Predictors of Remission Maintenance after Etanercept Tapering or Withdrawal in Early Rheumatoid Arthritis: Results from the PRIZE Study

Objective: To explore the influence of early treatment response to etanercept-methotrexate therapy on sustained remission after tapering/withdrawal of etanercept in methotrexate/biologic-naive patients with early rheumatoid arthritis in the PRIZE study (ClinicalTrials.gov: NCT00913458). Method: In the initial 52-week open-label phase, enrolled patients received once-weekly etanercept 50 mg plus methotrexate. Patients who achieved DAS28 ≤3.2 at week 39 and <2.6 at week 52 were randomized to etanercept 25 mg plus methotrexate, methotrexate monotherapy, or placebo once weekly for 39 weeks in the double-blind phase. The relationships between responses in the open-label phase and sustained remission (DAS28 <2.6 at weeks 76 and 91, without glucocorticoid rescue therapy from weeks 52 to 64) in the double-blind phase were analyzed. Results: In the open-label phase, 70% of patients achieved DAS28 remission at week 52. In the double-blind phase, 63%, 40%, and 23% of patients had sustained DAS28 remission in the reduced-dose combination-therapy, methotrexate-monotherapy, and placebo groups, respectively. In patients receiving reduced-dose combination therapy, sustained remission was more likely in those who achieved DAS28 remission (p = 0.005) or low disease activity (p=0.044) in a shorter time, and who had a lower DAS28 (p = 0.016) or achieved ACR/EULAR Boolean remission (p < 0.05) at the end of the open-label phase. In patients receiving methotrexate monotherapy, sustained remission was associated with a lower acute-phase response (C-reactive protein, p = 0.007; erythrocyte sedimentation rate, p = 0.016) at the end of the open-label phase. Conclusion: Fast response and suppression of inflammation with etanercept-methotrexate therapy may predict successful etanercept tapering/withdrawal in patients with early rheumatoid arthritis.