Study Conducted in Subjects With Rheumatoid Arthritis Who Have Moderate to Severe Disease Activity Despite Methotrexate Therapy With or Without Other Non Biologic Disease Modifying Antirheumatic Drugs (DMARDs)for at Least 12 Weeks Prior to Screening

A Randomized, Double-blind Placebo-controlled Study Of The Maintenance Of Efficacy Of Etanercept Plus Dmard(s) Compared With Dmard(s) Alone In Subjects With Rheumatoid Arthritis After Achieving An Adequate Response With Etanercept Plus Dmard(s)

Status

Completed

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01578850

Enrollment

491

Registered

2012-04-17

Start date

2012-07-31

Completion date

2015-03-31

Last updated

2016-07-06

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Rheumatoid Arthritis

Keywords

rheumatoid arthritis, etanercept, methotrexate, DMARDs

Brief summary

To compare the maintenance of efficacy of the combination of etanercept 50 mg once weekly plus methotrexate with or without other disease modifying antirheumatic drugs therapy with that of methotrexate with or without other disease modifying antirheumatic drugs therapy at Week 52 in subjects with moderately to severely active rheumatoid arthritis who have achieved low disease activity after 24 weeks of therapy with open label etanercept 50 mg once weekly plus MTX with or without other disease modifying antirheumatic drugs therapy.

Interventions

DRUGEtanercept

etanercept 50mg once weekly + methotrexate with or without other DMARDs

DRUGplacebo

etanercept placebo once weekly + methotrexate with or without other DMARDs

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to 70 Years

Healthy volunteers

Inclusion criteria

1. Subject has a minimum 1 year history/diagnosis of rheumatoid arthritis based on the 1987 American College of Rheumatology (ACR) Revised criteria for RA. 2. Subject must have active rheumatoid arthritis despite methotrexate (MTX) therapy of ≥10 mg/wk for at least 12 weeks. The MTX dose must be stable for at least 4 weeks immediately prior to screening.

Exclusion criteria

1. Subjects who used any of the following systemic treatments during the washout periods given below: 1. Oral corticosteroid dose of prednisone \>7.5 mg/day (or equivalent) or a change in dose within 28 days of baseline. 2. Treatment with more than 1 NSAID within 14 days at baseline. 3. Methotrexate dose greater than 25 mg/week, or change in the dose of methotrexate within 28 days of baseline. 4. Subjects will be allowed to continue the following non biologic DMARDs: sulfasalazine, hydroxychloroquine, and leflumomide. All other non-biologic DMARDs (including but not limited to gold, penicillamine, azathioprine, cyclophospamide), and biologic DMARDs must have been discontinued at least 2 months prior to Week 1. 5. Any biologic B cell depleting agent (eg, rituximab) within 2 years of Week 1. 2. Receipt of any live (attenuated) vaccine within 4 weeks prior to baseline. 3. Receipt of any live (attenuated) vaccine within 4 weeks prior to baseline.

Design outcomes

Primary

Measure	Time frame	Description
Percentage of Participants Who Remained in Low Disease Activity (LDA) (Disease Activity Score in 28 Joints-erythrocyte Sedimentation Rate [DAS28-ESR] <3.2) at Week 52.	Baseline and Week 52	Proportion of participants who remained in LDA DAS28-ESR \<3.2 at Week 52 is presented below.

Secondary

Measure	Time frame	Description
Change From Baseline in DAS28-CRP and DAS28-ESR in Period 1	Baseline, Weeks 4, 8, 16 and 24	The DAS assessment is a derived measurement with differential weight given to each component. The DAS28-ESR and DAS28-CRP was calculated at every visit within the clinical database in period 1. The components of the DAS28 ESR score assessment are: Tender/ Painful Joint Count (28), Swollen Joint Count (28); ESR, Subject General Health VAS assessment. The components of the DAS28 CRP score assessment were: Tender/Painful Joint Count (28); Swollen Joint Count (28), hsCRP, and the Subject General Health VAS assessment. This efficacy measurement was made at every study visit.
Percentage of Participants Who Remained in Remission at Week 52 (DAS28-ESR)	Baseline and Week 52	Proportion of participants who remained in Remission (DAS28-ESR \<2.6) at Week 52.
Percentage of Participants Achieving LDA (DAS28-ESR and DAS28-C-reactive Protein [CRP]) at Each Visit During Period 1	Baseline, Weeks 4, 8, 16 and 24	Proportion of participants who achieved LDA (DAS28-ESR and DAS28-CRP at each visit during period 1 is presented below.
Percentage of Participants Achieving LDA (DAS28-ESR and DAS28-CRP) at Each Visit During Period 2	Baseline, Weeks 24, 28, 36, 44 and 52	Proportion of participants who achieved LDA (DAS28-ESR and DAS28-CRP at each visit during period 2 is presented below.
Percentage of Participants Achieving Remission (DAS28-ESR and DAS28-CRP) at Each Visit During Period 1	Baseline, Weeks 4, 8, 16 and 24	Proportion of participants who achieved remission (DAS28-ESR and DAS28-CRP at each visit during period 1 is presented below.
Change From Baseline in DAS28-CRP and DAS28-ESR in Period 2	Baseline, Weeks 24, 28, 36, 44 and 52	The DAS assessment is a derived measurement with differential weight given to each component. The DAS28-ESR and DAS28-CRP was calculated at every visit within the clinical database in period 2. The components of the DAS28 ESR score assessment are: Tender/ Painful Joint Count (28), Swollen Joint Count (28); ESR, Subject General Health VAS assessment. The components of the DAS28 CRP score assessment were: Tender/Painful Joint Count (28); Swollen Joint Count (28), hsCRP, and the Subject General Health VAS assessment. This efficacy measurement was made at every study visit.
Percentage of Participants Who Had a Recurrence of Disease Symptoms During Period 2, Based on the Protocol Criteria	Baseline and Week 52	Flare is defined as the criteria of loss of LDA plus ≥0.6 unit worsening in DAS28-ESR score during period 2.
Percentage of Participants Achieving European League Against Rheumatism (EULAR) Good and or Moderate Responses (by Both DAS28-ESR and DAS28-CRP Scores) at Each Visit During Period 1.	Baseline, Weeks 4, 8, 16 and 24	EULAR response is based on DAS28-ESR scores. The following good and moderate response is defined based on DAS28-ESR at endpoint (DAS28-ESR improvement at from Baseline in parenthesis): ≤3.2 units (\>1.2 units) is good response; ≤3.2 units (0.6-1.2 units) are moderate response; ≤3.2 units (≤0.6 units) are no response.
Percentage of Participants Achieving EULAR Good and or Moderate Responses (by Both DAS28-ESR and DAS28-CRP Scores) at Each Visit During Period 2.	Baseline, Weeks 24, 28, 36, 44 and 52	EULAR response is based on DAS28-ESR scores. The following good and moderate response is defined based on DAS28-ESR at endpoint (DAS28-ESR improvement at from Baseline in parenthesis): ≤3.2 units (\>1.2 units) is good response; ≤3.2 units (0.6-1.2 units) are moderate response; ≤3.2 units (≤0.6 units) are no response.
Percentage of Participants Achieving LDA or Remission Based on Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI) at Each Visit During Period 1.	Baseline, Weeks 4, 8, 16 and 24	SDAI and CDAI are defined as: 1\) SDAI = DAS28 prorated Swollen Joint Count (0-28) + DAS28 prorated Tender Joint Count (0-28) + Physician Global Assessment of arthritis (0-10) + Subject Global Assessment of arthritis (0-10) + hs CRP (in mg/dL) in Period 1. 2) CDAI = DAS28 prorated Swollen Joint Count (0-28) + DAS28 prorated Tender Joint Count (0 28) + Physician Global Assessment of arthritis (0-10) + Subject Global Assessment of arthritis (0-10) in Period 1.
Percentage of Participants Achieving LDA or Remission Based on CDAI and SDAI at Each Visit During Period 2.	Baseline, Weeks 24, 28, 36, 44 and 52	SDAI and CDAI are defined as: 1\) SDAI = DAS28 prorated Swollen Joint Count (0-28) + DAS28 prorated Tender Joint Count (0-28) + Physician Global Assessment of arthritis (0-10) + Subject Global Assessment of arthritis (0-10) + hs CRP (in mg/dL) in Period 2. 2) CDAI = DAS28 prorated Swollen Joint Count (0-28) + DAS28 prorated Tender Joint Count (0 28) + Physician Global Assessment of arthritis (0-10) + Subject Global Assessment of arthritis (0-10) in Period 2.
Change of CDAI and SDAI at Each Visit During Period 1.	Baseline, Weeks 4, 8, 16 and 24	SDAI and CDAI are defined as: 1\) SDAI = DAS28 prorated Swollen Joint Count (0-28) + DAS28 prorated Tender Joint Count (0-28) + Physician Global Assessment of arthritis (0-10) + Subject Global Assessment of arthritis (0-10) + hs CRP (in mg/dL) in Period 1. 2) CDAI = DAS28 prorated Swollen Joint Count (0-28) + DAS28 prorated Tender Joint Count (0 28) + Physician Global Assessment of arthritis (0-10) + Subject Global Assessment of arthritis (0-10) in Period 1.
Change of CDAI and SDAI at Each Visit During Period 2	Baseline, Weeks 24, 28, 36, 44 and 52	SDAI and CDAI are defined as: 1\) SDAI = DAS28 prorated Swollen Joint Count (0-28) + DAS28 prorated Tender Joint Count (0-28) + Physician Global Assessment of arthritis (0-10) + Subject Global Assessment of arthritis (0-10) + hs CRP (in mg/dL) in Period 2. 2) CDAI = DAS28 prorated Swollen Joint Count (0-28) + DAS28 prorated Tender Joint Count (0 28) + Physician Global Assessment of arthritis (0-10) + Subject Global Assessment of arthritis (0-10) in Period 2.
Percentage of Participants Achieving Remission (DAS28-ESR and DAS28-CRP) at Each Visit During Period 2	Baseline, Weeks 24, 28, 36, 44 and 52	Proportion of participants who achieved LDA (DAS28-ESR and DAS28-CRP at each visit during period 2 is presented below.
Percentage of Participants Achieving ACR20, ACR50, ACR70 and ACR90 (by 66/68 Joint Counts) During Period 2 at Each Visit.	Baseline, Weeks 24, 28, 36, 44 and 52	A 66 swollen and 68 tender joint count was used for calculating ACR responses. The ACR's definition for calculating improvement in RA (ACR20) was calculated as a 20% improvement in tender and swollen joint counts and 20% improvement in 3 of the 5 remaining ACR core set measures: subject and physician global assessments of arthritis, pain, disability, and an acute phase reactant. Similarly, ACR50, ACR70 and ACR90 were calculated with the respective percent improvement. This efficacy measurement was made at every study visit.
Change in the Tender and Swollen Joint Counts at Each Visit During Period 1 (Using 28 Joint Count as Well as 66/68 Joint Counts).	Baseline, Weeks 4, 8, 16 and 24	A total of 66 swollen and 68 tender joints were assessed for tenderness/pain and swelling by the same qualified personnel (when possible) at each visit. For ACR responses, a 66/68 joint count was used. For DAS28-ESR, Simplified Disease Activity Index (SDAI), and Clinical Disease Activity Index (CDAI) calculations, the 28 joint count was used, which included: shoulders, elbows, wrists, metacarpophalangeal (MCP) joints, proximal interphalangeal (PIP) joints, and knees.
Change in the Tender and Swollen Joint Counts at Each Visit During Period 2 (Using 28 Joint Count as Well as 66/68 Joint Counts).	Baseline, Weeks 24, 28, 36, 44 and 52	A total of 66 swollen and 68 tender joints were assessed for tenderness/pain and swelling by the same qualified personnel (when possible) at each visit. For ACR responses, a 66/68 joint count was used. For DAS28-ESR, Simplified Disease Activity Index (SDAI), and Clinical Disease Activity Index (CDAI) calculations, the 28 joint count was used, which included: shoulders, elbows, wrists, metacarpophalangeal (MCP) joints, proximal interphalangeal (PIP) joints, and knees.
Change in the Physician Global Assessment of Arthritis at Each Visit During Period 1	Baseline, Weeks 4, 8, 16 and 24	The investigator estimated the subject's overall disease activity over the last 2 to 3 days (independent of the Subject Global Assessment of arthritis) using a scale between 0 (no disease activity) and 10 (extreme disease activity) and marking one number with an 'X'.
Change in the Physician Global Assessment of Arthritis at Each Visit During Period 2	Baseline, Weeks 24, 28, 36, 44 and 52	The investigator estimated the subject's overall disease activity over the last 2 to 3 days (independent of the Subject Global Assessment of arthritis) using a scale between 0 (no disease activity) and 10 (extreme disease activity) and marking one number with an 'X'.
Change in the Subject Global Assessment of Arthritis in Period 1	Baseline, Weeks 4, 8, 16 and 24	Subjects assessed their overall disease activity over the last 2 to 3 days using a scale between 0 (no disease activity) and 10 (extreme disease activity), which corresponded to the magnitude of their pain) and marked one number with an 'X'.
Change in the Subject Global Assessment of Arthritis in Period 2	Baseline, Weeks 24, 28, 36, 44 and 52	Subjects assessed their overall disease activity over the last 2 to 3 days using a scale between 0 (no disease activity) and 10 (extreme disease activity), which corresponded to the magnitude of their pain) and marked one number with an 'X'.
Change in Morning Stiffness (Measured in Minutes) at Each Visit During Period 1	Baseline, Weeks 4, 8, 16 and 24	Morning stiffness was defined as stiffness in and around the joints, lasting at least 1 hour before maximal improvement. Participants assessed their overall disease activity over the last 2 to 3 days using a scale between 0 (no disease activity) and 10 (extreme disease activity), which corresponded to the magnitude of their pain) and marked one number with an 'X'.
Change in Morning Stiffness (Measured in Minutes) at Each Visit During Period 2	Baseline, Weeks 24, 28, 36, 44 and 52	Morning stiffness was defined as stiffness in and around the joints, lasting at least 1 hour before maximal improvement. Participants assessed their overall disease activity over the last 2 to 3 days using a scale between 0 (no disease activity) and 10 (extreme disease activity), which corresponded to the magnitude of their pain) and marked one number with an 'X'.
Change in the Subject General Health Visual Analog Scale (VAS) and Pain VAS at Each Visit During Period 1	Baseline, Weeks 4, 8, 16 and 24	Participants were asked to answer the question In general how would you rate your health over the last 2 3 weeks? by marking a vertical line at the appropriate position through the 100 mm VAS. The length on the line was measured from the left (in mm). For Pain VAS, participants assessed the severity of their arthritis pain during the last 2 to 3 days using a 100 mm VAS by marking a vertical line at the appropriate position on the scale between 0 (no pain) and 100 (most severe pain), which corresponded to the magnitude of their pain.
Change in the Subject General Health VAS and Pain VAS at Each Visit During Period 2	Baseline, Weeks 24, 28, 36, 44 and 52	Participants were asked to answer the question In general how would you rate your health over the last 2-3 weeks? by marking a vertical line at the appropriate position through the 100 mm VAS. The length on the line was measured from the left (in mm). For Pain VAS, participants assessed the severity of their arthritis pain during the last 2 to 3 days using a 100 mm VAS by marking a vertical line at the appropriate position on the scale between 0 (no pain) and 100 (most severe pain), which corresponded to the magnitude of their pain.
Change in CRP and ESR at Each Visit During Period 1	Baseline, Weeks 4, 8, 16 and 24	The DAS assessment is a derived measurement with differential weight given to each component. The DAS28-ESR and DAS28-CRP was calculated at every visit within the clinical database in period 1. The components of the DAS28 ESR score assessment are: Tender/ Painful Joint Count (28), Swollen Joint Count (28); ESR, Subject General Health VAS assessment. The components of the DAS28 CRP score assessment were: Tender/Painful Joint Count (28); Swollen Joint Count (28), hsCRP, and the Subject General Health VAS assessment. This efficacy measurement was made at every study visit.
Change in CRP and ESR at Each Visit During Period 2	Baseline, Weeks 24, 28, 36, 44 and 52	The DAS assessment is a derived measurement with differential weight given to each component. The DAS28-ESR and DAS28-CRP was calculated at every visit within the clinical database in period 1. The components of the DAS28 ESR score assessment are: Tender/ Painful Joint Count (28), Swollen Joint Count (28); ESR, Subject General Health VAS assessment. The components of the DAS28 CRP score assessment were: Tender/Painful Joint Count (28); Swollen Joint Count (28), hsCRP, and the Subject General Health VAS assessment. This efficacy measurement was made at every study visit.
Percentage of Participants Achieving American College of Rheumatology (ACR) ACR20, ACR50, ACR70 and ACR90 (by 66/68 Joint Counts) During Period 1 at Each Visit.	Baseline, Weeks 4, 8, 16 and 24	A 66 swollen and 68 tender joint count was used for calculating ACR responses. The ACR's definition for calculating improvement in RA (ACR20) was calculated as a 20% improvement in tender and swollen joint counts and 20% improvement in 3 of the 5 remaining ACR core set measures: subject and physician global assessments of arthritis, pain, disability, and an acute phase reactant. Similarly, ACR50, ACR70 and ACR90 were calculated with the respective percent improvement. This efficacy measurement was made at every study visit.

Countries

Brazil, China, Colombia, Czechia, Egypt, Hungary, Jordan, Lebanon, Malaysia, Mexico, Philippines, Qatar, Romania, Russia, South Africa, Taiwan, Thailand, Ukraine, United Arab Emirates

Participant flow

Recruitment details

The study consisted of Period 1 (an open-label, 24-week treat-to-target period), and Period 2 (a double-blind, randomized, 28-week period for participants who qualified for randomization).

Pre-assignment details

The study was conducted in participants with rheumatoid arthritis (RA) who had moderate to severe disease activity despite methotrexate (MTX) therapy (≥10 mg/week) with or without other non-biologic disease modifying anti-rheumatic drugs (DMARDs) for at least 12 weeks prior to screening.

Participants by arm

Arm	Count
Etanercept Participants were randomized to receive ETN 50 mg QW with MTX (with or without other DMARDs).	167
Placebo Participants were randomized to receive PBO 50 mg QW with MTX (with or without other DMARDs).	176
Total	343

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002
Period 1	Adverse Event	11	0	0
Period 1	Death	1	0	0
Period 1	Does Not Meet Entrance Criteria	12	0	0
Period 1	Insufficient Clinical Response	1	0	0
Period 1	Study Terminated by Sponsor	3	0	0
Period 1	Withdrawal by Subject	9	0	0
Period 2	Adverse Event	0	3	6
Period 2	Insufficient Clinical Response	0	1	0
Period 2	Lost to Follow-up	0	1	2
Period 2	Study Terminated by Sponsor	0	5	4
Period 2	Unspecified Reasons	0	1	0
Period 2	Withdrawal by Subject	0	2	2

Baseline characteristics

Characteristic	Etanercept	Placebo	Total
Age, Continuous	46.2 Years STANDARD_DEVIATION 12.88	47.0 Years STANDARD_DEVIATION 12.02	46.6 Years STANDARD_DEVIATION 12.44
Sex: Female, Male Female	140 Participants	150 Participants	290 Participants
Sex: Female, Male Male	27 Participants	26 Participants	53 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —
other Total, other adverse events	26 / 489	4 / 167	9 / 176
serious Total, serious adverse events	13 / 489	0 / 167	7 / 176

Outcome results

Primary

Percentage of Participants Who Remained in Low Disease Activity (LDA) (Disease Activity Score in 28 Joints-erythrocyte Sedimentation Rate [DAS28-ESR] <3.2) at Week 52.

Proportion of participants who remained in LDA DAS28-ESR \<3.2 at Week 52 is presented below.

Time frame: Baseline and Week 52

Population: The FAS included all randomized participants who met the period 2 DAS28-ESR inclusion criteria, had at least one dose of study drug during Period 2 (ie, ETN, MTX or PBO) and had at least one valid efficacy (DAS28-ESR) evaluation after randomization.

Arm	Measure	Value (NUMBER)
Etanercept	Percentage of Participants Who Remained in Low Disease Activity (LDA) (Disease Activity Score in 28 Joints-erythrocyte Sedimentation Rate [DAS28-ESR] <3.2) at Week 52.	43.6 percentage of participants
Placebo	Percentage of Participants Who Remained in Low Disease Activity (LDA) (Disease Activity Score in 28 Joints-erythrocyte Sedimentation Rate [DAS28-ESR] <3.2) at Week 52.	17.3 percentage of participants

p-value: <0.00195% CI: [16.78, 35.81]Cochran-Mantel-Haenszel

Secondary

Change From Baseline in DAS28-CRP and DAS28-ESR in Period 1

The DAS assessment is a derived measurement with differential weight given to each component. The DAS28-ESR and DAS28-CRP was calculated at every visit within the clinical database in period 1. The components of the DAS28 ESR score assessment are: Tender/ Painful Joint Count (28), Swollen Joint Count (28); ESR, Subject General Health VAS assessment. The components of the DAS28 CRP score assessment were: Tender/Painful Joint Count (28); Swollen Joint Count (28), hsCRP, and the Subject General Health VAS assessment. This efficacy measurement was made at every study visit.

Time frame: Baseline, Weeks 4, 8, 16 and 24

Population: The FAS for Period 1 (Open Label FAS) included all randomized participants who had at least one dose of open label study drug during Period 1 (ie, ETN or MTX).

Arm	Measure	Group	Value (MEAN)	Dispersion
Etanercept	Change From Baseline in DAS28-CRP and DAS28-ESR in Period 1	DAS28-ESR Week 4 (N= 473)	-1.61 units on a scale	Standard Deviation 1.08
Etanercept	Change From Baseline in DAS28-CRP and DAS28-ESR in Period 1	DAS28-CRP Week 4 (N= 465)	-1.61 units on a scale	Standard Deviation 1.05
Etanercept	Change From Baseline in DAS28-CRP and DAS28-ESR in Period 1	DAS28-ESR Week 8 (N= 473)	-2.14 units on a scale	Standard Deviation 1.18
Etanercept	Change From Baseline in DAS28-CRP and DAS28-ESR in Period 1	DAS28-CRP Week 8 (N= 471)	-2.09 units on a scale	Standard Deviation 1.14
Etanercept	Change From Baseline in DAS28-CRP and DAS28-ESR in Period 1	DAS28-ESR Week 16 (N= 473)	-2.62 units on a scale	Standard Deviation 1.26
Etanercept	Change From Baseline in DAS28-CRP and DAS28-ESR in Period 1	DAS28-CRP Week 16 (N= 472)	-2.54 units on a scale	Standard Deviation 1.21
Etanercept	Change From Baseline in DAS28-CRP and DAS28-ESR in Period 1	DAS28-ESR Week 24 (N= 473)	-3.23 units on a scale	Standard Deviation 1.35
Etanercept	Change From Baseline in DAS28-CRP and DAS28-ESR in Period 1	DAS28-CRP Week 24 (N= 472)	-2.95 units on a scale	Standard Deviation 1.27

Secondary

Change From Baseline in DAS28-CRP and DAS28-ESR in Period 2

The DAS assessment is a derived measurement with differential weight given to each component. The DAS28-ESR and DAS28-CRP was calculated at every visit within the clinical database in period 2. The components of the DAS28 ESR score assessment are: Tender/ Painful Joint Count (28), Swollen Joint Count (28); ESR, Subject General Health VAS assessment. The components of the DAS28 CRP score assessment were: Tender/Painful Joint Count (28); Swollen Joint Count (28), hsCRP, and the Subject General Health VAS assessment. This efficacy measurement was made at every study visit.

Time frame: Baseline, Weeks 24, 28, 36, 44 and 52

Arm	Measure	Group	Value (MEAN)	Dispersion
Etanercept	Change From Baseline in DAS28-CRP and DAS28-ESR in Period 2	DAS28-ESR Week 24 (N= 163, 168)	-3.79 units on a scale	Standard Deviation 1.04
Etanercept	Change From Baseline in DAS28-CRP and DAS28-ESR in Period 2	DAS28-CRP Week 24 (N= 163, 168)	-3.36 units on a scale	Standard Deviation 1.03
Etanercept	Change From Baseline in DAS28-CRP and DAS28-ESR in Period 2	DAS28-ESR Week 28 (N= 163, 168)	-3.35 units on a scale	Standard Deviation 1.31
Etanercept	Change From Baseline in DAS28-CRP and DAS28-ESR in Period 2	DAS28-CRP Week 28 (N= 160, 166)	-3.06 units on a scale	Standard Deviation 1.26
Etanercept	Change From Baseline in DAS28-CRP and DAS28-ESR in Period 2	DAS28-ESR Week 36 (N= 163, 168)	-3.20 units on a scale	Standard Deviation 1.4
Etanercept	Change From Baseline in DAS28-CRP and DAS28-ESR in Period 2	DAS28-CRP Week 36 (N= 162, 167)	-2.97 units on a scale	Standard Deviation 1.35
Etanercept	Change From Baseline in DAS28-CRP and DAS28-ESR in Period 2	DAS28-ESR Week 44 (N= 163, 168)	-3.15 units on a scale	Standard Deviation 1.36
Etanercept	Change From Baseline in DAS28-CRP and DAS28-ESR in Period 2	DAS28-CRP Week 44 (N= 162, 167)	-2.95 units on a scale	Standard Deviation 1.35
Etanercept	Change From Baseline in DAS28-CRP and DAS28-ESR in Period 2	DAS28-ESR Week 52 (N= 163, 168)	-3.08 units on a scale	Standard Deviation 1.4
Etanercept	Change From Baseline in DAS28-CRP and DAS28-ESR in Period 2	DAS28-CRP Week 52 (N= 162, 167)	-2.92 units on a scale	Standard Deviation 1.36
Placebo	Change From Baseline in DAS28-CRP and DAS28-ESR in Period 2	DAS28-CRP Week 44 (N= 162, 167)	-2.19 units on a scale	Standard Deviation 1.5
Placebo	Change From Baseline in DAS28-CRP and DAS28-ESR in Period 2	DAS28-ESR Week 24 (N= 163, 168)	-3.70 units on a scale	Standard Deviation 0.99
Placebo	Change From Baseline in DAS28-CRP and DAS28-ESR in Period 2	DAS28-CRP Week 36 (N= 162, 167)	-2.27 units on a scale	Standard Deviation 1.48
Placebo	Change From Baseline in DAS28-CRP and DAS28-ESR in Period 2	DAS28-CRP Week 24 (N= 163, 168)	-3.32 units on a scale	Standard Deviation 1.05
Placebo	Change From Baseline in DAS28-CRP and DAS28-ESR in Period 2	DAS28-CRP Week 52 (N= 162, 167)	-2.16 units on a scale	Standard Deviation 1.45
Placebo	Change From Baseline in DAS28-CRP and DAS28-ESR in Period 2	DAS28-ESR Week 28 (N= 163, 168)	-2.73 units on a scale	Standard Deviation 1.43
Placebo	Change From Baseline in DAS28-CRP and DAS28-ESR in Period 2	DAS28-ESR Week 44 (N= 163, 168)	-2.31 units on a scale	Standard Deviation 1.49
Placebo	Change From Baseline in DAS28-CRP and DAS28-ESR in Period 2	DAS28-CRP Week 28 (N= 160, 166)	-2.53 units on a scale	Standard Deviation 1.4
Placebo	Change From Baseline in DAS28-CRP and DAS28-ESR in Period 2	DAS28-ESR Week 52 (N= 163, 168)	-2.28 units on a scale	Standard Deviation 1.46
Placebo	Change From Baseline in DAS28-CRP and DAS28-ESR in Period 2	DAS28-ESR Week 36 (N= 163, 168)	-2.40 units on a scale	Standard Deviation 1.49

Comparison: DAS28-ESR Week 28p-value: <0.00195% CI: [-0.73, -0.2]ANCOVA

Comparison: DAS28-CRP Week 28p-value: 0.00695% CI: [-0.61, -0.11]ANCOVA

Comparison: DAS28-ESR Week 36p-value: <0.00195% CI: [-0.96, -0.39]ANCOVA

Comparison: DAS28-CRP Week 36p-value: <0.00195% CI: [-0.82, -0.28]ANCOVA

Comparison: DAS28-ESR Week 44p-value: <0.00195% CI: [-1.03, -0.46]ANCOVA

Comparison: DAS28-CRP Week 44p-value: <0.00195% CI: [-0.92, -0.37]ANCOVA

Comparison: DAS28-ESR Week 52p-value: <0.00195% CI: [-0.98, -0.4]ANCOVA

Comparison: DAS28-CRP Week 52p-value: <0.00195% CI: [-0.91, -0.36]ANCOVA

Secondary

Change in CRP and ESR at Each Visit During Period 1

Time frame: Baseline, Weeks 4, 8, 16 and 24

Population: The FAS for Period 1 (Open Label FAS) included all randomized participants who had at least one dose of open label study drug during Period 1 (ie, ETN or MTX).

Arm	Measure	Group	Value (MEAN)	Dispersion
Etanercept	Change in CRP and ESR at Each Visit During Period 1	CRP: Week 4 (N= 465)	-14.07 units on a scale	Standard Deviation 25.3
Etanercept	Change in CRP and ESR at Each Visit During Period 1	CRP: Week 8 (N= 471)	-14.43 units on a scale	Standard Deviation 23.51
Etanercept	Change in CRP and ESR at Each Visit During Period 1	CRP: Week 16 (N= 472)	-14.71 units on a scale	Standard Deviation 27.32
Etanercept	Change in CRP and ESR at Each Visit During Period 1	CRP: Week 24 (N= 472)	-14.51 units on a scale	Standard Deviation 27.64
Etanercept	Change in CRP and ESR at Each Visit During Period 1	ESR: Week 4 (N= 473)	-17.32 units on a scale	Standard Deviation 19.44
Etanercept	Change in CRP and ESR at Each Visit During Period 1	ESR: Week 8 (N= 473)	-19.28 units on a scale	Standard Deviation 21.62
Etanercept	Change in CRP and ESR at Each Visit During Period 1	ESR: Week 16 (N= 473)	-21.10 units on a scale	Standard Deviation 24.2
Etanercept	Change in CRP and ESR at Each Visit During Period 1	ESR: Week 24 (N= 473)	-26.77 units on a scale	Standard Deviation 26.19

Secondary

Change in CRP and ESR at Each Visit During Period 2

Time frame: Baseline, Weeks 24, 28, 36, 44 and 52

Arm	Measure	Group	Value (MEAN)	Dispersion
Etanercept	Change in CRP and ESR at Each Visit During Period 2	CRP: Week 28 (N= 160, 166)	-15.94 units on a scale	Standard Deviation 28.52
Etanercept	Change in CRP and ESR at Each Visit During Period 2	CRP: Week 24 (N= 161, 168)	-16.92 units on a scale	Standard Deviation 28.64
Etanercept	Change in CRP and ESR at Each Visit During Period 2	CRP: Week 36 (N= 162, 167)	-15.56 units on a scale	Standard Deviation 31.36
Etanercept	Change in CRP and ESR at Each Visit During Period 2	CRP: Week 44 (N= 162, 167)	-16.47 units on a scale	Standard Deviation 30.09
Etanercept	Change in CRP and ESR at Each Visit During Period 2	CRP: Week 52 (N= 162, 167)	-16.29 units on a scale	Standard Deviation 30.74
Etanercept	Change in CRP and ESR at Each Visit During Period 2	ESR: Week 24 (N= 163, 168)	-31.52 units on a scale	Standard Deviation 22.55
Etanercept	Change in CRP and ESR at Each Visit During Period 2	ESR: Week 28 (N= 163, 168)	-26.96 units on a scale	Standard Deviation 23.04
Etanercept	Change in CRP and ESR at Each Visit During Period 2	ESR: Week 36 (N= 163, 168)	-26.10 units on a scale	Standard Deviation 24.17
Etanercept	Change in CRP and ESR at Each Visit During Period 2	ESR: Week 44 (N= 163, 168)	-24.39 units on a scale	Standard Deviation 22.99
Etanercept	Change in CRP and ESR at Each Visit During Period 2	ESR: Week 52 (N= 163, 168)	-23.56 units on a scale	Standard Deviation 21.88
Placebo	Change in CRP and ESR at Each Visit During Period 2	ESR: Week 36 (N= 163, 168)	-16.94 units on a scale	Standard Deviation 23.08
Placebo	Change in CRP and ESR at Each Visit During Period 2	ESR: Week 24 (N= 163, 168)	-31.02 units on a scale	Standard Deviation 24.24
Placebo	Change in CRP and ESR at Each Visit During Period 2	CRP: Week 24 (N= 161, 168)	-14.47 units on a scale	Standard Deviation 21.59
Placebo	Change in CRP and ESR at Each Visit During Period 2	CRP: Week 28 (N= 160, 166)	-8.59 units on a scale	Standard Deviation 25.46
Placebo	Change in CRP and ESR at Each Visit During Period 2	ESR: Week 52 (N= 163, 168)	-16.27 units on a scale	Standard Deviation 22.65
Placebo	Change in CRP and ESR at Each Visit During Period 2	CRP: Week 36 (N= 162, 167)	-7.45 units on a scale	Standard Deviation 25.55
Placebo	Change in CRP and ESR at Each Visit During Period 2	ESR: Week 28 (N= 163, 168)	-20.28 units on a scale	Standard Deviation 23.68
Placebo	Change in CRP and ESR at Each Visit During Period 2	CRP: Week 44 (N= 162, 167)	-6.72 units on a scale	Standard Deviation 26.32
Placebo	Change in CRP and ESR at Each Visit During Period 2	ESR: Week 44 (N= 163, 168)	-16.14 units on a scale	Standard Deviation 23.1
Placebo	Change in CRP and ESR at Each Visit During Period 2	CRP: Week 52 (N= 162, 167)	-7.07 units on a scale	Standard Deviation 26.76

Comparison: CRP: Week 28p-value: 0.01495% CI: [-9.39, -1.05]ANCOVA

Comparison: CRP: Week 36p-value: 0.01195% CI: [-11.09, -1.46]ANCOVA

Comparison: CRP: Week 44p-value: <0.00195% CI: [-12.06, -3.44]ANCOVA

Comparison: CRP: Week 52p-value: 0.00195% CI: [-11.48, -2.85]ANCOVA

Comparison: ESR: Week 28p-value: <0.00195% CI: [-9.23, -2.49]ANCOVA

Comparison: ESR: Week 36p-value: <0.00195% CI: [-12.33, -5.05]ANCOVA

Comparison: ESR: Week 44p-value: <0.00195% CI: [-11.38, -3.8]ANCOVA

Comparison: ESR: Week 52p-value: <0.00195% CI: [-10.03, -2.6]ANCOVA

Secondary

Change in Morning Stiffness (Measured in Minutes) at Each Visit During Period 1

Morning stiffness was defined as stiffness in and around the joints, lasting at least 1 hour before maximal improvement. Participants assessed their overall disease activity over the last 2 to 3 days using a scale between 0 (no disease activity) and 10 (extreme disease activity), which corresponded to the magnitude of their pain) and marked one number with an 'X'.

Time frame: Baseline, Weeks 4, 8, 16 and 24

Population: The FAS for Period 1 (Open Label FAS) included all randomized participants who had at least one dose of open label study drug during Period 1 (ie, ETN or MTX).

Arm	Measure	Group	Value (MEAN)	Dispersion
Etanercept	Change in Morning Stiffness (Measured in Minutes) at Each Visit During Period 1	Week 4 (N= 467)	-78.56 minutes	Standard Deviation 143.68
Etanercept	Change in Morning Stiffness (Measured in Minutes) at Each Visit During Period 1	Week 8 (N= 467)	-90.58 minutes	Standard Deviation 147.42
Etanercept	Change in Morning Stiffness (Measured in Minutes) at Each Visit During Period 1	Week 16 (N= 467)	-102.25 minutes	Standard Deviation 158.76
Etanercept	Change in Morning Stiffness (Measured in Minutes) at Each Visit During Period 1	Week 24 (N= 467)	-109.32 minutes	Standard Deviation 183.15

Secondary

Change in Morning Stiffness (Measured in Minutes) at Each Visit During Period 2

Time frame: Baseline, Weeks 24, 28, 36, 44 and 52

Arm	Measure	Group	Value (MEAN)	Dispersion
Etanercept	Change in Morning Stiffness (Measured in Minutes) at Each Visit During Period 2	Week 28 (N= 163, 166)	-134.42 minutes	Standard Deviation 224.7
Etanercept	Change in Morning Stiffness (Measured in Minutes) at Each Visit During Period 2	Week 44 (N= 163, 166)	-129.86 minutes	Standard Deviation 223.78
Etanercept	Change in Morning Stiffness (Measured in Minutes) at Each Visit During Period 2	Week 36 (N= 163, 166)	-132.05 minutes	Standard Deviation 224.86
Etanercept	Change in Morning Stiffness (Measured in Minutes) at Each Visit During Period 2	Week 52 (N= 163, 166)	-129.49 minutes	Standard Deviation 223.68
Etanercept	Change in Morning Stiffness (Measured in Minutes) at Each Visit During Period 2	Week 24 (N= 163, 166)	-118.30 minutes	Standard Deviation 171.15
Placebo	Change in Morning Stiffness (Measured in Minutes) at Each Visit During Period 2	Week 52 (N= 163, 166)	-100.31 minutes	Standard Deviation 153.62
Placebo	Change in Morning Stiffness (Measured in Minutes) at Each Visit During Period 2	Week 24 (N= 163, 166)	-121.93 minutes	Standard Deviation 186.17
Placebo	Change in Morning Stiffness (Measured in Minutes) at Each Visit During Period 2	Week 28 (N= 163, 166)	-109.57 minutes	Standard Deviation 163.79
Placebo	Change in Morning Stiffness (Measured in Minutes) at Each Visit During Period 2	Week 36 (N= 163, 166)	-104.40 minutes	Standard Deviation 164.13
Placebo	Change in Morning Stiffness (Measured in Minutes) at Each Visit During Period 2	Week 44 (N= 163, 166)	-103.14 minutes	Standard Deviation 162.65

Comparison: Week 28p-value: 0.03395% CI: [-27.07, -1.16]ANCOVA

Comparison: Week 36p-value: 0.01395% CI: [-30.39, -3.68]ANCOVA

Comparison: Week 44p-value: 0.01995% CI: [-30.35, -2.73]ANCOVA

Comparison: Week 52p-value: 0.00795% CI: [-33.78, -5.54]ANCOVA

Secondary

Change in the Physician Global Assessment of Arthritis at Each Visit During Period 1

The investigator estimated the subject's overall disease activity over the last 2 to 3 days (independent of the Subject Global Assessment of arthritis) using a scale between 0 (no disease activity) and 10 (extreme disease activity) and marking one number with an 'X'.

Time frame: Baseline, Weeks 4, 8, 16 and 24

Population: The FAS for Period 1 (Open Label FAS) included all randomized participants who had at least one dose of open label study drug during Period 1 (ie, ETN or MTX).

Arm	Measure	Group	Value (MEAN)	Dispersion
Etanercept	Change in the Physician Global Assessment of Arthritis at Each Visit During Period 1	Week 4 (N= 473)	-2.60 units on a scale	Standard Deviation 1.78
Etanercept	Change in the Physician Global Assessment of Arthritis at Each Visit During Period 1	Week 8 (N= 473)	-3.46 units on a scale	Standard Deviation 1.9
Etanercept	Change in the Physician Global Assessment of Arthritis at Each Visit During Period 1	Week 16 (N= 473)	-4.12 units on a scale	Standard Deviation 1.96
Etanercept	Change in the Physician Global Assessment of Arthritis at Each Visit During Period 1	Week 24 (N= 473)	-4.79 units on a scale	Standard Deviation 2.02

Secondary

Change in the Physician Global Assessment of Arthritis at Each Visit During Period 2

Time frame: Baseline, Weeks 24, 28, 36, 44 and 52

Arm	Measure	Group	Value (MEAN)	Dispersion
Etanercept	Change in the Physician Global Assessment of Arthritis at Each Visit During Period 2	Week 28	-4.93 units on a scale	Standard Deviation 1.78
Etanercept	Change in the Physician Global Assessment of Arthritis at Each Visit During Period 2	Week 44	-4.82 units on a scale	Standard Deviation 2.02
Etanercept	Change in the Physician Global Assessment of Arthritis at Each Visit During Period 2	Week 36	-4.83 units on a scale	Standard Deviation 1.86
Etanercept	Change in the Physician Global Assessment of Arthritis at Each Visit During Period 2	Week 52	-4.77 units on a scale	Standard Deviation 2.03
Etanercept	Change in the Physician Global Assessment of Arthritis at Each Visit During Period 2	Week 24	-5.28 units on a scale	Standard Deviation 1.56
Placebo	Change in the Physician Global Assessment of Arthritis at Each Visit During Period 2	Week 52	-3.74 units on a scale	Standard Deviation 2.43
Placebo	Change in the Physician Global Assessment of Arthritis at Each Visit During Period 2	Week 24	-5.26 units on a scale	Standard Deviation 1.78
Placebo	Change in the Physician Global Assessment of Arthritis at Each Visit During Period 2	Week 28	-4.23 units on a scale	Standard Deviation 2.43
Placebo	Change in the Physician Global Assessment of Arthritis at Each Visit During Period 2	Week 36	-3.89 units on a scale	Standard Deviation 2.48
Placebo	Change in the Physician Global Assessment of Arthritis at Each Visit During Period 2	Week 44	-3.79 units on a scale	Standard Deviation 2.53

Comparison: Week 28p-value: 0.00595% CI: [-0.9, -0.16]ANCOVA

Comparison: Week 36p-value: <0.00195% CI: [-1.18, -0.38]ANCOVA

Comparison: Week 44p-value: <0.00195% CI: [-1.35, -0.54]ANCOVA

Comparison: Week 52p-value: <0.00195% CI: [-1.33, -0.53]ANCOVA

Secondary

Change in the Subject General Health VAS and Pain VAS at Each Visit During Period 2

Participants were asked to answer the question In general how would you rate your health over the last 2-3 weeks? by marking a vertical line at the appropriate position through the 100 mm VAS. The length on the line was measured from the left (in mm). For Pain VAS, participants assessed the severity of their arthritis pain during the last 2 to 3 days using a 100 mm VAS by marking a vertical line at the appropriate position on the scale between 0 (no pain) and 100 (most severe pain), which corresponded to the magnitude of their pain.

Time frame: Baseline, Weeks 24, 28, 36, 44 and 52

Arm	Measure	Group	Value (MEAN)	Dispersion
Etanercept	Change in the Subject General Health VAS and Pain VAS at Each Visit During Period 2	General Health VAS: Week 24	-46.66 units on a scale	Standard Deviation 24.72
Etanercept	Change in the Subject General Health VAS and Pain VAS at Each Visit During Period 2	General Health VAS: Week 28	-41.31 units on a scale	Standard Deviation 27.01
Etanercept	Change in the Subject General Health VAS and Pain VAS at Each Visit During Period 2	General Health VAS: Week 36	-39.84 units on a scale	Standard Deviation 26.56
Etanercept	Change in the Subject General Health VAS and Pain VAS at Each Visit During Period 2	General Health VAS: Week 44	-39.82 units on a scale	Standard Deviation 27.61
Etanercept	Change in the Subject General Health VAS and Pain VAS at Each Visit During Period 2	General Health VAS: Week 52	-39.81 units on a scale	Standard Deviation 28.16
Etanercept	Change in the Subject General Health VAS and Pain VAS at Each Visit During Period 2	Pain VAS: Week 24	-46.61 units on a scale	Standard Deviation 24.33
Etanercept	Change in the Subject General Health VAS and Pain VAS at Each Visit During Period 2	Pain VAS: Week 28	-43.30 units on a scale	Standard Deviation 26.34
Etanercept	Change in the Subject General Health VAS and Pain VAS at Each Visit During Period 2	Pain VAS: Week 36	-41.42 units on a scale	Standard Deviation 27.01
Etanercept	Change in the Subject General Health VAS and Pain VAS at Each Visit During Period 2	Pain VAS: Week 44	-41.21 units on a scale	Standard Deviation 28.01
Etanercept	Change in the Subject General Health VAS and Pain VAS at Each Visit During Period 2	Pain VAS: Week 52	-40.95 units on a scale	Standard Deviation 28.61
Placebo	Change in the Subject General Health VAS and Pain VAS at Each Visit During Period 2	Pain VAS: Week 36	-34.00 units on a scale	Standard Deviation 30.3
Placebo	Change in the Subject General Health VAS and Pain VAS at Each Visit During Period 2	General Health VAS: Week 24	-47.53 units on a scale	Standard Deviation 20.21
Placebo	Change in the Subject General Health VAS and Pain VAS at Each Visit During Period 2	Pain VAS: Week 24	-49.69 units on a scale	Standard Deviation 20.64
Placebo	Change in the Subject General Health VAS and Pain VAS at Each Visit During Period 2	General Health VAS: Week 28	-34.95 units on a scale	Standard Deviation 28.95
Placebo	Change in the Subject General Health VAS and Pain VAS at Each Visit During Period 2	Pain VAS: Week 52	-32.91 units on a scale	Standard Deviation 29.26
Placebo	Change in the Subject General Health VAS and Pain VAS at Each Visit During Period 2	General Health VAS: Week 36	-30.74 units on a scale	Standard Deviation 29.79
Placebo	Change in the Subject General Health VAS and Pain VAS at Each Visit During Period 2	Pain VAS: Week 28	-38.17 units on a scale	Standard Deviation 29.24
Placebo	Change in the Subject General Health VAS and Pain VAS at Each Visit During Period 2	General Health VAS: Week 44	-30.10 units on a scale	Standard Deviation 29.88
Placebo	Change in the Subject General Health VAS and Pain VAS at Each Visit During Period 2	Pain VAS: Week 44	-33.07 units on a scale	Standard Deviation 29.46
Placebo	Change in the Subject General Health VAS and Pain VAS at Each Visit During Period 2	General Health VAS: Week 52	-29.67 units on a scale	Standard Deviation 29.21

Comparison: General Health VAS: Week 28p-value: 0.07895% CI: [-8.91, 0.48]ANCOVA

Comparison: General Health VAS: Week 36p-value: 0.00395% CI: [-12.49, -2.59]ANCOVA

Comparison: General Health VAS: Week 44p-value: 0.00195% CI: [-13.2, -3.18]ANCOVA

Comparison: General Health VAS: Week 52p-value: <0.00195% CI: [-13.64, -3.55]ANCOVA

Comparison: Pain VAS: Week 28p-value: 0.01795% CI: [-10.75, -1.06]ANCOVA

Comparison: Pain VAS: Week 36p-value: 0.00195% CI: [-13.85, -3.34]ANCOVA

Comparison: Pain VAS: Week 44p-value: <0.00195% CI: [-14.72, -4.26]ANCOVA

Comparison: Pain VAS: Week 52p-value: <0.00195% CI: [-14.6, -3.99]ANCOVA

Secondary

Change in the Subject General Health Visual Analog Scale (VAS) and Pain VAS at Each Visit During Period 1

Participants were asked to answer the question In general how would you rate your health over the last 2 3 weeks? by marking a vertical line at the appropriate position through the 100 mm VAS. The length on the line was measured from the left (in mm). For Pain VAS, participants assessed the severity of their arthritis pain during the last 2 to 3 days using a 100 mm VAS by marking a vertical line at the appropriate position on the scale between 0 (no pain) and 100 (most severe pain), which corresponded to the magnitude of their pain.

Time frame: Baseline, Weeks 4, 8, 16 and 24

Population: The FAS for Period 1 (Open Label FAS) included all randomized participants who had at least one dose of open label study drug during Period 1 (ie, ETN or MTX).

Arm	Measure	Group	Value (MEAN)	Dispersion
Etanercept	Change in the Subject General Health Visual Analog Scale (VAS) and Pain VAS at Each Visit During Period 1	General Health VAS: Week 4 (N= 473)	-20.20 units on a scale	Standard Deviation 22.22
Etanercept	Change in the Subject General Health Visual Analog Scale (VAS) and Pain VAS at Each Visit During Period 1	General Health VAS: Week 8 (N= 473)	-25.17 units on a scale	Standard Deviation 24.59
Etanercept	Change in the Subject General Health Visual Analog Scale (VAS) and Pain VAS at Each Visit During Period 1	General Health VAS: Week 16 (N= 473)	-32.54 units on a scale	Standard Deviation 24.89
Etanercept	Change in the Subject General Health Visual Analog Scale (VAS) and Pain VAS at Each Visit During Period 1	General Health VAS: Week 24 (N= 473)	-40.67 units on a scale	Standard Deviation 26.28
Etanercept	Change in the Subject General Health Visual Analog Scale (VAS) and Pain VAS at Each Visit During Period 1	Pain VAS: Week 4 (N= 473)	-24.07 units on a scale	Standard Deviation 22.56
Etanercept	Change in the Subject General Health Visual Analog Scale (VAS) and Pain VAS at Each Visit During Period 1	Pain VAS: Week 8 (N= 473)	-28.55 units on a scale	Standard Deviation 24.08
Etanercept	Change in the Subject General Health Visual Analog Scale (VAS) and Pain VAS at Each Visit During Period 1	Pain VAS: Week 16 (N= 473)	-35.20 units on a scale	Standard Deviation 24.81
Etanercept	Change in the Subject General Health Visual Analog Scale (VAS) and Pain VAS at Each Visit During Period 1	Pain VAS: Week 24 (N= 473)	-42.49 units on a scale	Standard Deviation 26.05

Secondary

Change in the Subject Global Assessment of Arthritis in Period 1

Subjects assessed their overall disease activity over the last 2 to 3 days using a scale between 0 (no disease activity) and 10 (extreme disease activity), which corresponded to the magnitude of their pain) and marked one number with an 'X'.

Time frame: Baseline, Weeks 4, 8, 16 and 24

Population: The FAS for Period 1 (Open Label FAS) included all randomized participants who had at least one dose of open label study drug during Period 1 (ie, ETN or MTX).

Arm	Measure	Group	Value (MEAN)	Dispersion
Etanercept	Change in the Subject Global Assessment of Arthritis in Period 1	Week 4 (N= 473)	-2.18 units on a scale	Standard Deviation 2.21
Etanercept	Change in the Subject Global Assessment of Arthritis in Period 1	Week 8 (N= 473)	-2.60 units on a scale	Standard Deviation 2.34
Etanercept	Change in the Subject Global Assessment of Arthritis in Period 1	Week 16 (N= 473)	-3.32 units on a scale	Standard Deviation 2.44
Etanercept	Change in the Subject Global Assessment of Arthritis in Period 1	Week 24 (N= 473)	-3.97 units on a scale	Standard Deviation 2.6

Secondary

Change in the Subject Global Assessment of Arthritis in Period 2

Time frame: Baseline, Weeks 24, 28, 36, 44 and 52

Arm	Measure	Group	Value (MEAN)	Dispersion
Etanercept	Change in the Subject Global Assessment of Arthritis in Period 2	Week 36	-4.02 units on a scale	Standard Deviation 2.71
Etanercept	Change in the Subject Global Assessment of Arthritis in Period 2	Week 44	-3.92 units on a scale	Standard Deviation 2.79
Etanercept	Change in the Subject Global Assessment of Arthritis in Period 2	Week 28	-4.03 units on a scale	Standard Deviation 2.7
Etanercept	Change in the Subject Global Assessment of Arthritis in Period 2	Week 52	-3.91 units on a scale	Standard Deviation 2.84
Etanercept	Change in the Subject Global Assessment of Arthritis in Period 2	Week 24	-4.39 units on a scale	Standard Deviation 2.43
Placebo	Change in the Subject Global Assessment of Arthritis in Period 2	Week 52	-3.02 units on a scale	Standard Deviation 2.91
Placebo	Change in the Subject Global Assessment of Arthritis in Period 2	Week 24	-4.64 units on a scale	Standard Deviation 2.16
Placebo	Change in the Subject Global Assessment of Arthritis in Period 2	Week 28	-3.48 units on a scale	Standard Deviation 2.94
Placebo	Change in the Subject Global Assessment of Arthritis in Period 2	Week 44	-3.02 units on a scale	Standard Deviation 2.91
Placebo	Change in the Subject Global Assessment of Arthritis in Period 2	Week 36	-3.05 units on a scale	Standard Deviation 2.94

Comparison: Week 28p-value: 0.04895% CI: [-1, -0.01]ANCOVA

Comparison: Week 36p-value: <0.00195% CI: [-1.44, -0.43]ANCOVA

Comparison: Week 44p-value: 0.00195% CI: [-1.33, -0.33]ANCOVA

Comparison: Week 52p-value: 0.00295% CI: [-1.33, -0.31]ANCOVA

Secondary

Change in the Tender and Swollen Joint Counts at Each Visit During Period 1 (Using 28 Joint Count as Well as 66/68 Joint Counts).

A total of 66 swollen and 68 tender joints were assessed for tenderness/pain and swelling by the same qualified personnel (when possible) at each visit. For ACR responses, a 66/68 joint count was used. For DAS28-ESR, Simplified Disease Activity Index (SDAI), and Clinical Disease Activity Index (CDAI) calculations, the 28 joint count was used, which included: shoulders, elbows, wrists, metacarpophalangeal (MCP) joints, proximal interphalangeal (PIP) joints, and knees.

Time frame: Baseline, Weeks 4, 8, 16 and 24

Population: The FAS for Period 1 (Open Label FAS) included all randomized participants who had at least one dose of open label study drug during Period 1 (ie, ETN or MTX).

Arm	Measure	Group	Value (MEAN)	Dispersion
Etanercept	Change in the Tender and Swollen Joint Counts at Each Visit During Period 1 (Using 28 Joint Count as Well as 66/68 Joint Counts).	28 Tender Joint Count: Week 4	-6.49 Units on a scale	Standard Deviation 6.07
Etanercept	Change in the Tender and Swollen Joint Counts at Each Visit During Period 1 (Using 28 Joint Count as Well as 66/68 Joint Counts).	28 Tender Joint Count: Week 8	-8.59 Units on a scale	Standard Deviation 6.32
Etanercept	Change in the Tender and Swollen Joint Counts at Each Visit During Period 1 (Using 28 Joint Count as Well as 66/68 Joint Counts).	28 Tender Joint Count: Week 16	-10.12 Units on a scale	Standard Deviation 6.82
Etanercept	Change in the Tender and Swollen Joint Counts at Each Visit During Period 1 (Using 28 Joint Count as Well as 66/68 Joint Counts).	28 Tender Joint Count: Week 24	-11.50 Units on a scale	Standard Deviation 6.79
Etanercept	Change in the Tender and Swollen Joint Counts at Each Visit During Period 1 (Using 28 Joint Count as Well as 66/68 Joint Counts).	28 Swollen Joint Count: Week 4	-5.52 Units on a scale	Standard Deviation 5.02
Etanercept	Change in the Tender and Swollen Joint Counts at Each Visit During Period 1 (Using 28 Joint Count as Well as 66/68 Joint Counts).	28 Swollen Joint Count: Week 8	-7.04 Units on a scale	Standard Deviation 5.36
Etanercept	Change in the Tender and Swollen Joint Counts at Each Visit During Period 1 (Using 28 Joint Count as Well as 66/68 Joint Counts).	28 Swollen Joint Count: Week 16	-8.21 Units on a scale	Standard Deviation 5.44
Etanercept	Change in the Tender and Swollen Joint Counts at Each Visit During Period 1 (Using 28 Joint Count as Well as 66/68 Joint Counts).	28 Swollen Joint Count: Week 24	-9.01 Units on a scale	Standard Deviation 5.65
Etanercept	Change in the Tender and Swollen Joint Counts at Each Visit During Period 1 (Using 28 Joint Count as Well as 66/68 Joint Counts).	68 Tender Joint Count: Week 4	-9.71 Units on a scale	Standard Deviation 10
Etanercept	Change in the Tender and Swollen Joint Counts at Each Visit During Period 1 (Using 28 Joint Count as Well as 66/68 Joint Counts).	68 Tender Joint Count: Week 8	-13.02 Units on a scale	Standard Deviation 10.95
Etanercept	Change in the Tender and Swollen Joint Counts at Each Visit During Period 1 (Using 28 Joint Count as Well as 66/68 Joint Counts).	68 Tender Joint Count: Week 16	-15.21 Units on a scale	Standard Deviation 11.9
Etanercept	Change in the Tender and Swollen Joint Counts at Each Visit During Period 1 (Using 28 Joint Count as Well as 66/68 Joint Counts).	68 Tender Joint Count: Week 24	-17.41 Units on a scale	Standard Deviation 12.72
Etanercept	Change in the Tender and Swollen Joint Counts at Each Visit During Period 1 (Using 28 Joint Count as Well as 66/68 Joint Counts).	68 Swollen Joint Count: Week 4	-7.12 Units on a scale	Standard Deviation 6.86
Etanercept	Change in the Tender and Swollen Joint Counts at Each Visit During Period 1 (Using 28 Joint Count as Well as 66/68 Joint Counts).	68 Swollen Joint Count: Week 8	-9.03 Units on a scale	Standard Deviation 7.54
Etanercept	Change in the Tender and Swollen Joint Counts at Each Visit During Period 1 (Using 28 Joint Count as Well as 66/68 Joint Counts).	68 Swollen Joint Count: Week 16	-10.49 Units on a scale	Standard Deviation 7.62
Etanercept	Change in the Tender and Swollen Joint Counts at Each Visit During Period 1 (Using 28 Joint Count as Well as 66/68 Joint Counts).	68 Swollen Joint Count: Week 24	-11.53 Units on a scale	Standard Deviation 8.65

Secondary

Change in the Tender and Swollen Joint Counts at Each Visit During Period 2 (Using 28 Joint Count as Well as 66/68 Joint Counts).

Time frame: Baseline, Weeks 24, 28, 36, 44 and 52

Arm	Measure	Group	Value (MEAN)	Dispersion
Etanercept	Change in the Tender and Swollen Joint Counts at Each Visit During Period 2 (Using 28 Joint Count as Well as 66/68 Joint Counts).	28 Tender Joint Count: Week 24	-12.65 units on a scale	Standard Deviation 6.25
Etanercept	Change in the Tender and Swollen Joint Counts at Each Visit During Period 2 (Using 28 Joint Count as Well as 66/68 Joint Counts).	28 Tender Joint Count: Week 28	-11.69 units on a scale	Standard Deviation 6.74
Etanercept	Change in the Tender and Swollen Joint Counts at Each Visit During Period 2 (Using 28 Joint Count as Well as 66/68 Joint Counts).	28 Tender Joint Count: Week 36	-11.22 units on a scale	Standard Deviation 6.91
Etanercept	Change in the Tender and Swollen Joint Counts at Each Visit During Period 2 (Using 28 Joint Count as Well as 66/68 Joint Counts).	28 Tender Joint Count: Week 44	-11.19 units on a scale	Standard Deviation 6.82
Etanercept	Change in the Tender and Swollen Joint Counts at Each Visit During Period 2 (Using 28 Joint Count as Well as 66/68 Joint Counts).	28 Tender Joint Count: Week 52	-11.03 units on a scale	Standard Deviation 6.81
Etanercept	Change in the Tender and Swollen Joint Counts at Each Visit During Period 2 (Using 28 Joint Count as Well as 66/68 Joint Counts).	28 Swollen Joint Count: Week 24	-9.78 units on a scale	Standard Deviation 5.16
Etanercept	Change in the Tender and Swollen Joint Counts at Each Visit During Period 2 (Using 28 Joint Count as Well as 66/68 Joint Counts).	28 Swollen Joint Count: Week 28	-8.97 units on a scale	Standard Deviation 5.27
Etanercept	Change in the Tender and Swollen Joint Counts at Each Visit During Period 2 (Using 28 Joint Count as Well as 66/68 Joint Counts).	28 Swollen Joint Count: Week 36	-8.64 units on a scale	Standard Deviation 5.51
Etanercept	Change in the Tender and Swollen Joint Counts at Each Visit During Period 2 (Using 28 Joint Count as Well as 66/68 Joint Counts).	28 Swollen Joint Count: Week 44	-8.71 units on a scale	Standard Deviation 5.52
Etanercept	Change in the Tender and Swollen Joint Counts at Each Visit During Period 2 (Using 28 Joint Count as Well as 66/68 Joint Counts).	28 Swollen Joint Count: Week 52	-8.59 units on a scale	Standard Deviation 5.42
Etanercept	Change in the Tender and Swollen Joint Counts at Each Visit During Period 2 (Using 28 Joint Count as Well as 66/68 Joint Counts).	68 Tender Joint Count: Week 24	-18.31 units on a scale	Standard Deviation 12.13
Etanercept	Change in the Tender and Swollen Joint Counts at Each Visit During Period 2 (Using 28 Joint Count as Well as 66/68 Joint Counts).	68 Tender Joint Count: Week 28	-17.02 units on a scale	Standard Deviation 12.48
Etanercept	Change in the Tender and Swollen Joint Counts at Each Visit During Period 2 (Using 28 Joint Count as Well as 66/68 Joint Counts).	68 Tender Joint Count: Week 36	-17.27 units on a scale	Standard Deviation 12.55
Etanercept	Change in the Tender and Swollen Joint Counts at Each Visit During Period 2 (Using 28 Joint Count as Well as 66/68 Joint Counts).	68 Tender Joint Count: Week 44	-18.67 units on a scale	Standard Deviation 12.9
Etanercept	Change in the Tender and Swollen Joint Counts at Each Visit During Period 2 (Using 28 Joint Count as Well as 66/68 Joint Counts).	68 Tender Joint Count: Week 52	-17.88 units on a scale	Standard Deviation 13.21
Etanercept	Change in the Tender and Swollen Joint Counts at Each Visit During Period 2 (Using 28 Joint Count as Well as 66/68 Joint Counts).	68 Swollen Joint Count: Week 24	-12.09 units on a scale	Standard Deviation 7.76
Etanercept	Change in the Tender and Swollen Joint Counts at Each Visit During Period 2 (Using 28 Joint Count as Well as 66/68 Joint Counts).	68 Swollen Joint Count: Week 28	-11.23 units on a scale	Standard Deviation 7.77
Etanercept	Change in the Tender and Swollen Joint Counts at Each Visit During Period 2 (Using 28 Joint Count as Well as 66/68 Joint Counts).	68 Swollen Joint Count: Week 36	-11.26 units on a scale	Standard Deviation 8.05
Etanercept	Change in the Tender and Swollen Joint Counts at Each Visit During Period 2 (Using 28 Joint Count as Well as 66/68 Joint Counts).	68 Swollen Joint Count: Week 44	-12.00 units on a scale	Standard Deviation 8.03
Etanercept	Change in the Tender and Swollen Joint Counts at Each Visit During Period 2 (Using 28 Joint Count as Well as 66/68 Joint Counts).	68 Swollen Joint Count: Week 52	-11.98 units on a scale	Standard Deviation 8.17
Placebo	Change in the Tender and Swollen Joint Counts at Each Visit During Period 2 (Using 28 Joint Count as Well as 66/68 Joint Counts).	68 Swollen Joint Count: Week 36	-10.67 units on a scale	Standard Deviation 8.59
Placebo	Change in the Tender and Swollen Joint Counts at Each Visit During Period 2 (Using 28 Joint Count as Well as 66/68 Joint Counts).	28 Tender Joint Count: Week 24	-12.35 units on a scale	Standard Deviation 6.45
Placebo	Change in the Tender and Swollen Joint Counts at Each Visit During Period 2 (Using 28 Joint Count as Well as 66/68 Joint Counts).	68 Tender Joint Count: Week 24	-18.19 units on a scale	Standard Deviation 12.03
Placebo	Change in the Tender and Swollen Joint Counts at Each Visit During Period 2 (Using 28 Joint Count as Well as 66/68 Joint Counts).	28 Tender Joint Count: Week 28	-10.08 units on a scale	Standard Deviation 7.84
Placebo	Change in the Tender and Swollen Joint Counts at Each Visit During Period 2 (Using 28 Joint Count as Well as 66/68 Joint Counts).	68 Swollen Joint Count: Week 24	-12.40 units on a scale	Standard Deviation 8.45
Placebo	Change in the Tender and Swollen Joint Counts at Each Visit During Period 2 (Using 28 Joint Count as Well as 66/68 Joint Counts).	28 Tender Joint Count: Week 36	-9.23 units on a scale	Standard Deviation 8.07
Placebo	Change in the Tender and Swollen Joint Counts at Each Visit During Period 2 (Using 28 Joint Count as Well as 66/68 Joint Counts).	68 Tender Joint Count: Week 28	-15.20 units on a scale	Standard Deviation 13.95
Placebo	Change in the Tender and Swollen Joint Counts at Each Visit During Period 2 (Using 28 Joint Count as Well as 66/68 Joint Counts).	28 Tender Joint Count: Week 44	-8.97 units on a scale	Standard Deviation 8.01
Placebo	Change in the Tender and Swollen Joint Counts at Each Visit During Period 2 (Using 28 Joint Count as Well as 66/68 Joint Counts).	68 Swollen Joint Count: Week 52	-11.89 units on a scale	Standard Deviation 8.91
Placebo	Change in the Tender and Swollen Joint Counts at Each Visit During Period 2 (Using 28 Joint Count as Well as 66/68 Joint Counts).	28 Tender Joint Count: Week 52	-8.78 units on a scale	Standard Deviation 7.83
Placebo	Change in the Tender and Swollen Joint Counts at Each Visit During Period 2 (Using 28 Joint Count as Well as 66/68 Joint Counts).	68 Tender Joint Count: Week 36	-17.13 units on a scale	Standard Deviation 14.28
Placebo	Change in the Tender and Swollen Joint Counts at Each Visit During Period 2 (Using 28 Joint Count as Well as 66/68 Joint Counts).	28 Swollen Joint Count: Week 24	-9.98 units on a scale	Standard Deviation 5.58
Placebo	Change in the Tender and Swollen Joint Counts at Each Visit During Period 2 (Using 28 Joint Count as Well as 66/68 Joint Counts).	68 Swollen Joint Count: Week 28	-10.81 units on a scale	Standard Deviation 8.66
Placebo	Change in the Tender and Swollen Joint Counts at Each Visit During Period 2 (Using 28 Joint Count as Well as 66/68 Joint Counts).	28 Swollen Joint Count: Week 28	-8.70 units on a scale	Standard Deviation 5.94
Placebo	Change in the Tender and Swollen Joint Counts at Each Visit During Period 2 (Using 28 Joint Count as Well as 66/68 Joint Counts).	68 Tender Joint Count: Week 44	-18.82 units on a scale	Standard Deviation 14.71
Placebo	Change in the Tender and Swollen Joint Counts at Each Visit During Period 2 (Using 28 Joint Count as Well as 66/68 Joint Counts).	28 Swollen Joint Count: Week 36	-8.16 units on a scale	Standard Deviation 6.04
Placebo	Change in the Tender and Swollen Joint Counts at Each Visit During Period 2 (Using 28 Joint Count as Well as 66/68 Joint Counts).	68 Swollen Joint Count: Week 44	-11.63 units on a scale	Standard Deviation 8.58
Placebo	Change in the Tender and Swollen Joint Counts at Each Visit During Period 2 (Using 28 Joint Count as Well as 66/68 Joint Counts).	28 Swollen Joint Count: Week 44	-8.03 units on a scale	Standard Deviation 6.08
Placebo	Change in the Tender and Swollen Joint Counts at Each Visit During Period 2 (Using 28 Joint Count as Well as 66/68 Joint Counts).	68 Tender Joint Count: Week 52	-17.61 units on a scale	Standard Deviation 12.57
Placebo	Change in the Tender and Swollen Joint Counts at Each Visit During Period 2 (Using 28 Joint Count as Well as 66/68 Joint Counts).	28 Swollen Joint Count: Week 52	-7.98 units on a scale	Standard Deviation 6.05

Comparison: 28 Tender Joint Count: Week 28p-value: 0.06295% CI: [-1.84, 0.05]ANCOVA

Comparison: 28 Tender Joint Count: Week 36p-value: 0.01595% CI: [-2.41, -0.27]ANCOVA

Comparison: 28 Tender Joint Count: Week 44p-value: 0.00395% CI: [-2.72, -0.57]ANCOVA

Comparison: 28 Tender Joint Count: Week 52p-value: 0.00295% CI: [-2.85, -0.66]ANCOVA

Comparison: 28 Swollen Joint Count: Week 28p-value: 0.6895% CI: [-0.77, 0.5]ANCOVA

Comparison: 28 Swollen Joint Count: Week 36p-value: 0.43795% CI: [-1.04, 0.45]ANCOVA

Comparison: 28 Swollen Joint Count: Week 44p-value: 0.13195% CI: [-1.31, 0.17]ANCOVA

Comparison: 28 Swollen Joint Count: Week 52p-value: 0.19995% CI: [-1.22, 0.25]ANCOVA

Comparison: 68 Tender Joint Count: Week 28p-value: 0.11595% CI: [-2.6, 0.28]ANCOVA

Comparison: 68 Tender Joint Count: Week 36p-value: 0.01795% CI: [-3.42, -0.35]ANCOVA

Comparison: 68 Tender Joint Count: Week 44p-value: 0.00495% CI: [-3.91, -0.76]ANCOVA

Comparison: 68 Tender Joint Count: Week 52p-value: 0.00295% CI: [-4.19, -0.97]ANCOVA

Comparison: 68 Swollen Joint Count: Week 28p-value: 0.36895% CI: [-1.13, 0.42]ANCOVA

Comparison: 68 Swollen Joint Count: Week 36p-value: 0.20895% CI: [-1.46, 0.32]ANCOVA

Comparison: 68 Swollen Joint Count: Week 44p-value: 0.06495% CI: [-1.73, 0.05]ANCOVA

Comparison: 68 Swollen Joint Count: Week 52p-value: 0.08195% CI: [-1.66, 0.1]ANCOVA

Secondary

Change of CDAI and SDAI at Each Visit During Period 1.

SDAI and CDAI are defined as: 1\) SDAI = DAS28 prorated Swollen Joint Count (0-28) + DAS28 prorated Tender Joint Count (0-28) + Physician Global Assessment of arthritis (0-10) + Subject Global Assessment of arthritis (0-10) + hs CRP (in mg/dL) in Period 1. 2) CDAI = DAS28 prorated Swollen Joint Count (0-28) + DAS28 prorated Tender Joint Count (0 28) + Physician Global Assessment of arthritis (0-10) + Subject Global Assessment of arthritis (0-10) in Period 1.

Time frame: Baseline, Weeks 4, 8, 16 and 24

Population: The FAS for Period 1 (Open Label FAS) included all randomized participants who had at least one dose of open label study drug during Period 1 (ie, ETN or MTX).

Arm	Measure	Group	Value (MEAN)	Dispersion
Etanercept	Change of CDAI and SDAI at Each Visit During Period 1.	CDAI Week 4 (N= 473)	-16.78 units on a scale	Standard Deviation 11.72
Etanercept	Change of CDAI and SDAI at Each Visit During Period 1.	CDAI Week 8 (N= 473)	-21.69 units on a scale	Standard Deviation 12.4
Etanercept	Change of CDAI and SDAI at Each Visit During Period 1.	CDAI Week 16 (N= 473)	-25.77 units on a scale	Standard Deviation 13.19
Etanercept	Change of CDAI and SDAI at Each Visit During Period 1.	CDAI Week 24 (N= 473)	-29.25 units on a scale	Standard Deviation 13.66
Etanercept	Change of CDAI and SDAI at Each Visit During Period 1.	SDAI Week 4 (N= 465)	-18.19 units on a scale	Standard Deviation 12.44
Etanercept	Change of CDAI and SDAI at Each Visit During Period 1.	SDAI Week 8 (N= 471)	-23.06 units on a scale	Standard Deviation 12.89
Etanercept	Change of CDAI and SDAI at Each Visit During Period 1.	SDAI Week 16 (N= 472)	-27.17 units on a scale	Standard Deviation 13.61
Etanercept	Change of CDAI and SDAI at Each Visit During Period 1.	SDAI Week 24 (N= 472)	-30.56 units on a scale	Standard Deviation 14.27

Secondary

Change of CDAI and SDAI at Each Visit During Period 2

SDAI and CDAI are defined as: 1\) SDAI = DAS28 prorated Swollen Joint Count (0-28) + DAS28 prorated Tender Joint Count (0-28) + Physician Global Assessment of arthritis (0-10) + Subject Global Assessment of arthritis (0-10) + hs CRP (in mg/dL) in Period 2. 2) CDAI = DAS28 prorated Swollen Joint Count (0-28) + DAS28 prorated Tender Joint Count (0 28) + Physician Global Assessment of arthritis (0-10) + Subject Global Assessment of arthritis (0-10) in Period 2.

Time frame: Baseline, Weeks 24, 28, 36, 44 and 52

Arm	Measure	Group	Value (MEAN)	Dispersion
Etanercept	Change of CDAI and SDAI at Each Visit During Period 2	CDAI: Week 24 (N= 163, 168)	-32.11 units on a scale	Standard Deviation 12.06
Etanercept	Change of CDAI and SDAI at Each Visit During Period 2	CDAI: Week 28 (N= 163, 168)	-29.62 units on a scale	Standard Deviation 13.1
Etanercept	Change of CDAI and SDAI at Each Visit During Period 2	CDAI: Week 36 (N= 163, 168)	-28.71 units on a scale	Standard Deviation 13.56
Etanercept	Change of CDAI and SDAI at Each Visit During Period 2	CDAI: Week 44 (N= 163, 168)	-28.63 units on a scale	Standard Deviation 13.58
Etanercept	Change of CDAI and SDAI at Each Visit During Period 2	CDAI: Week 52 (N= 163, 168)	-28.30 units on a scale	Standard Deviation 13.61
Etanercept	Change of CDAI and SDAI at Each Visit During Period 2	SDAI: Week 24 (N= 163, 168)	-33.61 units on a scale	Standard Deviation 12.07
Etanercept	Change of CDAI and SDAI at Each Visit During Period 2	SDAI: Week 28 (N= 160, 166)	-31.07 units on a scale	Standard Deviation 13.58
Etanercept	Change of CDAI and SDAI at Each Visit During Period 2	SDAI: Week 36 (N= 162, 167)	-30.20 units on a scale	Standard Deviation 14.05
Etanercept	Change of CDAI and SDAI at Each Visit During Period 2	SDAI: Week 44 (N= 162, 167)	-30.21 units on a scale	Standard Deviation 14.14
Etanercept	Change of CDAI and SDAI at Each Visit During Period 2	SDAI: Week 52 (N= 162, 167)	-29.86 units on a scale	Standard Deviation 14.03
Placebo	Change of CDAI and SDAI at Each Visit During Period 2	SDAI: Week 36 (N= 162, 167)	-25.44 units on a scale	Standard Deviation 17.17
Placebo	Change of CDAI and SDAI at Each Visit During Period 2	CDAI: Week 24 (N= 163, 168)	-32.23 units on a scale	Standard Deviation 12.49
Placebo	Change of CDAI and SDAI at Each Visit During Period 2	SDAI: Week 24 (N= 163, 168)	-33.68 units on a scale	Standard Deviation 13.03
Placebo	Change of CDAI and SDAI at Each Visit During Period 2	CDAI: Week 28 (N= 163, 168)	-26.49 units on a scale	Standard Deviation 15.87
Placebo	Change of CDAI and SDAI at Each Visit During Period 2	SDAI: Week 52 (N= 162, 167)	-24.57 units on a scale	Standard Deviation 16.79
Placebo	Change of CDAI and SDAI at Each Visit During Period 2	CDAI: Week 36 (N= 163, 168)	-24.33 units on a scale	Standard Deviation 16.45
Placebo	Change of CDAI and SDAI at Each Visit During Period 2	SDAI: Week 28 (N= 160, 166)	-27.58 units on a scale	Standard Deviation 16.5
Placebo	Change of CDAI and SDAI at Each Visit During Period 2	CDAI: Week 44 (N= 163, 168)	-23.81 units on a scale	Standard Deviation 16.48
Placebo	Change of CDAI and SDAI at Each Visit During Period 2	SDAI: Week 44 (N= 162, 167)	-24.85 units on a scale	Standard Deviation 17.29
Placebo	Change of CDAI and SDAI at Each Visit During Period 2	CDAI: Week 52 (N= 163, 168)	-23.52 units on a scale	Standard Deviation 15.98

Comparison: CDAI: Week 28p-value: 0.04995% CI: [-4.19, -0.01]ANCOVA

Comparison: CDAI: Week 36p-value: 0.00595% CI: [-5.72, -1.05]ANCOVA

Comparison: CDAI: Week 44p-value: <0.00195% CI: [-6.37, -1.67]ANCOVA

Comparison: CDAI: Week 52p-value: <0.00195% CI: [-6.36, -1.68]ANCOVA

Comparison: SDAI: Week 28p-value: 0.04795% CI: [-4.4, -0.03]ANCOVA

Comparison: SDAI: Week 36p-value: 0.00495% CI: [-5.97, -1.12]ANCOVA

Comparison: SDAI: Week 44p-value: <0.00195% CI: [-6.78, -1.88]ANCOVA

Comparison: SDAI: Week 52p-value: <0.00195% CI: [-6.7, -1.84]ANCOVA

Secondary

Percentage of Participants Achieving ACR20, ACR50, ACR70 and ACR90 (by 66/68 Joint Counts) During Period 2 at Each Visit.

A 66 swollen and 68 tender joint count was used for calculating ACR responses. The ACR's definition for calculating improvement in RA (ACR20) was calculated as a 20% improvement in tender and swollen joint counts and 20% improvement in 3 of the 5 remaining ACR core set measures: subject and physician global assessments of arthritis, pain, disability, and an acute phase reactant. Similarly, ACR50, ACR70 and ACR90 were calculated with the respective percent improvement. This efficacy measurement was made at every study visit.

Time frame: Baseline, Weeks 24, 28, 36, 44 and 52

Arm	Measure	Group	Value (NUMBER)
Etanercept	Percentage of Participants Achieving ACR20, ACR50, ACR70 and ACR90 (by 66/68 Joint Counts) During Period 2 at Each Visit.	ACR 20: Week 24 (N= 161, 168)	96.3 Percentage of participants
Etanercept	Percentage of Participants Achieving ACR20, ACR50, ACR70 and ACR90 (by 66/68 Joint Counts) During Period 2 at Each Visit.	ACR 20: Week 28 (N= 161, 168)	91.3 Percentage of participants
Etanercept	Percentage of Participants Achieving ACR20, ACR50, ACR70 and ACR90 (by 66/68 Joint Counts) During Period 2 at Each Visit.	ACR 20: Week 36 (N= 161, 168)	88.2 Percentage of participants
Etanercept	Percentage of Participants Achieving ACR20, ACR50, ACR70 and ACR90 (by 66/68 Joint Counts) During Period 2 at Each Visit.	ACR 20: Week 44 (N= 161, 168)	86.3 Percentage of participants
Etanercept	Percentage of Participants Achieving ACR20, ACR50, ACR70 and ACR90 (by 66/68 Joint Counts) During Period 2 at Each Visit.	ACR 20: Week 52 (N= 161, 168)	87.0 Percentage of participants
Etanercept	Percentage of Participants Achieving ACR20, ACR50, ACR70 and ACR90 (by 66/68 Joint Counts) During Period 2 at Each Visit.	ACR 50: Week 24 (N= 161, 168)	88.2 Percentage of participants
Etanercept	Percentage of Participants Achieving ACR20, ACR50, ACR70 and ACR90 (by 66/68 Joint Counts) During Period 2 at Each Visit.	ACR 50: Week 28 (N= 161, 168)	75.2 Percentage of participants
Etanercept	Percentage of Participants Achieving ACR20, ACR50, ACR70 and ACR90 (by 66/68 Joint Counts) During Period 2 at Each Visit.	ACR 50: Week 36 (N= 161, 168)	68.9 Percentage of participants
Etanercept	Percentage of Participants Achieving ACR20, ACR50, ACR70 and ACR90 (by 66/68 Joint Counts) During Period 2 at Each Visit.	ACR 50: Week 44 (N= 161, 168)	69.6 Percentage of participants
Etanercept	Percentage of Participants Achieving ACR20, ACR50, ACR70 and ACR90 (by 66/68 Joint Counts) During Period 2 at Each Visit.	ACR 50: Week 52 (N= 161, 168)	68.3 Percentage of participants
Etanercept	Percentage of Participants Achieving ACR20, ACR50, ACR70 and ACR90 (by 66/68 Joint Counts) During Period 2 at Each Visit.	ACR 70: Week 24 (N= 161, 168)	49.7 Percentage of participants
Etanercept	Percentage of Participants Achieving ACR20, ACR50, ACR70 and ACR90 (by 66/68 Joint Counts) During Period 2 at Each Visit.	ACR 70: Week 28 (N= 161, 168)	41.0 Percentage of participants
Etanercept	Percentage of Participants Achieving ACR20, ACR50, ACR70 and ACR90 (by 66/68 Joint Counts) During Period 2 at Each Visit.	ACR 70: Week 36 (N= 161, 168)	44.7 Percentage of participants
Etanercept	Percentage of Participants Achieving ACR20, ACR50, ACR70 and ACR90 (by 66/68 Joint Counts) During Period 2 at Each Visit.	ACR 70: Week 44 (N= 161, 168)	43.5 Percentage of participants
Etanercept	Percentage of Participants Achieving ACR20, ACR50, ACR70 and ACR90 (by 66/68 Joint Counts) During Period 2 at Each Visit.	ACR 70: Week 52 (N= 161, 168)	41.0 Percentage of participants
Etanercept	Percentage of Participants Achieving ACR20, ACR50, ACR70 and ACR90 (by 66/68 Joint Counts) During Period 2 at Each Visit.	ACR 90: Week 24 (N= 161, 168)	8.1 Percentage of participants
Etanercept	Percentage of Participants Achieving ACR20, ACR50, ACR70 and ACR90 (by 66/68 Joint Counts) During Period 2 at Each Visit.	ACR 90: Week 28 (N= 161, 168)	8.7 Percentage of participants
Etanercept	Percentage of Participants Achieving ACR20, ACR50, ACR70 and ACR90 (by 66/68 Joint Counts) During Period 2 at Each Visit.	ACR 90: Week 36 (N= 161, 168)	11.8 Percentage of participants
Etanercept	Percentage of Participants Achieving ACR20, ACR50, ACR70 and ACR90 (by 66/68 Joint Counts) During Period 2 at Each Visit.	ACR 90: Week 44 (N= 161, 168)	9.3 Percentage of participants
Etanercept	Percentage of Participants Achieving ACR20, ACR50, ACR70 and ACR90 (by 66/68 Joint Counts) During Period 2 at Each Visit.	ACR 90: Week 52 (N= 161, 168)	13.0 Percentage of participants
Placebo	Percentage of Participants Achieving ACR20, ACR50, ACR70 and ACR90 (by 66/68 Joint Counts) During Period 2 at Each Visit.	ACR 90: Week 36 (N= 161, 168)	5.4 Percentage of participants
Placebo	Percentage of Participants Achieving ACR20, ACR50, ACR70 and ACR90 (by 66/68 Joint Counts) During Period 2 at Each Visit.	ACR 20: Week 24 (N= 161, 168)	96.4 Percentage of participants
Placebo	Percentage of Participants Achieving ACR20, ACR50, ACR70 and ACR90 (by 66/68 Joint Counts) During Period 2 at Each Visit.	ACR 70: Week 24 (N= 161, 168)	52.4 Percentage of participants
Placebo	Percentage of Participants Achieving ACR20, ACR50, ACR70 and ACR90 (by 66/68 Joint Counts) During Period 2 at Each Visit.	ACR 20: Week 28 (N= 161, 168)	81.5 Percentage of participants
Placebo	Percentage of Participants Achieving ACR20, ACR50, ACR70 and ACR90 (by 66/68 Joint Counts) During Period 2 at Each Visit.	ACR 90: Week 24 (N= 161, 168)	8.3 Percentage of participants
Placebo	Percentage of Participants Achieving ACR20, ACR50, ACR70 and ACR90 (by 66/68 Joint Counts) During Period 2 at Each Visit.	ACR 20: Week 36 (N= 161, 168)	76.8 Percentage of participants
Placebo	Percentage of Participants Achieving ACR20, ACR50, ACR70 and ACR90 (by 66/68 Joint Counts) During Period 2 at Each Visit.	ACR 70: Week 28 (N= 161, 168)	33.9 Percentage of participants
Placebo	Percentage of Participants Achieving ACR20, ACR50, ACR70 and ACR90 (by 66/68 Joint Counts) During Period 2 at Each Visit.	ACR 20: Week 44 (N= 161, 168)	76.2 Percentage of participants
Placebo	Percentage of Participants Achieving ACR20, ACR50, ACR70 and ACR90 (by 66/68 Joint Counts) During Period 2 at Each Visit.	ACR 90: Week 52 (N= 161, 168)	7.1 Percentage of participants
Placebo	Percentage of Participants Achieving ACR20, ACR50, ACR70 and ACR90 (by 66/68 Joint Counts) During Period 2 at Each Visit.	ACR 20: Week 52 (N= 161, 168)	76.2 Percentage of participants
Placebo	Percentage of Participants Achieving ACR20, ACR50, ACR70 and ACR90 (by 66/68 Joint Counts) During Period 2 at Each Visit.	ACR 70: Week 36 (N= 161, 168)	27.4 Percentage of participants
Placebo	Percentage of Participants Achieving ACR20, ACR50, ACR70 and ACR90 (by 66/68 Joint Counts) During Period 2 at Each Visit.	ACR 50: Week 24 (N= 161, 168)	85.7 Percentage of participants
Placebo	Percentage of Participants Achieving ACR20, ACR50, ACR70 and ACR90 (by 66/68 Joint Counts) During Period 2 at Each Visit.	ACR 90: Week 28 (N= 161, 168)	5.4 Percentage of participants
Placebo	Percentage of Participants Achieving ACR20, ACR50, ACR70 and ACR90 (by 66/68 Joint Counts) During Period 2 at Each Visit.	ACR 50: Week 28 (N= 161, 168)	63.7 Percentage of participants
Placebo	Percentage of Participants Achieving ACR20, ACR50, ACR70 and ACR90 (by 66/68 Joint Counts) During Period 2 at Each Visit.	ACR 70: Week 44 (N= 161, 168)	25.0 Percentage of participants
Placebo	Percentage of Participants Achieving ACR20, ACR50, ACR70 and ACR90 (by 66/68 Joint Counts) During Period 2 at Each Visit.	ACR 50: Week 36 (N= 161, 168)	51.8 Percentage of participants
Placebo	Percentage of Participants Achieving ACR20, ACR50, ACR70 and ACR90 (by 66/68 Joint Counts) During Period 2 at Each Visit.	ACR 90: Week 44 (N= 161, 168)	4.8 Percentage of participants
Placebo	Percentage of Participants Achieving ACR20, ACR50, ACR70 and ACR90 (by 66/68 Joint Counts) During Period 2 at Each Visit.	ACR 50: Week 44 (N= 161, 168)	50.6 Percentage of participants
Placebo	Percentage of Participants Achieving ACR20, ACR50, ACR70 and ACR90 (by 66/68 Joint Counts) During Period 2 at Each Visit.	ACR 70: Week 52 (N= 161, 168)	25.0 Percentage of participants
Placebo	Percentage of Participants Achieving ACR20, ACR50, ACR70 and ACR90 (by 66/68 Joint Counts) During Period 2 at Each Visit.	ACR 50: Week 52 (N= 161, 168)	50.6 Percentage of participants

Comparison: ACR 20: Week 24p-value: 0.74295% CI: [-4.21, 3.9]Cochran-Mantel-Haenszel

Comparison: ACR 20: Week 28p-value: 0.14395% CI: [2.45, 17.06]Cochran-Mantel-Haenszel

Comparison: ACR 20: Week 36p-value: 0.11195% CI: [3.31, 19.51]Cochran-Mantel-Haenszel

Comparison: ACR 20: Week 44p-value: 0.17595% CI: [1.8, 18.49]Cochran-Mantel-Haenszel

Comparison: ACR 20: Week 52p-value: 0.08895% CI: [2.49, 19.05]Cochran-Mantel-Haenszel

Comparison: ACR 50: Week 24p-value: 0.58495% CI: [-4.78, 9.75]Cochran-Mantel-Haenszel

Comparison: ACR 50: Week 28p-value: 0.22695% CI: [1.59, 21.34]Cochran-Mantel-Haenszel

Comparison: ACR 50: Week 36p-value: 0.01295% CI: [6.76, 27.56]Cochran-Mantel-Haenszel

Comparison: ACR 50: Week 44p-value: 0.00695% CI: [8.59, 29.35]Cochran-Mantel-Haenszel

Comparison: ACR 50: Week 52p-value: 0.01495% CI: [7.3, 28.16]Cochran-Mantel-Haenszel

Comparison: ACR 70: Week 24p-value: 0.70295% CI: [-13.49, 8.11]Cochran-Mantel-Haenszel

Comparison: ACR 70: Week 28p-value: 0.37895% CI: [-3.37, 17.5]Cochran-Mantel-Haenszel

Comparison: ACR 70: Week 36p-value: 0.00495% CI: [7.12, 27.56]Cochran-Mantel-Haenszel

Comparison: ACR 70: Week 44p-value: 0.00195% CI: [8.4, 28.55]Cochran-Mantel-Haenszel

Comparison: ACR 70: Week 52p-value: 0.00595% CI: [5.96, 26.02]Cochran-Mantel-Haenszel

Comparison: ACR 90: Week 24p-value: 0.92195% CI: [-6.19, 5.67]Cochran-Mantel-Haenszel

Comparison: ACR 90: Week 28p-value: 0.4195% CI: [-2.19, 8.86]Cochran-Mantel-Haenszel

Comparison: ACR 90: Week 36p-value: 0.07395% CI: [0.41, 12.48]Cochran-Mantel-Haenszel

Comparison: ACR 90: Week 44p-value: 0.21995% CI: [-0.97, 10.08]Cochran-Mantel-Haenszel

Comparison: ACR 90: Week 52p-value: 0.19695% CI: [-0.6, 12.4]Cochran-Mantel-Haenszel

Secondary

Percentage of Participants Achieving American College of Rheumatology (ACR) ACR20, ACR50, ACR70 and ACR90 (by 66/68 Joint Counts) During Period 1 at Each Visit.

Time frame: Baseline, Weeks 4, 8, 16 and 24

Population: The FAS for Period 1 (Open Label FAS) included all randomized participants who had at least one dose of open label study drug during Period 1 (ie, ETN or MTX).

Arm	Measure	Group	Value (NUMBER)	Dispersion
Etanercept	Percentage of Participants Achieving American College of Rheumatology (ACR) ACR20, ACR50, ACR70 and ACR90 (by 66/68 Joint Counts) During Period 1 at Each Visit.	ACR 20: Week 4 (N= 469)	58.6 percentage of participants	1.08
Etanercept	Percentage of Participants Achieving American College of Rheumatology (ACR) ACR20, ACR50, ACR70 and ACR90 (by 66/68 Joint Counts) During Period 1 at Each Visit.	ACR 20: Week 8 (N= 469)	73.1 percentage of participants	1.05
Etanercept	Percentage of Participants Achieving American College of Rheumatology (ACR) ACR20, ACR50, ACR70 and ACR90 (by 66/68 Joint Counts) During Period 1 at Each Visit.	ACR 20: Week 16 (N= 469)	83.6 percentage of participants	1.18
Etanercept	Percentage of Participants Achieving American College of Rheumatology (ACR) ACR20, ACR50, ACR70 and ACR90 (by 66/68 Joint Counts) During Period 1 at Each Visit.	ACR 20: Week 24 (N= 469)	87.8 percentage of participants	1.14
Etanercept	Percentage of Participants Achieving American College of Rheumatology (ACR) ACR20, ACR50, ACR70 and ACR90 (by 66/68 Joint Counts) During Period 1 at Each Visit.	ACR 50: Week 4 (N= 469)	19.8 percentage of participants	1.26
Etanercept	Percentage of Participants Achieving American College of Rheumatology (ACR) ACR20, ACR50, ACR70 and ACR90 (by 66/68 Joint Counts) During Period 1 at Each Visit.	ACR 50: Week 8 (N= 469)	35.8 percentage of participants	1.21
Etanercept	Percentage of Participants Achieving American College of Rheumatology (ACR) ACR20, ACR50, ACR70 and ACR90 (by 66/68 Joint Counts) During Period 1 at Each Visit.	ACR 50: Week 16 (N= 469)	55.2 percentage of participants	1.35
Etanercept	Percentage of Participants Achieving American College of Rheumatology (ACR) ACR20, ACR50, ACR70 and ACR90 (by 66/68 Joint Counts) During Period 1 at Each Visit.	ACR 50: Week 24 (N= 469)	72.5 percentage of participants	1.27
Etanercept	Percentage of Participants Achieving American College of Rheumatology (ACR) ACR20, ACR50, ACR70 and ACR90 (by 66/68 Joint Counts) During Period 1 at Each Visit.	ACR 70: Week 4 (N= 469)	4.3 percentage of participants	—
Etanercept	Percentage of Participants Achieving American College of Rheumatology (ACR) ACR20, ACR50, ACR70 and ACR90 (by 66/68 Joint Counts) During Period 1 at Each Visit.	ACR 70: Week 8 (N= 469)	11.1 percentage of participants	—
Etanercept	Percentage of Participants Achieving American College of Rheumatology (ACR) ACR20, ACR50, ACR70 and ACR90 (by 66/68 Joint Counts) During Period 1 at Each Visit.	ACR 70: Week 16 (N= 469)	23.7 percentage of participants	—
Etanercept	Percentage of Participants Achieving American College of Rheumatology (ACR) ACR20, ACR50, ACR70 and ACR90 (by 66/68 Joint Counts) During Period 1 at Each Visit.	ACR 70: Week 24 (N= 469)	39.4 percentage of participants	—
Etanercept	Percentage of Participants Achieving American College of Rheumatology (ACR) ACR20, ACR50, ACR70 and ACR90 (by 66/68 Joint Counts) During Period 1 at Each Visit.	ACR 90: Week 4 (N= 469)	0.0 percentage of participants	—
Etanercept	Percentage of Participants Achieving American College of Rheumatology (ACR) ACR20, ACR50, ACR70 and ACR90 (by 66/68 Joint Counts) During Period 1 at Each Visit.	ACR 90: Week 8 (N= 469)	0.4 percentage of participants	—
Etanercept	Percentage of Participants Achieving American College of Rheumatology (ACR) ACR20, ACR50, ACR70 and ACR90 (by 66/68 Joint Counts) During Period 1 at Each Visit.	ACR 90: Week 16 (N= 469)	1.5 percentage of participants	—
Etanercept	Percentage of Participants Achieving American College of Rheumatology (ACR) ACR20, ACR50, ACR70 and ACR90 (by 66/68 Joint Counts) During Period 1 at Each Visit.	ACR 90: Week 24 (N= 469)	5.8 percentage of participants	—

Secondary

Percentage of Participants Achieving EULAR Good and or Moderate Responses (by Both DAS28-ESR and DAS28-CRP Scores) at Each Visit During Period 2.

EULAR response is based on DAS28-ESR scores. The following good and moderate response is defined based on DAS28-ESR at endpoint (DAS28-ESR improvement at from Baseline in parenthesis): ≤3.2 units (\>1.2 units) is good response; ≤3.2 units (0.6-1.2 units) are moderate response; ≤3.2 units (≤0.6 units) are no response.

Time frame: Baseline, Weeks 24, 28, 36, 44 and 52

Arm	Measure	Group	Value (NUMBER)
Etanercept	Percentage of Participants Achieving EULAR Good and or Moderate Responses (by Both DAS28-ESR and DAS28-CRP Scores) at Each Visit During Period 2.	Good Response: DAS28-ESR Week 28 (N= 163, 168)	62.6 Percentage of participants
Etanercept	Percentage of Participants Achieving EULAR Good and or Moderate Responses (by Both DAS28-ESR and DAS28-CRP Scores) at Each Visit During Period 2.	Moderate Response: DAS28-ESR Week 24 (N= 163, 168)	100.0 Percentage of participants
Etanercept	Percentage of Participants Achieving EULAR Good and or Moderate Responses (by Both DAS28-ESR and DAS28-CRP Scores) at Each Visit During Period 2.	Good Response: DAS28-CRP Week 36 (N= 162, 167)	67.9 Percentage of participants
Etanercept	Percentage of Participants Achieving EULAR Good and or Moderate Responses (by Both DAS28-ESR and DAS28-CRP Scores) at Each Visit During Period 2.	Moderate Response: DAS28-CRP Week 24 (N= 163, 168)	100.0 Percentage of participants
Etanercept	Percentage of Participants Achieving EULAR Good and or Moderate Responses (by Both DAS28-ESR and DAS28-CRP Scores) at Each Visit During Period 2.	Good Response: DAS28-CRP Week 24 (N= 163, 168)	86.5 Percentage of participants
Etanercept	Percentage of Participants Achieving EULAR Good and or Moderate Responses (by Both DAS28-ESR and DAS28-CRP Scores) at Each Visit During Period 2.	Moderate Response: DAS28-ESR Week 28 (N= 163, 168)	95.7 Percentage of participants
Etanercept	Percentage of Participants Achieving EULAR Good and or Moderate Responses (by Both DAS28-ESR and DAS28-CRP Scores) at Each Visit During Period 2.	Good Response: DAS28-ESR Week 44 (N= 163, 168)	50.9 Percentage of participants
Etanercept	Percentage of Participants Achieving EULAR Good and or Moderate Responses (by Both DAS28-ESR and DAS28-CRP Scores) at Each Visit During Period 2.	Moderate Response: DAS28-CRP Week 28 (N= 160, 166)	96.9 Percentage of participants
Etanercept	Percentage of Participants Achieving EULAR Good and or Moderate Responses (by Both DAS28-ESR and DAS28-CRP Scores) at Each Visit During Period 2.	Good Response: DAS28-CRP Week 28 (N= 160, 166)	73.1 Percentage of participants
Etanercept	Percentage of Participants Achieving EULAR Good and or Moderate Responses (by Both DAS28-ESR and DAS28-CRP Scores) at Each Visit During Period 2.	Moderate Response: DAS28-ESR Week 36 (N= 163, 168)	93.9 Percentage of participants
Etanercept	Percentage of Participants Achieving EULAR Good and or Moderate Responses (by Both DAS28-ESR and DAS28-CRP Scores) at Each Visit During Period 2.	Good Response: DAS28-CRP Week 44 (N= 162, 167)	68.5 Percentage of participants
Etanercept	Percentage of Participants Achieving EULAR Good and or Moderate Responses (by Both DAS28-ESR and DAS28-CRP Scores) at Each Visit During Period 2.	Moderate Response: DAS28-CRP Week 36 (N= 162, 167)	94.4 Percentage of participants
Etanercept	Percentage of Participants Achieving EULAR Good and or Moderate Responses (by Both DAS28-ESR and DAS28-CRP Scores) at Each Visit During Period 2.	Good Response: DAS28-ESR Week 24 (N= 163, 168)	99.4 Percentage of participants
Etanercept	Percentage of Participants Achieving EULAR Good and or Moderate Responses (by Both DAS28-ESR and DAS28-CRP Scores) at Each Visit During Period 2.	Moderate Response: DAS28-ESR Week 44 (N= 163, 168)	93.3 Percentage of participants
Etanercept	Percentage of Participants Achieving EULAR Good and or Moderate Responses (by Both DAS28-ESR and DAS28-CRP Scores) at Each Visit During Period 2.	Good Response: DAS28-ESR Week 52 (N= 163, 168)	42.9 Percentage of participants
Etanercept	Percentage of Participants Achieving EULAR Good and or Moderate Responses (by Both DAS28-ESR and DAS28-CRP Scores) at Each Visit During Period 2.	Moderate Response: DAS28-CRP Week 44 (N= 162, 167)	95.1 Percentage of participants
Etanercept	Percentage of Participants Achieving EULAR Good and or Moderate Responses (by Both DAS28-ESR and DAS28-CRP Scores) at Each Visit During Period 2.	Good Response: DAS28-ESR Week 36 (N= 163, 168)	55.2 Percentage of participants
Etanercept	Percentage of Participants Achieving EULAR Good and or Moderate Responses (by Both DAS28-ESR and DAS28-CRP Scores) at Each Visit During Period 2.	Moderate Response: DAS28-ESR Week 52 (N= 163, 168)	93.3 Percentage of participants
Etanercept	Percentage of Participants Achieving EULAR Good and or Moderate Responses (by Both DAS28-ESR and DAS28-CRP Scores) at Each Visit During Period 2.	Moderate Response: DAS28-CRP Week 52 (N= 162, 167)	95.7 Percentage of participants
Etanercept	Percentage of Participants Achieving EULAR Good and or Moderate Responses (by Both DAS28-ESR and DAS28-CRP Scores) at Each Visit During Period 2.	Good Response: DAS28-CRP Week 52 (N= 162, 167)	63.0 Percentage of participants
Placebo	Percentage of Participants Achieving EULAR Good and or Moderate Responses (by Both DAS28-ESR and DAS28-CRP Scores) at Each Visit During Period 2.	Moderate Response: DAS28-CRP Week 52 (N= 162, 167)	84.4 Percentage of participants
Placebo	Percentage of Participants Achieving EULAR Good and or Moderate Responses (by Both DAS28-ESR and DAS28-CRP Scores) at Each Visit During Period 2.	Good Response: DAS28-ESR Week 24 (N= 163, 168)	99.4 Percentage of participants
Placebo	Percentage of Participants Achieving EULAR Good and or Moderate Responses (by Both DAS28-ESR and DAS28-CRP Scores) at Each Visit During Period 2.	Good Response: DAS28-CRP Week 24 (N= 163, 168)	85.1 Percentage of participants
Placebo	Percentage of Participants Achieving EULAR Good and or Moderate Responses (by Both DAS28-ESR and DAS28-CRP Scores) at Each Visit During Period 2.	Good Response: DAS28-ESR Week 28 (N= 163, 168)	41.1 Percentage of participants
Placebo	Percentage of Participants Achieving EULAR Good and or Moderate Responses (by Both DAS28-ESR and DAS28-CRP Scores) at Each Visit During Period 2.	Good Response: DAS28-CRP Week 28 (N= 160, 166)	54.8 Percentage of participants
Placebo	Percentage of Participants Achieving EULAR Good and or Moderate Responses (by Both DAS28-ESR and DAS28-CRP Scores) at Each Visit During Period 2.	Good Response: DAS28-ESR Week 36 (N= 163, 168)	23.8 Percentage of participants
Placebo	Percentage of Participants Achieving EULAR Good and or Moderate Responses (by Both DAS28-ESR and DAS28-CRP Scores) at Each Visit During Period 2.	Good Response: DAS28-CRP Week 36 (N= 162, 167)	40.7 Percentage of participants
Placebo	Percentage of Participants Achieving EULAR Good and or Moderate Responses (by Both DAS28-ESR and DAS28-CRP Scores) at Each Visit During Period 2.	Good Response: DAS28-ESR Week 44 (N= 163, 168)	19.6 Percentage of participants
Placebo	Percentage of Participants Achieving EULAR Good and or Moderate Responses (by Both DAS28-ESR and DAS28-CRP Scores) at Each Visit During Period 2.	Good Response: DAS28-CRP Week 44 (N= 162, 167)	37.7 Percentage of participants
Placebo	Percentage of Participants Achieving EULAR Good and or Moderate Responses (by Both DAS28-ESR and DAS28-CRP Scores) at Each Visit During Period 2.	Good Response: DAS28-ESR Week 52 (N= 163, 168)	16.7 Percentage of participants
Placebo	Percentage of Participants Achieving EULAR Good and or Moderate Responses (by Both DAS28-ESR and DAS28-CRP Scores) at Each Visit During Period 2.	Good Response: DAS28-CRP Week 52 (N= 162, 167)	35.9 Percentage of participants
Placebo	Percentage of Participants Achieving EULAR Good and or Moderate Responses (by Both DAS28-ESR and DAS28-CRP Scores) at Each Visit During Period 2.	Moderate Response: DAS28-ESR Week 24 (N= 163, 168)	100.0 Percentage of participants
Placebo	Percentage of Participants Achieving EULAR Good and or Moderate Responses (by Both DAS28-ESR and DAS28-CRP Scores) at Each Visit During Period 2.	Moderate Response: DAS28-CRP Week 24 (N= 163, 168)	100.0 Percentage of participants
Placebo	Percentage of Participants Achieving EULAR Good and or Moderate Responses (by Both DAS28-ESR and DAS28-CRP Scores) at Each Visit During Period 2.	Moderate Response: DAS28-ESR Week 28 (N= 163, 168)	87.5 Percentage of participants
Placebo	Percentage of Participants Achieving EULAR Good and or Moderate Responses (by Both DAS28-ESR and DAS28-CRP Scores) at Each Visit During Period 2.	Moderate Response: DAS28-CRP Week 28 (N= 160, 166)	90.4 Percentage of participants
Placebo	Percentage of Participants Achieving EULAR Good and or Moderate Responses (by Both DAS28-ESR and DAS28-CRP Scores) at Each Visit During Period 2.	Moderate Response: DAS28-ESR Week 36 (N= 163, 168)	83.9 Percentage of participants
Placebo	Percentage of Participants Achieving EULAR Good and or Moderate Responses (by Both DAS28-ESR and DAS28-CRP Scores) at Each Visit During Period 2.	Moderate Response: DAS28-CRP Week 36 (N= 162, 167)	85.6 Percentage of participants
Placebo	Percentage of Participants Achieving EULAR Good and or Moderate Responses (by Both DAS28-ESR and DAS28-CRP Scores) at Each Visit During Period 2.	Moderate Response: DAS28-ESR Week 44 (N= 163, 168)	81.5 Percentage of participants
Placebo	Percentage of Participants Achieving EULAR Good and or Moderate Responses (by Both DAS28-ESR and DAS28-CRP Scores) at Each Visit During Period 2.	Moderate Response: DAS28-CRP Week 44 (N= 162, 167)	84.4 Percentage of participants
Placebo	Percentage of Participants Achieving EULAR Good and or Moderate Responses (by Both DAS28-ESR and DAS28-CRP Scores) at Each Visit During Period 2.	Moderate Response: DAS28-ESR Week 52 (N= 163, 168)	82.1 Percentage of participants

Comparison: Good Response: DAS28-CRP Week 24p-value: 0.96195% CI: [-6.13, 8.9]Cochran-Mantel-Haenszel

Comparison: Good Response: DAS28-ESR Week 28p-value: 0.00195% CI: [10.99, 32.02]Cochran-Mantel-Haenszel

Comparison: Good Response: DAS28-CRP Week 28p-value: 0.00795% CI: [8.08, 28.53]Cochran-Mantel-Haenszel

Comparison: Good Response: DAS28-ESR Week 36p-value: <0.00195% CI: [21.42, 41.39]Cochran-Mantel-Haenszel

Comparison: Good Response: DAS28-CRP Week 36p-value: <0.00195% CI: [16.83, 37.54]Cochran-Mantel-Haenszel

Comparison: Good Response: DAS28-ESR Week 44p-value: <0.00195% CI: [21.53, 41.02]Cochran-Mantel-Haenszel

Comparison: Good Response: DAS28-CRP Week 44p-value: <0.00195% CI: [20.54, 41.05]Cochran-Mantel-Haenszel

Comparison: Good Response: DAS28-ESR Week 52p-value: <0.00195% CI: [16.82, 35.74]Cochran-Mantel-Haenszel

Comparison: Good Response: DAS28-CRP Week 52p-value: <0.00195% CI: [16.63, 37.44]Cochran-Mantel-Haenszel

Comparison: Good Response: DAS28-ESR Week 24p-value: 0.76695% CI: [-1.69, 1.65]Cochran-Mantel-Haenszel

Comparison: Moderate Response: DAS28-ESR Week 28p-value: 0.09195% CI: [2.32, 14.1]Cochran-Mantel-Haenszel

Comparison: Moderate Response: DAS28-CRP Week 28p-value: 0.22795% CI: [1.28, 11.75]Cochran-Mantel-Haenszel

Comparison: Moderate Response: DAS28-ESR Week 36p-value: 0.07295% CI: [3.27, 16.6]Cochran-Mantel-Haenszel

Comparison: Moderate Response: DAS28-CRP Week 36p-value: 0.10895% CI: [2.43, 15.2]Cochran-Mantel-Haenszel

Comparison: Moderate Response: DAS28-ESR Week 44p-value: 0.03595% CI: [4.69, 18.72]Cochran-Mantel-Haenszel

Comparison: Moderate Response: DAS28-ESR Week 44p-value: 0.0395% CI: [4.2, 17.06]Cochran-Mantel-Haenszel

Comparison: Moderate Response: DAS28-ESR Week 52p-value: 0.04895% CI: [4.15, 18.06]Cochran-Mantel-Haenszel

Comparison: Moderate Response: DAS28-CRP Week 52p-value: 0.01695% CI: [4.92, 17.58]Cochran-Mantel-Haenszel

Secondary

Percentage of Participants Achieving European League Against Rheumatism (EULAR) Good and or Moderate Responses (by Both DAS28-ESR and DAS28-CRP Scores) at Each Visit During Period 1.

Time frame: Baseline, Weeks 4, 8, 16 and 24

Population: The FAS for Period 1 (Open Label FAS) included all randomized participants who had at least one dose of open label study drug during Period 1 (ie, ETN or MTX).

Arm	Measure	Group	Value (NUMBER)
Etanercept	Percentage of Participants Achieving European League Against Rheumatism (EULAR) Good and or Moderate Responses (by Both DAS28-ESR and DAS28-CRP Scores) at Each Visit During Period 1.	Good Response: DAS28-ESR Week 4 (N= 473)	9.5 Percentage of participants
Etanercept	Percentage of Participants Achieving European League Against Rheumatism (EULAR) Good and or Moderate Responses (by Both DAS28-ESR and DAS28-CRP Scores) at Each Visit During Period 1.	Good Response: DAS28-CRP Week 4 (N= 465)	18.9 Percentage of participants
Etanercept	Percentage of Participants Achieving European League Against Rheumatism (EULAR) Good and or Moderate Responses (by Both DAS28-ESR and DAS28-CRP Scores) at Each Visit During Period 1.	Good Response: DAS28-ESR Week 8 (N= 473)	19.5 Percentage of participants
Etanercept	Percentage of Participants Achieving European League Against Rheumatism (EULAR) Good and or Moderate Responses (by Both DAS28-ESR and DAS28-CRP Scores) at Each Visit During Period 1.	Good Response: DAS28-CRP Week 8 (N= 471)	33.5 Percentage of participants
Etanercept	Percentage of Participants Achieving European League Against Rheumatism (EULAR) Good and or Moderate Responses (by Both DAS28-ESR and DAS28-CRP Scores) at Each Visit During Period 1.	Good Response: DAS28-ESR Week 16 (N= 473)	32.3 Percentage of participants
Etanercept	Percentage of Participants Achieving European League Against Rheumatism (EULAR) Good and or Moderate Responses (by Both DAS28-ESR and DAS28-CRP Scores) at Each Visit During Period 1.	Good Response: DAS28-CRP Week 16 (N= 472)	51.9 Percentage of participants
Etanercept	Percentage of Participants Achieving European League Against Rheumatism (EULAR) Good and or Moderate Responses (by Both DAS28-ESR and DAS28-CRP Scores) at Each Visit During Period 1.	Good Response: DAS28-ESR Week 24 (N= 473)	71.5 Percentage of participants
Etanercept	Percentage of Participants Achieving European League Against Rheumatism (EULAR) Good and or Moderate Responses (by Both DAS28-ESR and DAS28-CRP Scores) at Each Visit During Period 1.	Good Response: DAS28-CRP Week 24 (N= 472)	71.4 Percentage of participants
Etanercept	Percentage of Participants Achieving European League Against Rheumatism (EULAR) Good and or Moderate Responses (by Both DAS28-ESR and DAS28-CRP Scores) at Each Visit During Period 1.	Moderate Response: DAS28-ESR Week 4 (N= 473)	69.1 Percentage of participants
Etanercept	Percentage of Participants Achieving European League Against Rheumatism (EULAR) Good and or Moderate Responses (by Both DAS28-ESR and DAS28-CRP Scores) at Each Visit During Period 1.	Moderate Response: DAS28-CRP Week 4 (N= 465)	79.8 Percentage of participants
Etanercept	Percentage of Participants Achieving European League Against Rheumatism (EULAR) Good and or Moderate Responses (by Both DAS28-ESR and DAS28-CRP Scores) at Each Visit During Period 1.	Moderate Response: DAS28-ESR Week 8 (N= 473)	86.9 Percentage of participants
Etanercept	Percentage of Participants Achieving European League Against Rheumatism (EULAR) Good and or Moderate Responses (by Both DAS28-ESR and DAS28-CRP Scores) at Each Visit During Period 1.	Moderate Response: DAS28-CRP Week 8 (N= 471)	87.5 Percentage of participants
Etanercept	Percentage of Participants Achieving European League Against Rheumatism (EULAR) Good and or Moderate Responses (by Both DAS28-ESR and DAS28-CRP Scores) at Each Visit During Period 1.	Moderate Response: DAS28-ESR Week 16 (N= 473)	92.0 Percentage of participants
Etanercept	Percentage of Participants Achieving European League Against Rheumatism (EULAR) Good and or Moderate Responses (by Both DAS28-ESR and DAS28-CRP Scores) at Each Visit During Period 1.	Moderate Response: DAS28-CRP Week 16 (N= 472)	92.8 Percentage of participants
Etanercept	Percentage of Participants Achieving European League Against Rheumatism (EULAR) Good and or Moderate Responses (by Both DAS28-ESR and DAS28-CRP Scores) at Each Visit During Period 1.	Moderate Response: DAS28-ESR Week 24 (N= 473)	94.1 Percentage of participants
Etanercept	Percentage of Participants Achieving European League Against Rheumatism (EULAR) Good and or Moderate Responses (by Both DAS28-ESR and DAS28-CRP Scores) at Each Visit During Period 1.	Moderate Response: DAS28-CRP Week 24 (N= 472)	95.1 Percentage of participants

Secondary

Percentage of Participants Achieving LDA (DAS28-ESR and DAS28-C-reactive Protein [CRP]) at Each Visit During Period 1

Proportion of participants who achieved LDA (DAS28-ESR and DAS28-CRP at each visit during period 1 is presented below.

Time frame: Baseline, Weeks 4, 8, 16 and 24

Population: The FAS for Period 1 (Open Label FAS) included all randomized participants who had at least one dose of open label study drug during Period 1 (ie, ETN or MTX).

Arm	Measure	Group	Value (NUMBER)
Etanercept	Percentage of Participants Achieving LDA (DAS28-ESR and DAS28-C-reactive Protein [CRP]) at Each Visit During Period 1	DAS28-CRP Week 8 (N= 471)	34.6 Percentage of participants
Etanercept	Percentage of Participants Achieving LDA (DAS28-ESR and DAS28-C-reactive Protein [CRP]) at Each Visit During Period 1	DAS28-ESR Week 16 (N= 473)	32.8 Percentage of participants
Etanercept	Percentage of Participants Achieving LDA (DAS28-ESR and DAS28-C-reactive Protein [CRP]) at Each Visit During Period 1	DAS28-CRP Week 16 (N= 472)	52.8 Percentage of participants
Etanercept	Percentage of Participants Achieving LDA (DAS28-ESR and DAS28-C-reactive Protein [CRP]) at Each Visit During Period 1	DAS28-ESR Week 4 (N= 473)	9.5 Percentage of participants
Etanercept	Percentage of Participants Achieving LDA (DAS28-ESR and DAS28-C-reactive Protein [CRP]) at Each Visit During Period 1	DAS28-CRP Week 4 (N= 465)	20.6 Percentage of participants
Etanercept	Percentage of Participants Achieving LDA (DAS28-ESR and DAS28-C-reactive Protein [CRP]) at Each Visit During Period 1	DAS28-ESR Week 8 (N= 473)	20.3 Percentage of participants
Etanercept	Percentage of Participants Achieving LDA (DAS28-ESR and DAS28-C-reactive Protein [CRP]) at Each Visit During Period 1	DAS28-ESR Week 24 (N= 473)	72.1 Percentage of participants
Etanercept	Percentage of Participants Achieving LDA (DAS28-ESR and DAS28-C-reactive Protein [CRP]) at Each Visit During Period 1	DAS28-CRP Week 24 (N= 472)	72.5 Percentage of participants

Secondary

Percentage of Participants Achieving LDA (DAS28-ESR and DAS28-CRP) at Each Visit During Period 2

Proportion of participants who achieved LDA (DAS28-ESR and DAS28-CRP at each visit during period 2 is presented below.

Time frame: Baseline, Weeks 24, 28, 36, 44 and 52

Arm	Measure	Group	Value (NUMBER)
Etanercept	Percentage of Participants Achieving LDA (DAS28-ESR and DAS28-CRP) at Each Visit During Period 2	DAS28-ESR Baseline (N= 163, 168)	0.0 Percentage of participants
Etanercept	Percentage of Participants Achieving LDA (DAS28-ESR and DAS28-CRP) at Each Visit During Period 2	DAS28-CRP Baseline (N= 163, 168)	0.6 Percentage of participants
Etanercept	Percentage of Participants Achieving LDA (DAS28-ESR and DAS28-CRP) at Each Visit During Period 2	DAS28-ESR Week 24 (N= 163, 168)	100.0 Percentage of participants
Etanercept	Percentage of Participants Achieving LDA (DAS28-ESR and DAS28-CRP) at Each Visit During Period 2	DAS28-CRP Week 24 (N= 163, 168)	87.7 Percentage of participants
Etanercept	Percentage of Participants Achieving LDA (DAS28-ESR and DAS28-CRP) at Each Visit During Period 2	DAS28-ESR Week 28 (N= 163, 168)	62.6 Percentage of participants
Etanercept	Percentage of Participants Achieving LDA (DAS28-ESR and DAS28-CRP) at Each Visit During Period 2	DAS28-CRP Week 28 (N= 160, 166)	74.4 Percentage of participants
Etanercept	Percentage of Participants Achieving LDA (DAS28-ESR and DAS28-CRP) at Each Visit During Period 2	DAS28-ESR Week 36 (N= 163, 168)	55.2 Percentage of participants
Etanercept	Percentage of Participants Achieving LDA (DAS28-ESR and DAS28-CRP) at Each Visit During Period 2	DAS28-CRP Week 36 (N= 162, 167)	69.1 Percentage of participants
Etanercept	Percentage of Participants Achieving LDA (DAS28-ESR and DAS28-CRP) at Each Visit During Period 2	DAS28-ESR Week 44 (N= 163, 168)	51.5 Percentage of participants
Etanercept	Percentage of Participants Achieving LDA (DAS28-ESR and DAS28-CRP) at Each Visit During Period 2	DAS28-CRP Week 44 (N= 162, 167)	69.1 Percentage of participants
Etanercept	Percentage of Participants Achieving LDA (DAS28-ESR and DAS28-CRP) at Each Visit During Period 2	DAS28-ESR Week 52 (N= 163, 168)	43.6 Percentage of participants
Etanercept	Percentage of Participants Achieving LDA (DAS28-ESR and DAS28-CRP) at Each Visit During Period 2	DAS28-CRP Week 52 (N= 162, 167)	64.2 Percentage of participants
Placebo	Percentage of Participants Achieving LDA (DAS28-ESR and DAS28-CRP) at Each Visit During Period 2	DAS28-ESR Week 52 (N= 163, 168)	17.3 Percentage of participants
Placebo	Percentage of Participants Achieving LDA (DAS28-ESR and DAS28-CRP) at Each Visit During Period 2	DAS28-ESR Baseline (N= 163, 168)	0.6 Percentage of participants
Placebo	Percentage of Participants Achieving LDA (DAS28-ESR and DAS28-CRP) at Each Visit During Period 2	DAS28-ESR Week 36 (N= 163, 168)	24.4 Percentage of participants
Placebo	Percentage of Participants Achieving LDA (DAS28-ESR and DAS28-CRP) at Each Visit During Period 2	DAS28-CRP Baseline (N= 163, 168)	0.0 Percentage of participants
Placebo	Percentage of Participants Achieving LDA (DAS28-ESR and DAS28-CRP) at Each Visit During Period 2	DAS28-CRP Week 44 (N= 162, 167)	38.9 Percentage of participants
Placebo	Percentage of Participants Achieving LDA (DAS28-ESR and DAS28-CRP) at Each Visit During Period 2	DAS28-ESR Week 24 (N= 163, 168)	100.0 Percentage of participants
Placebo	Percentage of Participants Achieving LDA (DAS28-ESR and DAS28-CRP) at Each Visit During Period 2	DAS28-CRP Week 36 (N= 162, 167)	41.9 Percentage of participants
Placebo	Percentage of Participants Achieving LDA (DAS28-ESR and DAS28-CRP) at Each Visit During Period 2	DAS28-CRP Week 24 (N= 163, 168)	85.1 Percentage of participants
Placebo	Percentage of Participants Achieving LDA (DAS28-ESR and DAS28-CRP) at Each Visit During Period 2	DAS28-CRP Week 52 (N= 162, 167)	37.1 Percentage of participants
Placebo	Percentage of Participants Achieving LDA (DAS28-ESR and DAS28-CRP) at Each Visit During Period 2	DAS28-ESR Week 28 (N= 163, 168)	41.1 Percentage of participants
Placebo	Percentage of Participants Achieving LDA (DAS28-ESR and DAS28-CRP) at Each Visit During Period 2	DAS28-ESR Week 44 (N= 163, 168)	20.2 Percentage of participants
Placebo	Percentage of Participants Achieving LDA (DAS28-ESR and DAS28-CRP) at Each Visit During Period 2	DAS28-CRP Week 28 (N= 160, 166)	55.4 Percentage of participants

Comparison: DAS28-ESR Baselinep-value: 0.37195% CI: [-1.76, 0.57]Cochran-Mantel-Haenszel

Comparison: DAS28-CRP Baselinep-value: 0.35895% CI: [-0.59, 1.81]Cochran-Mantel-Haenszel

Comparison: DAS28-CRP Week 24p-value: 0.66795% CI: [-4.76, 9.98]Cochran-Mantel-Haenszel

Comparison: DAS28-ESR Week 28p-value: 0.00195% CI: [10.99, 32.02]Cochran-Mantel-Haenszel

Comparison: DAS28-CRP Week 28p-value: 0.00495% CI: [8.81, 29.1]Cochran-Mantel-Haenszel

Comparison: DAS28-ESR Week 36p-value: <0.00195% CI: [20.79, 40.83]Cochran-Mantel-Haenszel

Comparison: DAS28-CRP Week 36p-value: <0.00195% CI: [16.89, 37.54]Cochran-Mantel-Haenszel

Comparison: DAS28-ESR Week 44p-value: <0.00195% CI: [21.51, 41.08]Cochran-Mantel-Haenszel

Comparison: DAS28-CRP Week 44p-value: <0.00195% CI: [19.95, 40.47]Cochran-Mantel-Haenszel

Comparison: DAS28-ESR Week 52p-value: <0.00195% CI: [16.78, 35.81]Cochran-Mantel-Haenszel

Comparison: DAS28-CRP Week 52p-value: <0.00195% CI: [16.67, 37.47]Cochran-Mantel-Haenszel

Secondary

Percentage of Participants Achieving LDA or Remission Based on CDAI and SDAI at Each Visit During Period 2.

SDAI and CDAI are defined as: 1\) SDAI = DAS28 prorated Swollen Joint Count (0-28) + DAS28 prorated Tender Joint Count (0-28) + Physician Global Assessment of arthritis (0-10) + Subject Global Assessment of arthritis (0-10) + hs CRP (in mg/dL) in Period 2. 2) CDAI = DAS28 prorated Swollen Joint Count (0-28) + DAS28 prorated Tender Joint Count (0 28) + Physician Global Assessment of arthritis (0-10) + Subject Global Assessment of arthritis (0-10) in Period 2.

Time frame: Baseline, Weeks 24, 28, 36, 44 and 52

Arm	Measure	Group	Value (NUMBER)
Etanercept	Percentage of Participants Achieving LDA or Remission Based on CDAI and SDAI at Each Visit During Period 2.	CDAI: Remission: Baseline (N= 163, 168)	0.0 Percentage of participants
Etanercept	Percentage of Participants Achieving LDA or Remission Based on CDAI and SDAI at Each Visit During Period 2.	CDAI: LDA Week 24 (N= 163, 168)	93.9 Percentage of participants
Etanercept	Percentage of Participants Achieving LDA or Remission Based on CDAI and SDAI at Each Visit During Period 2.	CDAI: LDA Week 28 (N= 163, 168)	76.1 Percentage of participants
Etanercept	Percentage of Participants Achieving LDA or Remission Based on CDAI and SDAI at Each Visit During Period 2.	CDAI: LDA Week 36 (N= 163, 168)	71.2 Percentage of participants
Etanercept	Percentage of Participants Achieving LDA or Remission Based on CDAI and SDAI at Each Visit During Period 2.	CDAI: LDA Week 44 (N= 163, 168)	70.6 Percentage of participants
Etanercept	Percentage of Participants Achieving LDA or Remission Based on CDAI and SDAI at Each Visit During Period 2.	CDAI: LDA Week 52 (N= 163, 168)	66.9 Percentage of participants
Etanercept	Percentage of Participants Achieving LDA or Remission Based on CDAI and SDAI at Each Visit During Period 2.	CDAI: LDA Baseline (N= 163, 168)	0.6 Percentage of participants
Etanercept	Percentage of Participants Achieving LDA or Remission Based on CDAI and SDAI at Each Visit During Period 2.	CDAI: Remission: Week 24 (N= 163, 168)	16.6 Percentage of participants
Etanercept	Percentage of Participants Achieving LDA or Remission Based on CDAI and SDAI at Each Visit During Period 2.	CDAI: Remission: Week 28 (N= 163, 168)	14.7 Percentage of participants
Etanercept	Percentage of Participants Achieving LDA or Remission Based on CDAI and SDAI at Each Visit During Period 2.	CDAI: Remission: Week 36 (N= 163, 168)	20.9 Percentage of participants
Etanercept	Percentage of Participants Achieving LDA or Remission Based on CDAI and SDAI at Each Visit During Period 2.	CDAI: Remission: Week 44 (N= 163, 168)	22.1 Percentage of participants
Etanercept	Percentage of Participants Achieving LDA or Remission Based on CDAI and SDAI at Each Visit During Period 2.	CDAI: Remission: Week 52 (N= 163, 168)	20.9 Percentage of participants
Etanercept	Percentage of Participants Achieving LDA or Remission Based on CDAI and SDAI at Each Visit During Period 2.	SDAI: LDA: Baseline (N= 163, 168)	0.6 Percentage of participants
Etanercept	Percentage of Participants Achieving LDA or Remission Based on CDAI and SDAI at Each Visit During Period 2.	SDAI: LDA: Week 24 (N= 163, 168)	90.2 Percentage of participants
Etanercept	Percentage of Participants Achieving LDA or Remission Based on CDAI and SDAI at Each Visit During Period 2.	SDAI: LDA: Week 28 (N= 160, 166)	73.1 Percentage of participants
Etanercept	Percentage of Participants Achieving LDA or Remission Based on CDAI and SDAI at Each Visit During Period 2.	SDAI: LDA: Week 36 (N= 162, 167)	69.8 Percentage of participants
Etanercept	Percentage of Participants Achieving LDA or Remission Based on CDAI and SDAI at Each Visit During Period 2.	SDAI: LDA: Week 44 (N= 162, 167)	69.8 Percentage of participants
Etanercept	Percentage of Participants Achieving LDA or Remission Based on CDAI and SDAI at Each Visit During Period 2.	SDAI: LDA: Week 52 (N= 162, 167)	69.8 Percentage of participants
Etanercept	Percentage of Participants Achieving LDA or Remission Based on CDAI and SDAI at Each Visit During Period 2.	SDAI: Remission: Baseline (N= 163, 168)	0.0 Percentage of participants
Etanercept	Percentage of Participants Achieving LDA or Remission Based on CDAI and SDAI at Each Visit During Period 2.	SDAI: Remission: Week 24 (N= 163, 168)	20.9 Percentage of participants
Etanercept	Percentage of Participants Achieving LDA or Remission Based on CDAI and SDAI at Each Visit During Period 2.	SDAI: Remission: Week 28 (N= 160, 166)	16.3 Percentage of participants
Etanercept	Percentage of Participants Achieving LDA or Remission Based on CDAI and SDAI at Each Visit During Period 2.	SDAI: Remission: Week 36 (N= 162, 167)	22.8 Percentage of participants
Etanercept	Percentage of Participants Achieving LDA or Remission Based on CDAI and SDAI at Each Visit During Period 2.	SDAI: Remission: Week 44 (N= 162, 167)	22.2 Percentage of participants
Etanercept	Percentage of Participants Achieving LDA or Remission Based on CDAI and SDAI at Each Visit During Period 2.	SDAI: Remission: Week 52 (N= 162, 167)	25.3 Percentage of participants
Placebo	Percentage of Participants Achieving LDA or Remission Based on CDAI and SDAI at Each Visit During Period 2.	SDAI: Remission: Week 44 (N= 162, 167)	13.2 Percentage of participants
Placebo	Percentage of Participants Achieving LDA or Remission Based on CDAI and SDAI at Each Visit During Period 2.	CDAI: LDA Baseline (N= 163, 168)	0.0 Percentage of participants
Placebo	Percentage of Participants Achieving LDA or Remission Based on CDAI and SDAI at Each Visit During Period 2.	SDAI: LDA: Baseline (N= 163, 168)	0.0 Percentage of participants
Placebo	Percentage of Participants Achieving LDA or Remission Based on CDAI and SDAI at Each Visit During Period 2.	CDAI: LDA Week 24 (N= 163, 168)	90.5 Percentage of participants
Placebo	Percentage of Participants Achieving LDA or Remission Based on CDAI and SDAI at Each Visit During Period 2.	SDAI: Remission: Baseline (N= 163, 168)	0.0 Percentage of participants
Placebo	Percentage of Participants Achieving LDA or Remission Based on CDAI and SDAI at Each Visit During Period 2.	CDAI: LDA Week 28 (N= 163, 168)	57.7 Percentage of participants
Placebo	Percentage of Participants Achieving LDA or Remission Based on CDAI and SDAI at Each Visit During Period 2.	SDAI: LDA: Week 24 (N= 163, 168)	86.9 Percentage of participants
Placebo	Percentage of Participants Achieving LDA or Remission Based on CDAI and SDAI at Each Visit During Period 2.	CDAI: LDA Week 36 (N= 163, 168)	47.0 Percentage of participants
Placebo	Percentage of Participants Achieving LDA or Remission Based on CDAI and SDAI at Each Visit During Period 2.	SDAI: Remission: Week 36 (N= 162, 167)	12.6 Percentage of participants
Placebo	Percentage of Participants Achieving LDA or Remission Based on CDAI and SDAI at Each Visit During Period 2.	CDAI: LDA Week 44 (N= 163, 168)	43.5 Percentage of participants
Placebo	Percentage of Participants Achieving LDA or Remission Based on CDAI and SDAI at Each Visit During Period 2.	SDAI: LDA: Week 28 (N= 160, 166)	55.4 Percentage of participants
Placebo	Percentage of Participants Achieving LDA or Remission Based on CDAI and SDAI at Each Visit During Period 2.	CDAI: LDA Week 52 (N= 163, 168)	42.9 Percentage of participants
Placebo	Percentage of Participants Achieving LDA or Remission Based on CDAI and SDAI at Each Visit During Period 2.	SDAI: Remission: Week 24 (N= 163, 168)	17.9 Percentage of participants
Placebo	Percentage of Participants Achieving LDA or Remission Based on CDAI and SDAI at Each Visit During Period 2.	CDAI: Remission: Baseline (N= 163, 168)	0.0 Percentage of participants
Placebo	Percentage of Participants Achieving LDA or Remission Based on CDAI and SDAI at Each Visit During Period 2.	SDAI: LDA: Week 36 (N= 162, 167)	42.5 Percentage of participants
Placebo	Percentage of Participants Achieving LDA or Remission Based on CDAI and SDAI at Each Visit During Period 2.	CDAI: Remission: Week 24 (N= 163, 168)	14.3 Percentage of participants
Placebo	Percentage of Participants Achieving LDA or Remission Based on CDAI and SDAI at Each Visit During Period 2.	SDAI: Remission: Week 52 (N= 162, 167)	13.2 Percentage of participants
Placebo	Percentage of Participants Achieving LDA or Remission Based on CDAI and SDAI at Each Visit During Period 2.	CDAI: Remission: Week 28 (N= 163, 168)	14.3 Percentage of participants
Placebo	Percentage of Participants Achieving LDA or Remission Based on CDAI and SDAI at Each Visit During Period 2.	SDAI: LDA: Week 44 (N= 162, 167)	42.5 Percentage of participants
Placebo	Percentage of Participants Achieving LDA or Remission Based on CDAI and SDAI at Each Visit During Period 2.	CDAI: Remission: Week 36 (N= 163, 168)	12.5 Percentage of participants
Placebo	Percentage of Participants Achieving LDA or Remission Based on CDAI and SDAI at Each Visit During Period 2.	SDAI: Remission: Week 28 (N= 160, 166)	16.3 Percentage of participants
Placebo	Percentage of Participants Achieving LDA or Remission Based on CDAI and SDAI at Each Visit During Period 2.	CDAI: Remission: Week 44 (N= 163, 168)	12.5 Percentage of participants
Placebo	Percentage of Participants Achieving LDA or Remission Based on CDAI and SDAI at Each Visit During Period 2.	SDAI: LDA: Week 52 (N= 162, 167)	37.7 Percentage of participants
Placebo	Percentage of Participants Achieving LDA or Remission Based on CDAI and SDAI at Each Visit During Period 2.	CDAI: Remission: Week 52 (N= 163, 168)	11.9 Percentage of participants

Comparison: CDAI: LDA Baselinep-value: 0.35895% CI: [-0.59, 1.81]Cochran-Mantel-Haenszel

Comparison: CDAI: LDA: Week 24p-value: 0.34195% CI: [-2.38, 9.16]Cochran-Mantel-Haenszel

Comparison: CDAI: LDA: Week 28p-value: 0.00495% CI: [8.4, 28.27]Cochran-Mantel-Haenszel

Comparison: CDAI: LDA: Week 36p-value: <0.00195% CI: [13.88, 34.4]Cochran-Mantel-Haenszel

Comparison: CDAI: LDA: Week 44p-value: <0.00195% CI: [16.85, 37.35]Cochran-Mantel-Haenszel

Comparison: CDAI: LDA: Week 52p-value: <0.00195% CI: [13.61, 34.42]Cochran-Mantel-Haenszel

Comparison: CDAI: Remission: Week 24p-value: 0.77495% CI: [-5.5, 10.06]Cochran-Mantel-Haenszel

Comparison: CDAI: Remission: Week 28p-value: 0.64595% CI: [-7.15, 8.03]Cochran-Mantel-Haenszel

Comparison: CDAI: Remission: Week 36p-value: 0.0895% CI: [0.36, 16.35]Cochran-Mantel-Haenszel

Comparison: CDAI: Remission: Week 44p-value: 0.02595% CI: [1.49, 17.68]Cochran-Mantel-Haenszel

Comparison: CDAI: Remission: Week 52p-value: 0.08895% CI: [1.02, 16.88]Cochran-Mantel-Haenszel

Comparison: SDAI: LDA: Baselinep-value: 0.35895% CI: [-0.59, 1.81]Cochran-Mantel-Haenszel

Comparison: SDAI: LDA: Week 24p-value: 0.25895% CI: [-3.57, 10.13]Cochran-Mantel-Haenszel

Comparison: SDAI: LDA: Week 28p-value: 0.00595% CI: [7.49, 27.92]Cochran-Mantel-Haenszel

Comparison: SDAI: LDA: Week 36p-value: <0.00195% CI: [16.93, 37.55]Cochran-Mantel-Haenszel

Comparison: SDAI: LDA: Week 44p-value: <0.00195% CI: [21.83, 42.23]Cochran-Mantel-Haenszel

Comparison: SDAI: LDA: Week 52p-value: <0.00195% CI: [18, 38.69]Cochran-Mantel-Haenszel

Comparison: SDAI: Remission: Week 24p-value: 0.67295% CI: [-5.51, 11.51]Cochran-Mantel-Haenszel

Comparison: SDAI: Remission: Week 28p-value: 0.55695% CI: [-8.03, 8]Cochran-Mantel-Haenszel

Comparison: SDAI: Remission: Week 36p-value: 0.02295% CI: [2.07, 18.45]Cochran-Mantel-Haenszel

Comparison: SDAI: Remission: Week 44p-value: 0.04795% CI: [0.85, 17.25]Cochran-Mantel-Haenszel

Comparison: SDAI: Remission: Week 52p-value: 0.03195% CI: [3.7, 20.57]Cochran-Mantel-Haenszel

Secondary

Percentage of Participants Achieving LDA or Remission Based on Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI) at Each Visit During Period 1.

Time frame: Baseline, Weeks 4, 8, 16 and 24

Population: The FAS for Period 1 (Open Label FAS) included all randomized participants who had at least one dose of open label study drug during Period 1 (ie, ETN or MTX).

Arm	Measure	Group	Value (NUMBER)
Etanercept	Percentage of Participants Achieving LDA or Remission Based on Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI) at Each Visit During Period 1.	CDAI: LDA Baseline (N= 478)	0.4 Percentage of participants
Etanercept	Percentage of Participants Achieving LDA or Remission Based on Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI) at Each Visit During Period 1.	CDAI: LDA Week 4 (N= 473)	16.7 Percentage of participants
Etanercept	Percentage of Participants Achieving LDA or Remission Based on Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI) at Each Visit During Period 1.	CDAI: LDA Week 8 (N= 473)	33.8 Percentage of participants
Etanercept	Percentage of Participants Achieving LDA or Remission Based on Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI) at Each Visit During Period 1.	CDAI: LDA Week 16 (N= 473)	53.9 Percentage of participants
Etanercept	Percentage of Participants Achieving LDA or Remission Based on Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI) at Each Visit During Period 1.	CDAI: LDA Week 24 (N= 473)	75.7 Percentage of participants
Etanercept	Percentage of Participants Achieving LDA or Remission Based on Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI) at Each Visit During Period 1.	CDAI: Remission: Baseline (N= 478)	0.0 Percentage of participants
Etanercept	Percentage of Participants Achieving LDA or Remission Based on Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI) at Each Visit During Period 1.	CDAI: Remission: Week 4 (N= 473)	0.4 Percentage of participants
Etanercept	Percentage of Participants Achieving LDA or Remission Based on Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI) at Each Visit During Period 1.	CDAI: Remission: Week 8 (N= 473)	1.7 Percentage of participants
Etanercept	Percentage of Participants Achieving LDA or Remission Based on Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI) at Each Visit During Period 1.	CDAI: Remission: Week 16 (N= 473)	6.1 Percentage of participants
Etanercept	Percentage of Participants Achieving LDA or Remission Based on Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI) at Each Visit During Period 1.	CDAI: Remission: Week 24 (N= 473)	10.8 Percentage of participants
Etanercept	Percentage of Participants Achieving LDA or Remission Based on Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI) at Each Visit During Period 1.	SDAI: LDA: Baseline (N= 478)	0.2 Percentage of participants
Etanercept	Percentage of Participants Achieving LDA or Remission Based on Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI) at Each Visit During Period 1.	SDAI: LDA: Week 4 (N= 465)	16.1 Percentage of participants
Etanercept	Percentage of Participants Achieving LDA or Remission Based on Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI) at Each Visit During Period 1.	SDAI: LDA: Week 8 (N= 471)	32.5 Percentage of participants
Etanercept	Percentage of Participants Achieving LDA or Remission Based on Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI) at Each Visit During Period 1.	SDAI: LDA: Week 16 (N= 472)	52.3 Percentage of participants
Etanercept	Percentage of Participants Achieving LDA or Remission Based on Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI) at Each Visit During Period 1.	SDAI: LDA: Week 24 (N= 472)	72.5 Percentage of participants
Etanercept	Percentage of Participants Achieving LDA or Remission Based on Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI) at Each Visit During Period 1.	SDAI: Remission: Baseline (N= 478)	0.0 Percentage of participants
Etanercept	Percentage of Participants Achieving LDA or Remission Based on Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI) at Each Visit During Period 1.	SDAI: Remission: Week 4 (N= 465)	0.6 Percentage of participants
Etanercept	Percentage of Participants Achieving LDA or Remission Based on Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI) at Each Visit During Period 1.	SDAI: Remission: Week 8 (N= 471)	1.9 Percentage of participants
Etanercept	Percentage of Participants Achieving LDA or Remission Based on Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI) at Each Visit During Period 1.	SDAI: Remission: Week 16 (N= 472)	6.8 Percentage of participants
Etanercept	Percentage of Participants Achieving LDA or Remission Based on Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI) at Each Visit During Period 1.	SDAI: Remission: Week 24 (N= 472)	14.0 Percentage of participants

Secondary

Percentage of Participants Achieving Remission (DAS28-ESR and DAS28-CRP) at Each Visit During Period 1

Proportion of participants who achieved remission (DAS28-ESR and DAS28-CRP at each visit during period 1 is presented below.

Time frame: Baseline, Weeks 4, 8, 16 and 24

Population: The FAS for Period 1 (Open Label FAS) included all randomized participants who had at least one dose of open label study drug during Period 1 (ie, ETN or MTX).

Arm	Measure	Group	Value (NUMBER)
Etanercept	Percentage of Participants Achieving Remission (DAS28-ESR and DAS28-CRP) at Each Visit During Period 1	DAS28-ESR Week 4 (N= 473)	4.0 Percentage of participants
Etanercept	Percentage of Participants Achieving Remission (DAS28-ESR and DAS28-CRP) at Each Visit During Period 1	DAS28-CRP Week 4 (N= 465)	9.0 Percentage of participants
Etanercept	Percentage of Participants Achieving Remission (DAS28-ESR and DAS28-CRP) at Each Visit During Period 1	DAS28-ESR Week 8 (N= 473)	8.9 Percentage of participants
Etanercept	Percentage of Participants Achieving Remission (DAS28-ESR and DAS28-CRP) at Each Visit During Period 1	DAS28-CRP Week 8 (N= 471)	17.8 Percentage of participants
Etanercept	Percentage of Participants Achieving Remission (DAS28-ESR and DAS28-CRP) at Each Visit During Period 1	DAS28-ESR Week 16 (N= 473)	13.5 Percentage of participants
Etanercept	Percentage of Participants Achieving Remission (DAS28-ESR and DAS28-CRP) at Each Visit During Period 1	DAS28-CRP Week 16 (N= 472)	31.1 Percentage of participants
Etanercept	Percentage of Participants Achieving Remission (DAS28-ESR and DAS28-CRP) at Each Visit During Period 1	DAS28-ESR Week 24 (N= 473)	26.6 Percentage of participants
Etanercept	Percentage of Participants Achieving Remission (DAS28-ESR and DAS28-CRP) at Each Visit During Period 1	DAS28-CRP Week 24 (N= 472)	49.8 Percentage of participants

Secondary

Percentage of Participants Achieving Remission (DAS28-ESR and DAS28-CRP) at Each Visit During Period 2

Proportion of participants who achieved LDA (DAS28-ESR and DAS28-CRP at each visit during period 2 is presented below.

Time frame: Baseline, Weeks 24, 28, 36, 44 and 52

Arm	Measure	Group	Value (NUMBER)
Etanercept	Percentage of Participants Achieving Remission (DAS28-ESR and DAS28-CRP) at Each Visit During Period 2	DAS28-CRP Baseline (N= 163, 168)	0.0 Percentage of participants
Etanercept	Percentage of Participants Achieving Remission (DAS28-ESR and DAS28-CRP) at Each Visit During Period 2	DAS28-ESR Week 36 (N= 163, 168)	31.9 Percentage of participants
Etanercept	Percentage of Participants Achieving Remission (DAS28-ESR and DAS28-CRP) at Each Visit During Period 2	DAS28-CRP Week 24 (N= 163, 168)	64.4 Percentage of participants
Etanercept	Percentage of Participants Achieving Remission (DAS28-ESR and DAS28-CRP) at Each Visit During Period 2	DAS28-CRP Week 36 (N= 162, 167)	50.0 Percentage of participants
Etanercept	Percentage of Participants Achieving Remission (DAS28-ESR and DAS28-CRP) at Each Visit During Period 2	DAS28-ESR Baseline (N= 163, 168)	0.0 Percentage of participants
Etanercept	Percentage of Participants Achieving Remission (DAS28-ESR and DAS28-CRP) at Each Visit During Period 2	DAS28-ESR Week 44 (N= 163, 168)	30.7 Percentage of participants
Etanercept	Percentage of Participants Achieving Remission (DAS28-ESR and DAS28-CRP) at Each Visit During Period 2	DAS28-ESR Week 28 (N= 163, 168)	32.5 Percentage of participants
Etanercept	Percentage of Participants Achieving Remission (DAS28-ESR and DAS28-CRP) at Each Visit During Period 2	DAS28-CRP Week 44 (N= 162, 167)	51.9 Percentage of participants
Etanercept	Percentage of Participants Achieving Remission (DAS28-ESR and DAS28-CRP) at Each Visit During Period 2	DAS28-ESR Week 24 (N= 163, 168)	38.0 Percentage of participants
Etanercept	Percentage of Participants Achieving Remission (DAS28-ESR and DAS28-CRP) at Each Visit During Period 2	DAS28-ESR Week 52 (N= 163, 168)	33.7 Percentage of participants
Etanercept	Percentage of Participants Achieving Remission (DAS28-ESR and DAS28-CRP) at Each Visit During Period 2	DAS28-CRP Week 28 (N= 160, 166)	51.9 Percentage of participants
Etanercept	Percentage of Participants Achieving Remission (DAS28-ESR and DAS28-CRP) at Each Visit During Period 2	DAS28-CRP Week 52 (N= 162, 167)	46.9 Percentage of participants
Placebo	Percentage of Participants Achieving Remission (DAS28-ESR and DAS28-CRP) at Each Visit During Period 2	DAS28-CRP Week 28 (N= 160, 166)	34.9 Percentage of participants
Placebo	Percentage of Participants Achieving Remission (DAS28-ESR and DAS28-CRP) at Each Visit During Period 2	DAS28-ESR Baseline (N= 163, 168)	0.0 Percentage of participants
Placebo	Percentage of Participants Achieving Remission (DAS28-ESR and DAS28-CRP) at Each Visit During Period 2	DAS28-CRP Baseline (N= 163, 168)	0.0 Percentage of participants
Placebo	Percentage of Participants Achieving Remission (DAS28-ESR and DAS28-CRP) at Each Visit During Period 2	DAS28-ESR Week 24 (N= 163, 168)	36.3 Percentage of participants
Placebo	Percentage of Participants Achieving Remission (DAS28-ESR and DAS28-CRP) at Each Visit During Period 2	DAS28-CRP Week 24 (N= 163, 168)	63.1 Percentage of participants
Placebo	Percentage of Participants Achieving Remission (DAS28-ESR and DAS28-CRP) at Each Visit During Period 2	DAS28-ESR Week 28 (N= 163, 168)	20.2 Percentage of participants
Placebo	Percentage of Participants Achieving Remission (DAS28-ESR and DAS28-CRP) at Each Visit During Period 2	DAS28-CRP Week 52 (N= 162, 167)	19.8 Percentage of participants
Placebo	Percentage of Participants Achieving Remission (DAS28-ESR and DAS28-CRP) at Each Visit During Period 2	DAS28-ESR Week 36 (N= 163, 168)	17.3 Percentage of participants
Placebo	Percentage of Participants Achieving Remission (DAS28-ESR and DAS28-CRP) at Each Visit During Period 2	DAS28-CRP Week 36 (N= 162, 167)	25.1 Percentage of participants
Placebo	Percentage of Participants Achieving Remission (DAS28-ESR and DAS28-CRP) at Each Visit During Period 2	DAS28-ESR Week 44 (N= 163, 168)	11.9 Percentage of participants
Placebo	Percentage of Participants Achieving Remission (DAS28-ESR and DAS28-CRP) at Each Visit During Period 2	DAS28-CRP Week 44 (N= 162, 167)	21.0 Percentage of participants
Placebo	Percentage of Participants Achieving Remission (DAS28-ESR and DAS28-CRP) at Each Visit During Period 2	DAS28-ESR Week 52 (N= 163, 168)	13.1 Percentage of participants

Comparison: DAS28-CRP Week 24p-value: 0.77495% CI: [-9.03, 11.68]Cochran-Mantel-Haenszel

Comparison: DAS28-ESR Week 28p-value: 0.03495% CI: [2.86, 21.69]Cochran-Mantel-Haenszel

Comparison: DAS28-CRP Week 28p-value: 0.0295% CI: [6.33, 27.54]Cochran-Mantel-Haenszel

Comparison: DAS28-ESR Week 36p-value: 0.00795% CI: [5.48, 23.8]Cochran-Mantel-Haenszel

Comparison: DAS28-CRP Week 36p-value: <0.00195% CI: [14.72, 34.98]Cochran-Mantel-Haenszel

Comparison: DAS28-ESR Week 44p-value: <0.00195% CI: [10.16, 27.38]Cochran-Mantel-Haenszel

Comparison: DAS28-CRP Week 44p-value: <0.00195% CI: [21.03, 40.76]Cochran-Mantel-Haenszel

Comparison: DAS28-ESR Week 52p-value: <0.00195% CI: [11.78, 29.52]Cochran-Mantel-Haenszel

Comparison: DAS28-CRP Week 52p-value: <0.00195% CI: [17.38, 36.93]Cochran-Mantel-Haenszel

Secondary

Percentage of Participants Who Had a Recurrence of Disease Symptoms During Period 2, Based on the Protocol Criteria

Flare is defined as the criteria of loss of LDA plus ≥0.6 unit worsening in DAS28-ESR score during period 2.

Time frame: Baseline and Week 52

Arm	Measure	Value (NUMBER)
Etanercept	Percentage of Participants Who Had a Recurrence of Disease Symptoms During Period 2, Based on the Protocol Criteria	52.1 Percentage of participants
Placebo	Percentage of Participants Who Had a Recurrence of Disease Symptoms During Period 2, Based on the Protocol Criteria	79.8 Percentage of participants

p-value: <0.001Log Rank

Secondary

Percentage of Participants Who Remained in Remission at Week 52 (DAS28-ESR)

Proportion of participants who remained in Remission (DAS28-ESR \<2.6) at Week 52.

Time frame: Baseline and Week 52

Arm	Measure	Value (NUMBER)
Etanercept	Percentage of Participants Who Remained in Remission at Week 52 (DAS28-ESR)	53.2 Percentage of participants
Placebo	Percentage of Participants Who Remained in Remission at Week 52 (DAS28-ESR)	29.5 Percentage of participants

p-value: 0.01995% CI: [6.83, 40.61]Cochran-Mantel-Haenszel

Source: ClinicalTrials.gov · Data processed: Mar 9, 2026

Study Conducted in Subjects With Rheumatoid Arthritis Who Have Moderate to Severe Disease Activity Despite Methotrexate Therapy With or Without Other Non Biologic Disease Modifying Antirheumatic Drugs (DMARDs)for at Least 12 Weeks Prior to Screening

Conditions

Keywords

Brief summary

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Countries

Participant flow

Recruitment details

Pre-assignment details

Participants by arm

Withdrawals & dropouts

Baseline characteristics

Adverse events

Outcome results

Percentage of Participants Who Remained in Low Disease Activity (LDA) (Disease Activity Score in 28 Joints-erythrocyte Sedimentation Rate [DAS28-ESR] <3.2) at Week 52.

Change From Baseline in DAS28-CRP and DAS28-ESR in Period 1

Change From Baseline in DAS28-CRP and DAS28-ESR in Period 2

Change in CRP and ESR at Each Visit During Period 1

Change in CRP and ESR at Each Visit During Period 2

Change in Morning Stiffness (Measured in Minutes) at Each Visit During Period 1

Change in Morning Stiffness (Measured in Minutes) at Each Visit During Period 2

Change in the Physician Global Assessment of Arthritis at Each Visit During Period 1

Change in the Physician Global Assessment of Arthritis at Each Visit During Period 2

Change in the Subject General Health VAS and Pain VAS at Each Visit During Period 2

Change in the Subject General Health Visual Analog Scale (VAS) and Pain VAS at Each Visit During Period 1

Change in the Subject Global Assessment of Arthritis in Period 1

Change in the Subject Global Assessment of Arthritis in Period 2

Change in the Tender and Swollen Joint Counts at Each Visit During Period 1 (Using 28 Joint Count as Well as 66/68 Joint Counts).

Change in the Tender and Swollen Joint Counts at Each Visit During Period 2 (Using 28 Joint Count as Well as 66/68 Joint Counts).

Change of CDAI and SDAI at Each Visit During Period 1.

Change of CDAI and SDAI at Each Visit During Period 2

Percentage of Participants Achieving ACR20, ACR50, ACR70 and ACR90 (by 66/68 Joint Counts) During Period 2 at Each Visit.

Percentage of Participants Achieving American College of Rheumatology (ACR) ACR20, ACR50, ACR70 and ACR90 (by 66/68 Joint Counts) During Period 1 at Each Visit.

Percentage of Participants Achieving EULAR Good and or Moderate Responses (by Both DAS28-ESR and DAS28-CRP Scores) at Each Visit During Period 2.

Percentage of Participants Achieving European League Against Rheumatism (EULAR) Good and or Moderate Responses (by Both DAS28-ESR and DAS28-CRP Scores) at Each Visit During Period 1.

Percentage of Participants Achieving LDA (DAS28-ESR and DAS28-C-reactive Protein [CRP]) at Each Visit During Period 1

Percentage of Participants Achieving LDA (DAS28-ESR and DAS28-CRP) at Each Visit During Period 2

Percentage of Participants Achieving LDA or Remission Based on CDAI and SDAI at Each Visit During Period 2.

Percentage of Participants Achieving LDA or Remission Based on Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI) at Each Visit During Period 1.

Percentage of Participants Achieving Remission (DAS28-ESR and DAS28-CRP) at Each Visit During Period 1

Percentage of Participants Achieving Remission (DAS28-ESR and DAS28-CRP) at Each Visit During Period 2

Percentage of Participants Who Had a Recurrence of Disease Symptoms During Period 2, Based on the Protocol Criteria

Percentage of Participants Who Remained in Remission at Week 52 (DAS28-ESR)