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Treatment sequences and lines of therapy in rheumatoid arthritis: a real-world evaluation of retention and effectiveness


1, 2, 3, 4, 5, 6, 7

 

  1. UHN, Toronto General Hospital Research Institute, Toronto, and Institute of Health Policy, Management and Evaluation (IHPME), University of Toronto, Canada. mohammad.movahedi@uhn.ca
  2. Department of Medicine, Division of Rheumatology, University of Toronto, Canada.
  3. UHN, Toronto General Hospital Research Institute, Toronto, Canada.
  4. UHN, Toronto General Hospital Research Institute, Toronto, Canada.
  5. Ottawa Hospital Research Institute, Ottawa, Canada.
  6. UHN, Toronto General Hospital Research Institute, Toronto; Institute of Health Policy, Management and Evaluation (IHPME), University of Toronto; and Department of Medicine, University of Toronto, Canada.
  7. Department of Medicine, Division of Rheumatology, University of Toronto, and Department of Medicine, University of Toronto, Canada.

on behalf of Ontario Best Practices Initiative (OBRI) Investigators, UHN, Toronto, Canada.

CER19038
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PMID: 41231429 [PubMed]

Received: 23/06/2025
Accepted : 13/10/2025
In Press: 12/11/2025

Abstract

OBJECTIVES:
Many patients with rheumatoid arthritis (RA) do not maintain disease control or tolerance their first advanced therapy (AT), making subsequent treatment choices critical. This study described real-world patterns of sequential AT use and evaluate drug survival and effectiveness across multiple lines of therapy in a large Canadian RA cohort. METHOSD: Adult RA patients from the Ontario Best Practice Research Initiative (OBRI) who initiated AT between 2008 and 2023 were included. Drug survival was defined as time from initiation to discontinuation. Effectiveness was assessed using changes in Clinical Disease Activity Index (CDAI), achievement of minimal clinically important difference (MCID), low disease activity (LDA), and remission at 6 months. Outcomes were compared before and after 2010, the year treat-to-target (T2T) guidelines were introduced. Analyses were adjusted using propensity scores and multiple imputation for missing data.
RESULTS:
Among 2,449 patients, TNFi agents were the most common first-line AT. Drug survival decreased with each subsequent line. Patients initiating AT after 2010 had shorter treatment durations (median 7.63 vs. 12.2 years), reflecting more frequent switching under T2T strategies. First-line therapies showed greater CDAI improvement and higher MCID, LDA, and remission rates. Effectiveness declined in later lines but remained clinically meaningful.
CONCLUSIONS:
This study offers insights into real-world sequential AT use in Canadian RA care. First-line AT is associated with superior survival and effectiveness; however, subsequent therapies continue to provide important clinical benefits. These findings support the value of personalised sequential treatment strategies and highlight the need for further research to inform future RA management guidelines.

DOI: https://doi.org/10.55563/clinexprheumatol/y1vbr1

Rheumatology Article

Rheumatology Addendum