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Patient groups in Rheumatoid arthritis identified by deep learning respond differently to biologic or targeted synthetic DMARDs

Abstract:
Cycling of biologic or targeted synthetic disease modifying antirheumatic drugs (b/tsDMARDs) in rheumatoid arthritis (RA) patients due to non-response is a problem preventing and delaying disease control. We aimed to assess and validate treatment response of b/tsDMARDs among clusters of RA patients identified by deep learning. We clustered RA patients clusters at first-time b/tsDMARD (cohort entry) in the Swiss Clinical Quality Management in Rheumatic Diseases registry (SCQM) [1999-2018]. We performed comparative effectiveness analyses of b/tsDMARDs (ref. adalimumab) using Cox proportional hazard regression. Within 15 months, we assessed b/tsDMARD stop due to non-response, and separately a >= 20% reduction in DAS28-esr as a response proxy. We validated results through stratified analyses according to most distinctive patient characteristics of clusters. Clusters comprised between 362 and 1481 patients (3516 unique patients). Stratified (validation) analyses confirmed comparative effectiveness results among clusters: Patients with >= 2 conventional synthetic DMARDs and prednisone at b/tsDMARD initiation, male patients, as well as patients with a lower disease burden responded better to tocilizumab than to adalimumab (hazard ratio [HR] 5.46, 95% confidence interval [CI] [1.76-16.94], and HR 8.44 [3.43-20.74], and HR 3.64 [2.04-6.49], respectively). Furthermore, seronegative women without use of prednisone at b/tsDMARD initiation as well as seropositive women with a higher disease burden and longer disease duration had a higher risk of non-response with golimumab (HR 2.36 [1.03-5.40] and HR 5.27 [2.10-13.21], respectively) than with adalimumab. Our results suggest that RA patient clusters identified by deep learning may have different responses to first-line b/tsDMARD. Thus, it may suggest optimal first-line b/tsDMARD for certain RA patients, which is a step forward towards personalizing treatment. However, further research in other cohorts is needed to verify our results.ISSN:1553-734XISSN:1553-735
Publication status:
Published
Peer review status:
Peer reviewed

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10.1371/journal.pcbi.1011073

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Author
ORCID:
0000-0003-4581-8810
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Role:
Author
ORCID:
0000-0001-7082-8530
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Author
ORCID:
0000-0002-3486-7345
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Author
ORCID:
0000-0002-3276-9581
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Institution:
University of Oxford
Role:
Author
ORCID:
0000-0003-1313-4473


Publisher:
Public Library of Science
Journal:
PLoS Computational Biology More from this journal
Volume:
19
Issue:
6
Pages:
e1011073-e1011073
Publication date:
2023-06-02
DOI:
EISSN:
1553-7358
ISSN:
1553-734X


Language:
English
Keywords:
Pubs id:
2371157
Local pid:
pubs:2371157
Source identifiers:
W4379114171
Deposit date:
2026-02-13
ARK identifier:
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