Validation of a Prognostic Multivariable Prediction Model for Insufficient Clinical Response to Methotrexate in Early Rh
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ORIGINAL RESEARCH
Validation of a Prognostic Multivariable Prediction Model for Insufficient Clinical Response to Methotrexate in Early Rheumatoid Arthritis and Its Clinical Application in Evidencio Helen R. Gosselt
. Maxime M. A. Verhoeven . Maurits C. F. J. de Rotte . Saskia M. F. Pluijm .
´ alasan . Sandra G. Heil . Ittai B. Muller . Gerrit Jansen . Janneke Tekstra . Maja Bulatovic´-C Floris P. J. G. Lafeber . Johanna M. W. Hazes . Robert de Jonge Received: July 14, 2020 Ó The Author(s) 2020
ABSTRACT Introduction: Methotrexate (MTX) constitutes the first-line therapy in rheumatoid arthritis (RA), yet approximately 30% of the patients do not benefit from MTX. Recently, we reported a prognostic multivariable prediction model for insufficient clinical response to MTX at 3 Johanna M. W. Hazes and Robert de Jonge contributed equally to this manuscript as senior authors.
Digital Features To view digital features for this article go to: https://doi.org/10.6084/m9.figshare.12800714. Electronic Supplementary Material The online version of this article (https://doi.org/10.1007/s40744020-00230-7) contains supplementary material, which is available to authorized users. H. R. Gosselt (&) M. C. F. J. de Rotte I. B. Muller R. de Jonge Amsterdam Gastroenterology and Metabolism, Department of Clinical Chemistry, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands e-mail: [email protected] H. R. Gosselt S. G. Heil Department of Clinical Chemistry, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands M. M. A. Verhoeven J. Tekstra F. P. J. G. Lafeber Department of Rheumatology and Clinical Immunology, UMC Utrecht, Utrecht, The Netherlands
months of treatment in the treatment in the Rotterdam Early Arthritis Cohort (tREACH), including baseline predictors: Disease activity score 28 (DAS28), Health Assessment Questionnaire (HAQ), erythrocyte folate, single-nucleotide polymorphisms (SNPs; ABCB1, ABCC3), smoking, and BMI. The purpose of the current study was (1) to externally validate the model and (2) to enhance the model’s clinical applicability. Methods: Erythrocyte folate and SNPs were assessed in 91 early disease-modifying antirheumatic drug (DMARD)-naı¨ve RA patients starting MTX in the external validation cohort (U-Act-Early). Insufficient response (DAS28 [ 3.2) was determined after 3 months and nonresponse after 6 months of therapy. The previously developed prediction model was M. C. F. J. de Rotte Amsterdam Gastroenterology and Metabolism, Department of Clinical Chemistry, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands S. M. F. Pluijm Department of Paediatric Oncology, Prinses Ma´xima Centre for Paediatric Oncology, Utrecht, The Netherlands G. Jansen Amsterdam Rheumatology and Immunology Center, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
Rheumatol Ther
considered successfully validated in the U-ActEarly (validation cohort) if the area under the curve (AUC) of the receiver operating characteristic (ROC) was no
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