Failed Remission in Early RA No Better With Added Etanercept

TOPLINE:

Treatment with etanercept led to faster disease control initially in patients with early rheumatoid arthritis (RA) who had an insufficient early response to methotrexate and bridging glucocorticoids therapy, but more patients achieved disease control with leflunomide at 104 weeks.

METHODOLOGY:

• Researchers conducted CareRA2020, a randomized controlled trial including 276 patients with early RA who were initially treated with oral methotrexate 15 mg/wk and a step-down prednisone scheme, with early insufficient responders (n = 110) randomized to add etanercept 50 mg/wk or leflunomide 10 mg/d for 24 weeks.
• Patients were classified as early insufficient responders if they did not achieve a 28-joint Disease Activity Score with C-reactive protein (DAS28-CRP) < 3.2 between weeks 8 and 32 or < 2.6 at week 32, despite an increase in methotrexate dose to 20 mg/wk.
• The primary outcome was the longitudinal disease activity measured by DAS28-CRP over 104 weeks.
• The secondary outcomes included disease control at 28 weeks post-randomization and the use of biologic or targeted synthetic disease-modifying antirheumatic drugs at week 104.

TAKEAWAY:

• Early introduction of etanercept in patients with RA did not show long-term superiority over leflunomide in disease control over 2 years (P = .157).
• At 28 weeks post-randomization, the percentage of patients who achieved a DAS28-CRP < 2.6 was higher in the etanercept group than in the leflunomide group (59% vs 44%).
• After stopping etanercept, disease activity scores worsened, and a lower proportion of patients achieved DAS28-CRP < 2.6 in the etanercept group than in the leflunomide group (55% vs 69%) at week 104.
• Even after treatment with etanercept or leflunomide, the 110 early insufficient responders never reached the same level of disease control as the 142 patients who responded to methotrexate and bridging glucocorticoids within weeks 8-32.

IN PRACTICE:

“The CareRA2020 trial did not completely solve the unmet need of patients responding insufficiently to conventional initial therapy for early RA, but it provides opportunities to further optimize the treatment approach in this population, for instance, by focusing on the identification of potential subgroups with different disease activity trajectories within the early insufficient responder group,” wrote the authors.

SOURCE:

The study was led by Delphine Bertrand of the Skeletal Biology and Engineering Research Center in the Department of Development and Regeneration at KU Leuven, Leuven, Belgium, and was published online on August 7, 2024, in RMD Open.

LIMITATIONS:

The open-label design of the study may have introduced bias, as patients and investigators were aware of the treatment. The temporary administration of etanercept may not have reflected its long-term effects. The study was conducted in Belgium, which limited the generalizability of the findings to other populations.

DISCLOSURES:

The study was supported by the Belgian Health Care Knowledge Centre. Some authors reported serving as speakers or receiving grants, consulting fees, honoraria, or meeting or travel support from financial ties with Novartis, Pfizer, Amgen, and other pharmaceutical companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.