Study Comparing Etanercept in Combination With Methotrexate in Subjects With Rheumatoid Arthritis (PRESERVE)

• Proportion of subjects achieving low disease activity or remission at each visit during period 1 and period 2. [ Time Frame: Week 1 to Week 88 ] [ Designated as safety issue: No ]
• Change in the DAS28 during period 1 and period 2 at each visit. [ Time Frame: Week 1 to Week 88 ] [ Designated as safety issue: No ]
• Time to loss of low disease activity (DAS28 >3.2) and a change of ≥0.6 in the DAS28 during period 2. [ Time Frame: Week 36 to Week 88 ] [ Designated as safety issue: No ]
• Time to loss of low disease activity (DAS28 >3.2) during period 2. [ Time Frame: Week 36 to Week 88 ] [ Designated as safety issue: No ]
• Proportion of time subjects have low disease activity. [ Time Frame: Week 1 to Week 88 ] [ Designated as safety issue: No ]
• Change in the painful and swollen joint counts during period 1 and period 2 at each visit. [ Time Frame: Week 1 to Week 88 ] [ Designated as safety issue: No ]
• Change in the physician global assessments during period 1 and period 2 at each visit. [ Time Frame: Week 1 to Week 88 ] [ Designated as safety issue: No ]
• Change in the subject global assessments, including morning stiffness (measured in minutes), during period 1 and period 2 at each visit. [ Time Frame: Week 1 to Week 88 ] [ Designated as safety issue: No ]
• Change in the general health Visual Analog Scale (VAS), and pain VAS during period 1 and period 2 at each visit. [ Time Frame: Week 1 to Week 88 ] [ Designated as safety issue: No ]
• Proportion of subjects achieving an acceptable state on the Patient Acceptable Symptom State (PASS) at various visits. [ Time Frame: Week 1, 36, 64 and 88 ] [ Designated as safety issue: No ]
• Proportion of subjects achieving European League Against Rheumatism (EULAR) good or moderate responses during period 1 and period 2 at each visit. [ Time Frame: Week 1 to Week 88 ] [ Designated as safety issue: No ]
• Proportion of subjects achieving American College of Rheumatology (ACR) 20, ACR 50, ACR 70 and ACR 90 during period 1 and period 2 at each visit. [ Time Frame: Week 1 to Week 88 ] [ Designated as safety issue: No ]

To compare the efficacy of the combination of etanercept 50 mg once weekly plus methotrexate with that of methotrexate monotherapy in the treatment of rheumatoid arthritis over 88 weeks.

• Drug: Etanercept
  Subcutaneous (SC), 50 mg, once weekly for 88 weeks
  Other Name: Enbrel
• Drug: Methotrexate

  Oral, 15 to 25 mg (varying based on dosage the subject is receiving at the time of screening and may be increased at the discretion of the investigator through Week 28 to a maximum of 25 mg/week), once weekly for 88 weeks.

  If a subject experiences an adverse event (AE) during the study, Methotrexate may be decreased by 2.5 or 5.0 mg weekly (the minimum dose to stay in the study is 10 mg/week).

• Drug: Etanercept
  Subcutaneous (SC), 25 mg, once weekly from week 36 to week 88.
• Drug: Placebo
  Subcutaneous (SC), once weekly from week 36 to week 88.

• Active Comparator: 1
  Interventions:

  • Drug: Etanercept
  • Drug: Methotrexate
• Active Comparator: 2
  Interventions:

  • Drug: Etanercept
  • Drug: Methotrexate
• Placebo Comparator: 3
  Interventions:

  • Drug: Placebo
  • Drug: Methotrexate

Inclusion Criteria:

• Diagnosis of rheumatoid arthritis.
• Currently receiving an optimal dose of oral Methotrexate (MTX)(at least 15 mg/week but no more than 25 mg/week) for the treatment of rheumatoid arthritis.
• Active rheumatoid arthritis at the time of screening.

Exclusion Criteria:

• Previous or current treatment with etanercept, other tumor necrosis factor-alpha (TNF) inhibitors, or other biologic agents.
• Concurrent treatment with any disease-modifying anti-rheumatoid drugs (DMARD), other than MTX within 28 days before baseline.
• Concurrent treatment with more than 1 non-steroid anti-inflammatory drug (NSAID) at baseline.