Predicting Loss of Remission in RA Treated With Etanercept-Methotrexate

Investigators sought to determine which characteristics are predictive of remission induction and subsequent loss of remission in patients with moderately active RA.

Targeting sustained and strictly-defined clinical remission in patients with moderately active rheumatoid arthritis (RA) who are receiving etanercept plus methotrexate before considering dose or regimen modifications may help to improve the likelihood that a patient will remain in clinical remission, according to the results of the PRESERVE study ( identifier: NCT00565409) published in Arthritis Research & Therapy.

The investigators sought to evaluate which characteristics are predictive of remission induction and subsequent loss of remission in patients with moderately active RA (defined as Disease Activity Score in 28 joints [DAS28} >3.2 and ≤5.1) being treated with etanercept plus methotrexate induction therapy for 36 weeks, followed by either reduced-dose etanercept or etanercept withdrawal.

In this open-label phase of the study, patients with week-36 DAS28/Simplified Disease Activity Index (SDAI)/Clinical Disease Activity Index (CDAI) values were included in the analysis. Remission was defined as DAS28 <2.6, SDAI ≤3.3, and CDAI ≤2.8 after 36 weeks of full-dose combination therapy.

Those patients who attained DAS28 low disease activity at 36 weeks were then randomly assigned to double-blinded treatment with etanercept 50 mg once weekly plus methotrexate, etanercept 25 mg once weekly plus methotrexate, or placebo plus methotrexate, all for 52 weeks.

Younger age, body mass index (BMI) <30 kg/m2, and lower Health Assessment Questionnaire scores at baseline were all significantly predictive of week 36 remission (P <.05), based on DAS28, SDAI, and CDAI values. Moreover, baseline DAS28, SDAI, and CDAI were all significant predictors of all 3 remission endpoints (P <.05).

The strongest predictors of loss of DAS28 remission among all 3 treatment groups included the following: failure to achieve sustained remission (DAS28 <2.6 at 12, 20, 28, and 36 weeks) with induction therapy, higher DAS28/SDAI/CDAI at randomization and at 1 month, increase in DAS28/SDAI/CDAI values at 1 month, and increase in DAS28/SDAI/CDAI components and patient-reported outcomes at 1 month.

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There were similar significant predictors reported for loss of SDAI and CDAI remission, with the exception of not achieving sustained remission.

The investigators concluded that patients who are younger and have lower BMI, lower Health Assessment Questionnaire scores, and lower disease activity at baseline are most likely to achieve remission when treated with etanercept plus methotrexate combination induction therapy.

In addition, those who do not achieve sustained remission with induction therapy, as well as those with worse disease activity and patient-reported outcomes early on after receiving maintenance therapy, are most likely to lose remission. The results of this study may help guide decision-making among clinicians with respect to treating patients with RA.


Smolen JS, Szumski A, Koenig AS, Jones TV, Marshall L. Predictors of remission with etanercept-methotrexate induction therapy and loss of remission with etanercept maintenance, reduction, or withdrawal in moderately active rheumatoid arthritis: results of the PRESERVE trial. Arthritis Res Ther. 2018;20(1):8.