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Abstract
Objectives To compare outcomes of different treatment schedules from the care in early rheumatoid arthritis (CareRA) trial over 5 years.
Methods Patients with RA completing the 2-year CareRA randomised controlled trial were eligible for the 3-year observational CareRA-plus study. 5-year outcomes after randomisation to initial methotrexate (MTX) monotherapy with glucocorticoid bridging (COBRA-Slim) were compared with MTX step-up without glucocorticoids or conventional synthetic disease-modifying antirheumatic drug (DMARD) combinations with glucocorticoid bridging, per prognostic patient group. Disease activity (Disease Activity Score based on 28 joints calculated with C reactive protein (DAS28-CRP)) and functionality (Health Assessment Questionnaire (HAQ)) were compared between treatment arms using longitudinal models; safety and drug use were detailed.
Results Of 322 eligible patients, 252 (78%) entered CareRA-plus, of which 203 (81%) completed the study. Treatments for high-risk patients resulted in comparable DAS28-CRP (p=0.539) and HAQ scores over 5 years (p=0.374). Low-risk patients starting COBRA-Slim had lower DAS28-CRP (p<0.001) and HAQ scores (p=0.041) than those starting only on MTX. At study completion, 114/203 (56%) patients never had their original DMARD therapy intensified, with comparable rates between all treatments. Safety was comparable between treatments in high-risk patients. In low-risk patients, there were 18 adverse events in 10 COBRA-Slim and 36 in 17 patients treated with initial MTX monotherapy (p=0.048). Over 5 years, 22% of patients initiated biologics, 25% took glucocorticoids for >3 months and 17% for >6 months outside the bridging period.
Conclusions All intensive treatments with glucocorticoids bridging demonstrated excellent 5 year outcomes. Initiating COBRA-Slim was comparably effective as more complex treatments for high-risk patients with early RA and more effective than initial MTX monotherapy for low-risk patients with limited need for biologics and chronic glucocorticoid use.
- glucocorticoids
- arthritis
- rheumatoid
- biological therapy
- methotrexate
- outcome assessment
- health care
Data availability statement
Data are available upon reasonable request. The authors commit to making the relevant anonymised patient level data available for a specified purpose approved by the institution and the principal investigator of the CareRA plus study and with a signed data access agreement.
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Data availability statement
Data are available upon reasonable request. The authors commit to making the relevant anonymised patient level data available for a specified purpose approved by the institution and the principal investigator of the CareRA plus study and with a signed data access agreement.
Footnotes
Handling editor Josef S Smolen
Twitter @sophie_33pl, @DiederikDeCock
Contributors PV, JJ and RW designed the study protocol in collaboration with the CareRA study group. Investigators of the CareRA study group, including PV and RW recruited and enrolled patients and were responsible for daily patient management. PV, VS and JJ were responsible for coordination of the trial and of collection of data. VS was responsible for data analysis. All authors contributed to interpretation of the data. Furthermore, VS, PV, DDC and RW drafted the manuscript. SP, KVdE, DB and JJ revised it critically for important intellectual content. All authors have approved the final draft for publication. PV and VS are the guarantors.
Funding The CareRA RCT was supported by a grant from the Flemish Governmental Agency for Innovation by Science and Technology (IWT). PV holds the unrestricted Pfizer Chair for ‘Early Rheumatoid Arthritis Management’ at the KU Leuven. Leflunomide was made available for CareRA for free by SANOFI Belgium without any influence on trial design.
Disclaimer The funders had no role in study design, data collection, analysis and interpretation or reporting of this study. Patrick Verschueren and Veerle Stouten affirm that this manuscript is an honest, accurate, and transparent account of the study being reported.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
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