Study of RA Remission Predictors Supports Treat-to-Target Approach to Combination Etanercept Therapy

Targeting sustained and stringently defined clinical remission in patients with moderately active rheumatoid arthritis (RA) receiving full-dose combination therapy with etanercept plus methotrexate before considering dose or regimen changes may help improve the likelihood that patients will remain in clinical remission 1 year after changes are made, according to a new analysis of data from the 2013 PRESERVE trial.

Patients with moderately active RA who are younger and have a lower body mass index (BMI), a lower Health Assessment Questionnaire (HAQ) score, and lower disease activity at baseline are more likely to achieve remission when receiving combination etanercept and methotrexate induction therapy, Josef S. Smolen, MD, and colleagues concluded. The researchers said their findings, reported in the January 16, 2018, issue of Arthritis Research & Therapy, may provide important information needed to help guide clinicians’ decision making as they treat patients to remission and beyond.

Smolen and colleagues also report that patients with RA who fail to achieve sustained remission with induction therapy, and those with worse disease activity and patient-reported outcomes (PROs) early after initiating maintenance therapy with a full-dose or reduced-dose etanercept-methotrexate regimen or methotrexate monotherapy, were most likely to lose remission across all treatment arms of the original PRESERVE trial.

The PRESERVE trial was an induction/maintenance study of etanercept that assessed the consequences of etanercept dose reduction or withdrawal in approximately 600 adults with moderately active RA who achieved low disease activity (LDA) after 36 weeks of treatment with full-dose etanercept combined with methotrexate. The current study presents post-hoc analyses of PRESERVE data to identify potential predictive markers for remission induction and loss after modification of etanercept dosing. It uses Disease Activity Score in 28 joints (DAS28), based on erythrocyte sedimentation rate (ESR) less than 2.6 to indicate remission, as well as American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) remission criteria including the Simplified Disease Activity Index (SDAI) and Clinical Disease Activity Index (CDAI).

The data in the current report reveal that a large proportion of patients with moderate RA were able to achieve DAS28 remission with full-dose combination etanercept-plus-methotrexate therapy by the end of the open-label period of the PRESERVE study. However, withdrawal of etanercept after achievement of response resulted in a loss of remission in many patients in the double-blind period of the study.

These findings indicate that depth of disease control is an important predictor of remission loss, the researchers said. “This result underscores and reinforces the current treat-to-target approach and the importance of adjusting treatment in patients who are not achieving the lowest levels of disease activity currently recommended in ACR/EULAR treatment guidelines, as it suggests that the depth and duration of response are relevant,” they stress. “Predictors identified for the maintenance of SDAI and CDAI remission (with the exception of failure to achieve sustained SDAI or CDAI) further support the conclusion of a better outcome with lower disease activity and maintenance of a good response at the time of withdrawal.”