Effectiveness of Methotrexate and Bridging Glucocorticoids with or Without Early Introduction of a 6-month Course of Etanercept in Early RA: Results of the 2-year, Pragmatic, Randomised CareRA2020 Trial

Overview

Journal RMD Open

Publisher BMJ Publishing Group

Specialty Rheumatology

Date 2024 Aug 8

PMID 39117445

Authors

Delphine Bertrand

Johan Joly

Barbara Neerinckx

Patrick Durez

Jan Lenaerts

Rik Joos

Kristof Thevissen

Tom Zwaenepoel

Johan Vanhoof

Silvana Di Romana

Veerle Taelman

Els Van Essche

Luk Corluy

Clio Ribbens

Marc Vanden Berghe

Mieke Devinck

Sofia Ajeganova

Anne Durnez

Yves Boutsen

Joelle Margaux

Isabelle Peene

Jan Van Offel

Michael Doumen

Sofia Pazmino

Elias De Meyst

Myroslava Kulyk

Nelly Creten

Rene Westhovens

Patrick Verschueren

Affiliations

Soon will be listed here.

Abstract

Objectives: To investigate if patients with early rheumatoid arthritis responding insufficiently to initial methotrexate (MTX) and bridging glucocorticoids (GCs) could benefit from early but temporary etanercept introduction as a second remission-induction attempt.

Methods: CareRA2020 (NCT03649061) was a 2-year, open-label, multicentre, pragmatic randomised controlled trial. Treatment-naïve patients started MTX and GC bridging (COBRA-Slim: CS). Within a time window from week (W) 8 until W32, early insufficient responders (28-joint Disease Activity Score - C-reactive Protein (DAS28-CRP) >3.2 between W8 and W32 or ≥2.6 at W32) were randomised to a Standard-CS strategy (adding leflunomide first) or Bio-induction-CS strategy (adding etanercept for 24 weeks). Additional treatment adaptations followed the treat-to-target principle. Longitudinal disease activity (DAS28-CRP) over 104 weeks (primary outcome), achievement of DAS28-CRP <2.6 28 weeks after randomisation, and biologic or targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD) use at W104 were compared between randomisation groups.

Results: Following CS treatment, 142 patients were early responders; 55 early insufficient responders received Standard-CS and 55 Bio-induction-CS. Superiority of Bio-induction-CS over Standard-CS could not be demonstrated (ß=-0.204, (95% CI -0.486 to 0.078), p=0.157) for the primary outcome. More patients on Bio-induction-CS achieved DAS28-CRP <2.6 at 28 weeks after randomisation (59% (95% CI 44% to 72%) vs 44% (95% CI 31% to 59%) in Standard-CS) and they were treated less frequently with b/tsDMARDs at W104 (19/55, 35%) compared with Standard-CS (29/55, 53%).

Conclusion: Half of the patients responded well to initial COBRA-Slim induction therapy. In early insufficient responders, adding etanercept for 6 months did not improve disease control over 104 weeks versus adding leflunomide first. However, temporary introduction of etanercept resulted in improved disease control early after randomisation and less patients on b/tsDMARDs at W104.

Trial Registration Number: NCT03649061.

Ctr Pilot Approval Belgium: S59474, EudraCT number: 2017-004054-41.

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