Study of Etanercept in Subjects With Rheumatoid Arthritis Who Have Had an Inadequate Response to Adalimumab or Infliximab Plus Methotrexate

Change From Baseline in the DAS28 at Week 24

DAS28 calculated from the number of SJC and PJC using the 28 joints count, the CRP and and Subject General Health VAS assessment (participant rated health assessment with scores ranging 0 to 100; higher scores indicate worse health status).

Time frame: Baseline, 24 weeks

Number of Participants With DAS28 <3.2

Number of participants with DAS28 \<3.2. A score of \< 3.2 implied low disease activity.

Time frame: 12 weeks, 24 weeks

Number of Participants With DAS28 <2.6

Number of Participants with DAS28 \<2.6. A DAS28 \< 2.6 implies remission.

Time frame: 12 weeks, 24 weeks

Number of Participants Achieving American College of Rheumatology 20% (ACR20) Response

ACR20 response: greater than or equal to (≥) 20 percent (%) improvement in tender joint count; ≥ 20% improvement in swollen joint count; and ≥ 20% improvement in at least 3 of 5 remaining ACR core measures: participant's assessment of pain; Subject Global Assessment (SGA) of disease activity; Physician Global Assessment (PGA) of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire \[HAQ\]); and CRP.

Time frame: 12 weeks, 24 weeks

Number of Participants Achieving American College of Rheumatology 50% (ACR50) Response

ACR50 response: greater than or equal to (≥) 50 percent (%) improvement in tender or swollen joint counts and ≥ 50% improvement in 3 of the 5 remaining ACR core measures: participant's assessment of pain; SGA of disease activity; PGA of disease activity; subject's assessment of functional disability via a HAQ; and CRP.

Time frame: 12 weeks, 24 weeks

Number of Participants Achieving American College of Rheumatology 70% (ACR70) Response

ACR70 response: greater than or equal to (≥) 70 percent (%) improvement in tender or swollen joint counts and ≥ 70% improvement in 3 of the 5 remaining ACR core measures: participant's assessment of pain; SGA of disease activity; PGA of disease activity; subject's assessment of functional disability via a HAQ; and CRP.

Time frame: 12 weeks, 24 weeks

Number of Participants Achieving American College of Rheumatology 90% (ACR90) Response

ACR90 response: greater than or equal to (≥) 90 percent (%) improvement in tender or swollen joint counts and ≥ 90% improvement in 3 of the 5 remaining ACR core measures: participant's assessment of pain; SGA of disease activity; PGA of disease activity; subject's assessment of functional disability via a HAQ; and CRP.

Time frame: 12 weeks, 24 weeks

Number of Participants Achieving European League Against Rheumatism (EULAR) Good and/or Moderate Response.

The Disease Activity Score Based on 28-joints Count based (DAS28-based) EULAR response criteria were used to measure individual response as none, good, and moderate, depending on the extent of change from baseline and the level of disease activity reached. Good responders: change from baseline \>1.2 with DAS28 =\< 3.2; moderate responders: change from baseline \>1.2 with DAS28 \>3.2 to =\<5.1 or change from baseline \>0.6 to =\<1.2 with DAS28 =\<5.1; non-responders: change from baseline =\< 0.6 or change from baseline \>0.6 and =\<1.2 with DAS28 \>5.1.

Time frame: 12 weeks, 24 weeks

Number of Participants Achieving Low Disease Activity or Remission Based on Clinical Disease Activity Index (CDAI)

The CDAI is the numerical sum of 4 outcome parameters: tender joint count (TJC) and SJC based on a 28-joint assessment, SGA and PGA assessed on 0-10 point scale; higher scores=greater affliction due to disease activity. CDAI total score = 0-76. CDAI \<= 2.8 indicates disease remission, \>2.8 to 10 = low disease activity, \>10 to 22 = moderate disease activity, and \>22 = high disease activity.

Time frame: 12 weeks, 24 weeks

Number of Participants Achieving Low Disease Activity or Remission Based on Simplified Disease Activity Index (SDAI).

The SDAI is the numerical sum of five outcome parameters: TJC) and SJC based on a 28-joint assessment, SGA and PGA assessed on 0-10 point scale; higher scores=greater affliction due to disease activity, and CRP (mg/dL). SDAI total score= 0-86. SDAI \<=3.3 indicates disease remission, \>3.4 to 11 = low disease activity, \>11 to 26 = moderate disease activity, and \>26 = high disease activity.

Time frame: 12 weeks, 24 weeks

Change From Baseline in CDAI

Change from Baseline in CDAI scores was to be calculated. The CDAI is the numerical sum of 4 outcome parameters: TJC and SJC based on a 28-joint assessment, SGA and PGA assessed on 0-10 point scale; higher scores=greater affliction due to disease activity. CDAI total score = 0-76. CDAI \<= 2.8 indicates disease remission, \>2.8 to 10 = low disease activity, \>10 to 22 = moderate disease activity, and \>22 = high disease activity.

Time frame: Baseline, 12 weeks, 24 weeks

Change From Baseline in SDAI.

Change from Baseline in SDAI scores were to be calculated. The SDAI is the numerical sum of five outcome parameters: TJC and SJC based on a 28-joint assessment, SGA and PGA assessed on 0-10 point scale; higher scores=greater affliction due to disease activity, and CRP (mg/dL). SDAI total score= 0-86. SDAI \<=3.3 indicates disease remission, \>3.4 to 11 = low disease activity, \>11 to 26 = moderate disease activity, and \>26 = high disease activity.

Time frame: Baseline, 12 weeks, 24 weeks

Change From Baseline in Number of Tender/Painful Joints

Change from Baseline in the number of tender/painful joints using the 28 joint count including shoulders, elbows, wrists, metacarpophalangeal joints, proximal interphalangeal joints, and knees was to be calculated.

Time frame: Baseline, 12 weeks, 24 weeks

Change From Baseline in Number of Swollen Joints

Change from Baseline in the number of swollen joints including shoulders, elbows, wrists, metacarpophalangeal joints, proximal interphalangeal joints, and knees was to be calculated.

Time frame: Baseline, 12 weeks, 24 weeks

Change From Baseline in Physician Global Assessment of Disease Activity

Change from Baseline in the PGA scores was to be estimated. The Study Physician estimated the participant's overall disease activity over the last 2 to 3 days using a scale between 0 (no disease activity) and 10 (extreme disease activity).

Time frame: Baseline, 12 weeks, 24 weeks

Change From Baseline in Subject Global Assessment of Disease Activity

Change from Baseline in Subject Global Assessment of Disease Activity was to be estimated. Participants were to assess their overall disease activity over the last 2 to 3 days using a scale between 0 (no disease activity) and 10 (extreme disease activity).

Time frame: Baseline, 12 weeks, 24 weeks

Change From Baseline in Subject General Health VAS.

Subject General Health VAS assessment (participant rated health assessment with scores ranging 0 to 100; higher scores indicate worse health status).

Time frame: Baseline, 12 weeks, 24 weeks

Change From Baseline in Subject Pain

Subject Pain was to be measured on a 0 to 100 mm Visual Analog Scale (VAS), with 0 mm = no pain and 100 mm = most severe pain.

Time frame: Baseline, 12 weeks, 24 weeks

Change From Baseline in CRP

The test for CRP is a laboratory measurement for evaluation of an acute phase reactant of inflammation through the use of an ultrasensitive assay. A decrease in the level of CRP indicates reduction in inflammation and therefore improvement.

Time frame: Baseline, 12 weeks, 24 weeks

Change From Baseline in Health Assessment Questionnaire Disability and Discomfort Scales (HAQ-DI)

Health Assessment Questionnaire-Disability Index (HAQ-DI): participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty.

Time frame: Baseline, 12 weeks, 24 weeks

Change From Baseline in Euro Quality of Life (Qol) EQ-5 Dimensions Questionnaire (EQ-5D)

The EuroQol-5 Dimensions (EQ-5D) is a participant-completed questionnaire designed to assess health related quality of life. There are 2 components to the EQ-5D: a Health State Profile and a VAS. For the Health State Profile, participants recorded their level of current health for 5 domains comprising a health profile: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Scores from the 5 domains may be used to calculate a single index value, also known as a utility score. On the VAS participants were asked to rate their current health on a scale from 0 to 100 mm, where 0 represented the "worst imaginable health state" and 100 represented the "best imaginable health state." In addition to a summary of mean changes, 1 categorical endpoint each based on EQ-5D utility score and 1 based on the VAS were derived and analyzed: EQ-5D utility score improvement ≥0.05 and EQ-5D VAS score \>82.

Time frame: Baseline, 12 weeks, 24 weeks

Change From Baseline in Short Form-36 Health Survey (SF-36)

The 36-Item Short Form Health Survey (SF-36) is widely used 36-item questionnaire that measures general health-related quality of life in the following 8 domains: physical function, role limitations due to physical health, bodily pain, general health perception, vitality, social functioning, role limitation due to emotional problems, and mental health. Scores for the 8 domains range from 0 to 100 where higher scores are better.

Time frame: Baseline, 12 weeks, 24 weeks

Change From Baseline in Patient Acceptable Symptom State (PASS)

The Patient Acceptable Symptom State (PASS) was a participant-completed form in which participants were asked to "Think about all the ways your rheumatoid arthritis (RA) has affected you during the last 48 hours. If you were to remain in the next few months as you were during the last 48 hours, would this be acceptable or unacceptable to you?" The participant indicated a response of either "acceptable" or "unacceptable".

Time frame: Baseline, 12 weeks, 24 weeks

Change From Baseline in Vectra Disease Activity Levels

The change from Baseline in Vectra disease activity levels was to be estimated. The assessment measures serum protein biomarkers associated with RA. It has a range from 1-100 with lower scores indicating the better outcome.

Time frame: Baseline, 12 weeks, 24 weeks

Number of Participants With Positive Etanercept Anti-drug Antibody Status

Blood samples (6 mL) were collected at the baseline, Week 12, and Week 24 visits, or upon early withdrawal, to provide a minimum of 1 mL serum each for ETN ADA and ETN neutralizing antibody analyses. Samples which were positive for ETN anti-drug antibodies were then also tested for ETN neutralizing antibodies.

Time frame: Baseline, 12 weeks, 24 weeks

Number of Participants With Positive Etanercept Neutralizing Anti-drug Antibody Status

Blood samples (6 mL) were collected at the baseline, Week 12, and Week 24 visits, or upon early withdrawal, to provide a minimum of 1 mL serum each for ETN ADA and ETN neutralizing antibody analyses. Samples which were positive for ETN anti-drug antibodies were then also tested for ETN neutralizing antibodies.

Time frame: Baseline, 12 weeks, 24 weeks