizen, Evert Hendrik Pieter
AU - Bulatovic, Maja
AU - Pluijm, Saskia M. F.
AU - de Rotte, Maurits C. F. J.
AU - Vastert, SJ
AU - Kamphuis, Sylvia
AU - de Jonge, Robert
AU - Wulffraat, NM
PY - 2015/2/18
Y1 - 2015/2/18
N2 - Background: Methotrexate (MTX) is an effective and safe drug in the treatment of juvenile idiopathic arthritis (JIA). Despite its safety, MTX-related gastrointestinal adverse effects before and after MTX administration, termed MTX intolerance, occur frequently, leading to non-compliance and potentially premature MTX termination. The aim of this study was to construct a risk model to predict MTX intolerance.Methods: In a prospective JIA cohort, clinical variables and single nucleotide polymorphisms were determined at MTX start. The Methotrexate Intolerance Severity Score was employed to measure MTX intolerance in the first year of treatment. MTX intolerance was most prevalent at 6 or 12 months after MTX start, which was defined as the outcome for the prediction model. The model was developed in 152 patients using multivariable logistic regression analysis and subsequently internally validated using bootstrapping.Results: The prediction model included the following predictors: JIA category, antinuclear antibody, parent/patient assessment of pain, Juvenile Arthritis Disease Activity Score-27, thrombocytes, alanine aminotransferase and creatinine. The model classified 77.5% of patients correctly, and 66.7% of patients after internal validation by bootstrapping. The lowest predicted risk of MTX intolerance was 18.9% and the highest predicted risk was 85.9%. The prediction model was transformed into a risk score (range 0-17). At a cut-off of >= 6, sensitivity was 82.0%, specificity 56.1%, positive predictive value was 58.7% and negative predictive value 80.4%.Conclusions: This clinical prediction model showed moderate predictive power to detect MTX intolerance. To develop into a clinically usable tool, it should be validated in an independent cohort and updated with new predictors. Such an easy-to-use tool could then assist clinicians in identifying patients at risk to develop MTX intolerance, and in turn to monitor them closely and intervene timely in order to prevent the development of MTX intolerance.
AB - Background: Methotrexate (MTX) is an effective and safe drug in the treatment of juvenile idiopathic arthritis (JIA). Despite its safety, MTX-related gastrointestinal adverse effects before and after MTX administration, termed MTX intolerance, occur frequently, leading to non-compliance and potentially premature MTX termination. The aim of this study was to construct a risk model to predict MTX intolerance.Methods: In a prospective JIA cohort, clinical variables and single nucleotide polymorphisms were determined at MTX start. The Methotrexate Intolerance Severity Score was employed to measure MTX intolerance in the first year of treatment. MTX intolerance was most prevalent at 6 or 12 months after MTX start, which was defined as the outcome for the prediction model. The model was developed in 152 patients using multivariable logistic regression analysis and subsequently internally validated using bootstrapping.Results: The prediction model included the following predictors: JIA category, antinuclear antibody, parent/patient assessment of pain, Juvenile Arthritis Disease Activity Score-27, thrombocytes, alanine aminotransferase and creatinine. The model classified 77.5% of patients correctly, and 66.7% of patients after internal validation by bootstrapping. The lowest predicted risk of MTX intolerance was 18.9% and the highest predicted risk was 85.9%. The prediction model was transformed into a risk score (range 0-17). At a cut-off of >= 6, sensitivity was 82.0%, specificity 56.1%, positive predictive value was 58.7% and negative predictive value 80.4%.Conclusions: This clinical prediction model showed moderate predictive power to detect MTX intolerance. To develop into a clinically usable tool, it should be validated in an independent cohort and updated with new predictors. Such an easy-to-use tool could then assist clinicians in identifying patients at risk to develop MTX intolerance, and in turn to monitor them closely and intervene timely in order to prevent the development of MTX intolerance.
KW - Juvenile idiopathic arthritis
KW - Methotrexate
KW - Adverse events
KW - Methotrexate intolerance
KW - Prediction model
KW - Predictor
KW - RHEUMATOID-ARTHRITIS
KW - MTHFR POLYMORPHISMS
KW - ADVERSE EVENTS
KW - FOLATE PATHWAY
KW - FOLINIC ACID
KW - MTX TOXICITY
KW - EFFICACY
KW - CHILDREN
KW - ASSOCIATION
KW - VALIDATION
U2 - 10.1186/s12969-015-0002-3
DO - 10.1186/s12969-015-0002-3
M3 - Article
C2 - 25745368
SN - 1546-0096
VL - 13
JO - Pediatric Rheumatology
JF - Pediatric Rheumatology
M1 - 5
ER -