Advanced machine learning for predicting individual risk of flares in rheumatoid arthritis patients tapering biologic drugs.


Journal

Arthritis research & therapy
ISSN: 1478-6362
Titre abrégé: Arthritis Res Ther
Pays: England
ID NLM: 101154438

Informations de publication

Date de publication:
27 02 2021
Historique:
received: 13 04 2020
accepted: 10 02 2021
entrez: 28 2 2021
pubmed: 1 3 2021
medline: 22 6 2021
Statut: epublish

Résumé

Biological disease-modifying anti-rheumatic drugs (bDMARDs) can be tapered in some rheumatoid arthritis (RA) patients in sustained remission. The purpose of this study was to assess the feasibility of building a model to estimate the individual flare probability in RA patients tapering bDMARDs using machine learning methods. Longitudinal clinical data of RA patients on bDMARDs from a randomized controlled trial of treatment withdrawal (RETRO) were used to build a predictive model to estimate the probability of a flare. Four basic machine learning models were trained, and their predictions were additionally combined to train an ensemble learning method, a stacking meta-classifier model to predict the individual flare probability within 14 weeks after each visit. Prediction performance was estimated using nested cross-validation as the area under the receiver operating curve (AUROC). Predictor importance was estimated using the permutation importance approach. Data of 135 visits from 41 patients were included. A model selection approach based on nested cross-validation was implemented to find the most suitable modeling formalism for the flare prediction task as well as the optimal model hyper-parameters. Moreover, an approach based on stacking different classifiers was successfully applied to create a powerful and flexible prediction model with the final measured AUROC of 0.81 (95%CI 0.73-0.89). The percent dose change of bDMARDs, clinical disease activity (DAS-28 ESR), disease duration, and inflammatory markers were the most important predictors of a flare. Machine learning methods were deemed feasible to predict flares after tapering bDMARDs in RA patients in sustained remission.

Sections du résumé

BACKGROUND
Biological disease-modifying anti-rheumatic drugs (bDMARDs) can be tapered in some rheumatoid arthritis (RA) patients in sustained remission. The purpose of this study was to assess the feasibility of building a model to estimate the individual flare probability in RA patients tapering bDMARDs using machine learning methods.
METHODS
Longitudinal clinical data of RA patients on bDMARDs from a randomized controlled trial of treatment withdrawal (RETRO) were used to build a predictive model to estimate the probability of a flare. Four basic machine learning models were trained, and their predictions were additionally combined to train an ensemble learning method, a stacking meta-classifier model to predict the individual flare probability within 14 weeks after each visit. Prediction performance was estimated using nested cross-validation as the area under the receiver operating curve (AUROC). Predictor importance was estimated using the permutation importance approach.
RESULTS
Data of 135 visits from 41 patients were included. A model selection approach based on nested cross-validation was implemented to find the most suitable modeling formalism for the flare prediction task as well as the optimal model hyper-parameters. Moreover, an approach based on stacking different classifiers was successfully applied to create a powerful and flexible prediction model with the final measured AUROC of 0.81 (95%CI 0.73-0.89). The percent dose change of bDMARDs, clinical disease activity (DAS-28 ESR), disease duration, and inflammatory markers were the most important predictors of a flare.
CONCLUSION
Machine learning methods were deemed feasible to predict flares after tapering bDMARDs in RA patients in sustained remission.

Identifiants

pubmed: 33640008
doi: 10.1186/s13075-021-02439-5
pii: 10.1186/s13075-021-02439-5
pmc: PMC7913400
doi:

Substances chimiques

Antirheumatic Agents 0
Biological Products 0
Biomarkers 0

Types de publication

Journal Article Randomized Controlled Trial Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

67

Références

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Auteurs

Asmir Vodencarevic (A)

Digital Health, Siemens Healthcare GmbH, 91052, Erlangen, Germany.

Koray Tascilar (K)

Department of Internal Medicine 3 - Rheumatology and Immunology, Friedrich-Alexander University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen, 91054, Erlangen, Germany.
Deutsches Zentrum fuer Immuntherapie (DZI), 91054, Erlangen, Germany.

Fabian Hartmann (F)

Department of Internal Medicine 3 - Rheumatology and Immunology, Friedrich-Alexander University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen, 91054, Erlangen, Germany.
Deutsches Zentrum fuer Immuntherapie (DZI), 91054, Erlangen, Germany.

Michaela Reiser (M)

Department of Internal Medicine 3 - Rheumatology and Immunology, Friedrich-Alexander University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen, 91054, Erlangen, Germany.
Deutsches Zentrum fuer Immuntherapie (DZI), 91054, Erlangen, Germany.

Axel J Hueber (AJ)

Department of Internal Medicine 3 - Rheumatology and Immunology, Friedrich-Alexander University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen, 91054, Erlangen, Germany.
Deutsches Zentrum fuer Immuntherapie (DZI), 91054, Erlangen, Germany.
Section Rheumatology, Sozialstiftung Bamberg, 96049, Bamberg, Germany.

Judith Haschka (J)

Department of Internal Medicine 3 - Rheumatology and Immunology, Friedrich-Alexander University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen, 91054, Erlangen, Germany.
Deutsches Zentrum fuer Immuntherapie (DZI), 91054, Erlangen, Germany.
Vinforce Study Group, St. Vincent Hospital, Medical University of Vienna, 1090, Vienna, Austria.

Sara Bayat (S)

Department of Internal Medicine 3 - Rheumatology and Immunology, Friedrich-Alexander University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen, 91054, Erlangen, Germany.
Deutsches Zentrum fuer Immuntherapie (DZI), 91054, Erlangen, Germany.

Timo Meinderink (T)

Department of Internal Medicine 3 - Rheumatology and Immunology, Friedrich-Alexander University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen, 91054, Erlangen, Germany.
Deutsches Zentrum fuer Immuntherapie (DZI), 91054, Erlangen, Germany.

Johannes Knitza (J)

Department of Internal Medicine 3 - Rheumatology and Immunology, Friedrich-Alexander University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen, 91054, Erlangen, Germany.
Deutsches Zentrum fuer Immuntherapie (DZI), 91054, Erlangen, Germany.

Larissa Mendez (L)

Department of Internal Medicine 3 - Rheumatology and Immunology, Friedrich-Alexander University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen, 91054, Erlangen, Germany.
Deutsches Zentrum fuer Immuntherapie (DZI), 91054, Erlangen, Germany.

Melanie Hagen (M)

Department of Internal Medicine 3 - Rheumatology and Immunology, Friedrich-Alexander University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen, 91054, Erlangen, Germany.
Deutsches Zentrum fuer Immuntherapie (DZI), 91054, Erlangen, Germany.

Gerhard Krönke (G)

Department of Internal Medicine 3 - Rheumatology and Immunology, Friedrich-Alexander University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen, 91054, Erlangen, Germany.
Deutsches Zentrum fuer Immuntherapie (DZI), 91054, Erlangen, Germany.

Jürgen Rech (J)

Department of Internal Medicine 3 - Rheumatology and Immunology, Friedrich-Alexander University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen, 91054, Erlangen, Germany.
Deutsches Zentrum fuer Immuntherapie (DZI), 91054, Erlangen, Germany.

Bernhard Manger (B)

Department of Internal Medicine 3 - Rheumatology and Immunology, Friedrich-Alexander University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen, 91054, Erlangen, Germany.
Deutsches Zentrum fuer Immuntherapie (DZI), 91054, Erlangen, Germany.

Arnd Kleyer (A)

Department of Internal Medicine 3 - Rheumatology and Immunology, Friedrich-Alexander University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen, 91054, Erlangen, Germany.
Deutsches Zentrum fuer Immuntherapie (DZI), 91054, Erlangen, Germany.

Marcus Zimmermann-Rittereiser (M)

Digital Health, Siemens Healthcare GmbH, 91052, Erlangen, Germany.

Georg Schett (G)

Department of Internal Medicine 3 - Rheumatology and Immunology, Friedrich-Alexander University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen, 91054, Erlangen, Germany.
Deutsches Zentrum fuer Immuntherapie (DZI), 91054, Erlangen, Germany.

David Simon (D)

Department of Internal Medicine 3 - Rheumatology and Immunology, Friedrich-Alexander University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen, 91054, Erlangen, Germany. david.simon@uk-erlangen.de.
Deutsches Zentrum fuer Immuntherapie (DZI), 91054, Erlangen, Germany. david.simon@uk-erlangen.de.

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