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Predictors of Treatment Change Among Patients with Rheumatoid Arthritis Treated with TNF Inhibitors as First-Line Biologic Agent in the USA: A Cohort Study from Longitudinal Electronic Health Records

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Abstract

Background

Previous observational studies utilizing administrative claims data have largely been unable to consider clinical factors that may be related to patterns of drug use among patients with rheumatoid arthritis (RA).

Objective

To understand predictors of treatment changes following initiation of a tumor necrosis factor inhibitor (TNFi) using nation-wide electronic health record (EHR) data in the USA.

Methods

The Optum Immunology Condition EHR data (01/01/2011–09/30/2019) was used to identify a population of adult patients with RA initiating a TNFi as the first line biologic disease-modifying anti-rheumatic drug (DMARD). The primary outcome was any treatment change during the 1-year post-index period defined as cycling to a different TNFi or switching to non-TNFi biologic or targeted synthetic DMARDs. Secondary outcomes were the individual components of TNFi cycling and switching, examined separately. To identify predictors of DMARD treatment changes, we used a least absolute shrinkage and selection operator (LASSO) regression model. Model c-statistics and odds ratios (ORs, 95% confidence intervals (CIs)) of predictors were reported.

Results

We identified 24,871 patients with RA who initiated a TNFi. The mean age was 55.5 (± 13.7) years and 77.2% were female. Among the TNFi initiators, 22.2% experienced TNFi cycling or switching during the 1-year follow-up time. Predictors that are associated with higher likelihood of TNFi cycling or switching included female gender (OR: 1.26, 95% CI: 1.16–1.36) and glucocorticoid use (OR: 1.30, 95% CI: 1.21–1.40). In contrast, inflammatory bowel disease (OR: 0.62, 95% CI: 0.48–0.78), psoriasis (OR: 0.82, 95% CI: 0.70–0.95), recent use of methotrexate (OR: 0.89, 95% CI: 0.81–0.97), and vitamin D intake (OR: 0.92, 95% CI: 0.85–0.99) were negatively associated with TNFi cycling or switch.

Conclusions

Gender, glucocorticoid use, inflammatory bowel disease, psoriasis, and vitamin D intake were identified as significant predictors of TNFi cycling or switching for TNFi initiators in the RA population. Predicting treatment change remains challenging even with large detailed EHR data.

Plain Language Summary

This study aimed to identify key determinants of treatment changes among patients with rheumatoid arthritis (RA) initiating a tumor necrosis factor inhibitor (TNFi) as their first-line biologic disease-modifying antirheumatic drug (DMARD) in routine care settings using a US nation-wide longitudinal electronic health record (EHR). Among 24,871 patients with RA who initiated a TNFi, 22.2% experienced TNFi cycling or switching during the 1-year follow-up time. Female patients and those who used glucocorticoids were more likely to experience TNFi cycling or switching, whereas inflammatory bowel disease, psoriasis, recent methotrexate use, and vitamin D intake were negatively associated with the outcome. However, predicting treatment change remains challenging even with larger detailed EHR data potentially due to unmeasured factors such as prescriber’s preference or patient’s belief in the medication.

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Authors and Affiliations

  1. Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women’s Hospital and Harvard Medical School, 1620 Tremont Street, Suite 3030, Boston, MA, 02120, USA

    Yinzhu Jin, Joan E. Landon, Rishi J. Desai & Seoyoung C. Kim

  2. AbbVie Global Epidemiology, Pharmacovigilance and Patient Safety, North Chicago, IL, USA

    Whitney Krueger & Alexander Liede

  3. Division of Rheumatology, Inflammation, and Immunity, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA

    Seoyoung C. Kim

Authors
  1. Yinzhu Jin
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  2. Joan E. Landon
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  3. Whitney Krueger
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  4. Alexander Liede
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  5. Rishi J. Desai
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  6. Seoyoung C. Kim
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Corresponding author

Correspondence to Seoyoung C. Kim.

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Funding

This project was supported by AbbVie (grant number: 2018A018586).

Role of the study sponsor

The sponsor provided the data access to the authors at Brigham and Women’s Hospital via the third-party agreement. The authors at Brigham and Women’s Hospital analyzed the data, interpreted the results, determined the final wording of the manuscript, and had the final decision to submit the manuscript for publication. The sponsor was given the opportunity to make nonbinding comments on a draft of the manuscript. Publication of this article was not contingent upon approval by the sponsor.

Conflicts of interest/Competing interests

Jin and Landon declare that they have no conflict of interest. Desai reports receiving research grants from Bayer, Vertex, and Novartis for unrelated research. Liede and Krueger are full-time AbbVie employees and therefore own AbbVie stock. Kim has received research grants to the Brigham and Women’s Hospital from Pfizer, AbbVie, Roche and Bristol-Myers Squibb.

Availability of data and material

The data that support the findings of this study are not publicly available.

Code availability

The codes that support the findings of this study are available from the corresponding author, SCK, upon reasonable request.

Authors' contributions

All authors meet the journal’s criteria for authorship. All authors have contributed to the work and approve the presented findings.

Ethics approval

The study protocol was reviewed and approved by the Institutional Review Board (IRB) of the Brigham and Women’s Hospital (IRB protocol number: 2019P003604).

Consent to participate

Patient-informed consent was not required, since the data were deidentified.

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Not applicable.

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Jin, Y., Landon, J., Krueger, W. et al. Predictors of Treatment Change Among Patients with Rheumatoid Arthritis Treated with TNF Inhibitors as First-Line Biologic Agent in the USA: A Cohort Study from Longitudinal Electronic Health Records. BioDrugs 36, 521–535 (2022). https://doi.org/10.1007/s40259-022-00542-w

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