ArticleRheumatology and therapy2020
Validation of a Prognostic Multivariable Prediction Model for Insufficient Clinical Response to Methotrexate in Early Rheumatoid Arthritis and Its Clinical Application in Evidencio.
Article in Rheumatology and therapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01034137 (U-ACT-EARLY), which is not on this map. Cited by 5 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
U-ACT-EARLY: A Multi-center, Randomized, Double Blind, Placebo Controlled Study to Evaluate Remission in DMARD and Biological naïve Early Rheumatoid Arthritis (RA) Subjects Treated With Tocilizumab (TCZ) Plus Tight Control Methotrexate (MTX) , TCZ Monotherapy or Tight Control MTX Monotherapy
Who cites it
5 citing papers in PubMed, 13 citations in OpenAlex.
- Development of machine learning models for predicting non-remission in early RA highlights the robust predictive importance of the RAID score-evidence from the ARCTIC study.Frontiers in medicine · 2025Article
- Pre-defined gene co-expression modules in rheumatoid arthritis transition towards molecular health following anti-TNF therapy.Rheumatology (Oxford, England) · 2022Article
- Early prediction of treatment response in rheumatoid arthritis by quantitative macrophage PET.RMD open · 2022Article
- Complex Machine-Learning Algorithms and Multivariable Logistic Regression on Par in the Prediction of Insufficient Clinical Response to Methotrexate in Rheumatoid Arthritis.Journal of personalized medicine · 2021Article
- Identification of Metabolic Biomarkers in Relation to Methotrexate Response in Early Rheumatoid Arthritis.Journal of personalized medicine · 2020Article
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Authors and funding
12 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionMethotrexate (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 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.
methodsErythrocyte folate and SNPs were assessed in 91 early disease-modifying antirheumatic drug (DMARD)-naïve RA patients starting MTX in the external validation cohort (U-Act-Early). Insufficient response (DAS28 > 3.2) was determined after 3 months and non-response after 6 months of therapy. The previously developed prediction model was considered successfully validated in the U-Act-Early (validation cohort) if the area under the curve (AUC) of the receiver operating characteristic (ROC) was not significantly lower than in the tREACH (derivation cohort).
resultsThe AUCs in U-Act-Early at three and 6 months were 0.75 (95% CI 0.64-0.85) and 0.71 (95% CI 0.60-0.82) respectively, similar to the tREACH. Baseline DAS28 > 5.1 and HAQ > 0.6 were the strongest predictors. The model was simplified by excluding the SNPs, while still classifying 73% correctly. Furthermore, interaction terms between BMI and HAQ and BMI and erythrocyte folate significantly improved the model increasing correct classification to 75%. Results were successfully implemented in Evidencio online platform assisting clinicians in shared decision-making to intensify treatment when appropriate.
conclusionsWe successfully externally validated our recently reported prediction model for MTX non-response and enhanced its clinical application thus enabling its evaluation in a clinical trial.
trial registrationThe U-Act-Early is registered at ClinicalTrials.gov. number: NCT01034137. tREACH is registered retrospectively at ISRCTN registry, number: ISRCTN26791028 at 23 August 2007.
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