What Is the Persistence to Methotrexate in Rheumatoid Arthritis, and Does Machine Learning Outperform Hypothesis‐Based Approaches to Its Prediction?
Open Access
- 4 June 2021
- journal article
- research article
- Published by Wiley in ACR Open Rheumatology
- Vol. 3 (7), 457-463
- https://doi.org/10.1002/acr2.11266
Abstract
Objective The objectives of this study were to assess the 1-year persistence to methotrexate (MTX) initiated as the first ever conventional synthetic disease-modifying antirheumatic drug in new-onset rheumatoid arthritis (RA) and to investigate the marginal gains and robustness of the results by increasing the number and nature of covariates and by using data-driven, instead of hypothesis-based, methods to predict this persistence. Methods Through the Swedish Rheumatology Quality Register, linked to other data sources, we identified a cohort of 5475 patients with new-onset RA in 2006-2016 who were starting MTX monotherapy as their first disease-modifying antirheumatic drug. Data on phenotype at diagnosis and demographics were combined with increasingly detailed data on medical disease history and medication use in four increasingly complex data sets (48-4162 covariates). We performed manual model building using logistic regression. We also performed five different machine learning (ML) methods and combined the ML results into an ensemble model. We calculated the area under the receiver operating characteristic curve (AUROC) and made calibration plots. We trained on 90% of the data, and tested the models on a holdout data set. Results Of the 5475 patients, 3834 (70%) remained on MTX monotherapy 1 year after treatment start. Clinical RA disease activity and baseline characteristics were most strongly associated with the outcome. The best manual model had an AUROC of 0.66 (95% confidence interval [CI] 0.60-0.71). For the ML methods, Lasso regression performed best (AUROC = 0.67; 95% CI 0.62-0.71). Conclusion Approximately two thirds of patients with early RA who start MTX remain on this therapy 1 year later. Predicting this persistence remains a challenge, whether using hypothesis-based or ML models, and may yet require additional types of data.Funding Information
- VINNOVA
This publication has 18 references indexed in Scilit:
- Genetic and epigenetic predictors of responsiveness to treatment in RANature Reviews Rheumatology, 2014
- Old drugs, old problems: where do we stand in prediction of rheumatoid arthritis responsiveness to methotrexate and other synthetic DMARDs?BMC Medicine, 2013
- Reduction of long‐term disability in inflammatory polyarthritis by early and persistent suppression of joint inflammation: Results from the Norfolk Arthritis RegisterArthritis Care & Research, 2011
- Predictors of response to methotrexate in early DMARD naïve rheumatoid arthritis: results from the initial open-label phase of the SWEFOT trialAnnals Of The Rheumatic Diseases, 2010
- Early treatment with, and time receiving, first disease-modifying antirheumatic drug predicts long-term function in patients with inflammatory polyarthritisAnnals Of The Rheumatic Diseases, 2009
- Can clinical factors at presentation be used to predict outcome of treatment with methotrexate in patients with early inflammatory polyarthritis?Annals Of The Rheumatic Diseases, 2008
- GLUMIP2.0:SAS/IMLSoftware for Planning Internal PilotsJournal of Statistical Software, 2008
- Building Predictive Models inRUsing thecaretPackageJournal of Statistical Software, 2008
- A clinical pharmacogenetic model to predict the efficacy of methotrexate monotherapy in recent‐onset rheumatoid arthritisArthritis & Rheumatism, 2007