Sustained remission with etanercept tapering in early rheumatoid arthritis

N Engl J Med. 2014 Nov 6;371(19):1781-92. doi: 10.1056/NEJMoa1316133.


Background: We assessed the effects of reduction and withdrawal of treatment in patients with rheumatoid arthritis who had a remission while receiving etanercept-plus-methotrexate therapy.

Methods: Patients with early active disease who had not previously received methotrexate or biologic therapy received 50 mg of etanercept plus methotrexate weekly for 52 weeks (open-label phase). We then randomly assigned patients who had qualifying responses at weeks 39 and 52 to receive 25 mg of etanercept plus methotrexate (combination-therapy group), methotrexate alone, or placebo for 39 weeks (double-blind phase). Patients who had qualifying responses at week 39 of the double-blind phase had all treatment withdrawn at that time and were followed to week 65 (treatment-withdrawal phase). The primary end point was the proportion of patients with sustained remission in the double-blind phase.

Results: Of 306 patients enrolled, 193 underwent randomization in the double-blind phase; 131 qualified for the treatment-withdrawal phase. More patients in the combination-therapy group than in the methotrexate-alone group or the placebo group met the criterion for the primary end point (40 of 63 [63%] vs. 26 of 65 [40%] and 15 of 65 [23%], respectively; P=0.009 for combination therapy vs. methotrexate alone; P<0.001 for combination therapy vs. placebo). At 65 weeks, 28 patients (44%) who had received combination therapy, 19 (29%) who had received methotrexate alone, and 15 (23%) who had received placebo were in remission (P=0.10 for combination therapy vs. methotrexate alone; P=0.02 for combination therapy vs. placebo; P=0.55 for methotrexate alone vs. placebo). No significant between-group differences were observed in radiographic progression of disease. Serious adverse events were reported in 3 patients (5%) in the combination-therapy group, 2 (3%) in the methotrexate-alone group, and 2 (3%) in the placebo group.

Conclusions: In patients with early rheumatoid arthritis who had a remission while receiving full-dose etanercept-plus-methotrexate therapy, continuing combination therapy at a reduced dose resulted in better disease control than switching to methotrexate alone or placebo, but no significant difference was observed in radiographic progression. (Funded by Pfizer; number, NCT00913458.).

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antirheumatic Agents / administration & dosage*
  • Antirheumatic Agents / adverse effects
  • Arthritis, Rheumatoid / drug therapy*
  • Double-Blind Method
  • Drug Therapy, Combination
  • Etanercept
  • Female
  • Humans
  • Immunoglobulin G / administration & dosage*
  • Immunoglobulin G / adverse effects
  • Infections / etiology
  • Male
  • Methotrexate / administration & dosage*
  • Methotrexate / adverse effects
  • Middle Aged
  • Receptors, Tumor Necrosis Factor / administration & dosage*
  • Remission Induction
  • Withholding Treatment


  • Antirheumatic Agents
  • Immunoglobulin G
  • Receptors, Tumor Necrosis Factor
  • Etanercept
  • Methotrexate

Associated data