Predicting response to tocilizumab monotherapy in rheumatoid arthritis: A real-world data analysis using machine learning

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Predicting response to tocilizumab monotherapy in rheumatoid arthritis: A real-world data analysis using machine learning

Johansson, Fredrik, 1988 (author): Chalmers tekniska högskola,Chalmers University of Technology

Collins, Jamie (author): Brigham and Women's Hospital

Yau, Vincent (author): Genentech Inc.

Guan, Hongshu (author): Brigham and Women's Hospital

Kim, Seoyoung C. (author): Brigham and Women's Hospital

Losina, Elena (author): Brigham and Women's Hospital

Sontag, D. (author): Massachusetts Institute of Technology (MIT)

Stratton, Jacklyn (author): Brigham and Women's Hospital

Trinh, Huong (author): Genentech Inc.

Greenberg, Jeffrey (author): New York University

Solomon, Daniel H. (author): Brigham and Women's Hospital

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(creator_code:org_t)

2021-05-01
2021
English.
In: Journal of Rheumatology. - : The Journal of Rheumatology. - 1499-2752 .- 0315-162X. ; 48:9, s. 1364-1370

Related links:: https://www.research...; show more...; https://research.cha...; https://doi.org/10.3...; show less...

Journal article (peer-reviewed)

Abstract Subject headings

Objective. Tocilizumab (TCZ) has shown similar efficacy when used as monotherapy as in combination with other treatments for rheumatoid arthritis (RA) in randomized controlled trials (RCTs). We derived a remission prediction score for TCZ monotherapy (TCZm) using RCT data and performed an external validation of the prediction score using real-world data (RWD). Methods. We identified patients in the Corrona RA registry who used TCZm (n = 452), and matched the design and patients from 4 RCTs used in previous work (n = 853). Patients were followed to determine remission status at 24 weeks. We compared the performance of remission prediction models in RWD, first based on variables determined in our prior work in RCTs, and then using an extended variable set, comparing logistic regression and random forest models. We included patients on other biologic disease-modifying antirheumatic drug monotherapies (bDMARDm) to improve prediction. Results. The fraction of patients observed reaching remission on TCZm by their follow-up visit was 12% (n = 53) in RWD vs 15% (n = 127) in RCTs. Discrimination was good in RWD for the risk score developed in RCTs, with area under the receiver-operating characteristic curve (AUROC) of 0.69 (95% CI 0.62-0.75). Fitting the same logistic regression model to all bDMARDm patients in the RWD improved the AUROC on held-out TCZm patients to 0.72 (95% CI 0.63-0.81). Extending the variable set and adding regularization further increased it to 0.76 (95% CI 0.67-0.84). Conclusion. The remission prediction scores, derived in RCTs, discriminated patients in RWD about as well as in RCTs. Discrimination was further improved by retraining models on RWD.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kirurgi (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Surgery (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Reumatologi och inflammation (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Rheumatology and Autoimmunity (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kardiologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)

Keyword

Disease-modifying antirheumatic drug
Machine learning
Prediction model
Rheumatoid arthritis
Remission

Publication and Content Type

art (subject category)
ref (subject category)

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By the author/editor: Johansson, Fredr ...; Collins, Jamie; Yau, Vincent; Guan, Hongshu; Kim, Seoyoung C.; Losina, Elena; show more...; Sontag, D.; Stratton, Jackly ...; Trinh, Huong; Greenberg, Jeffr ...; Solomon, Daniel ...; show less...

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Surgery

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Rheumatology and ...

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Cardiac and Card ...

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By the university: Chalmers University of Technology

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