Study Comparing The Effect On Disease Activity When Reducing Or Discontinuing Etanercept In Subjects With RA

A participant was considered as non-failure if the calculated DAS28 <=3.2 at all visits or if the calculated DAS28 >3.2, the increase of calculated DAS28 from randomization (Week 0): was <0.6 at all visit or was >=0.6 but <1.2 on no more than 1 consecutive visit. Percentage of participants who were non-failures calculated based on DAS28 and disease progression as determined by investigator or participant.

TTF (in weeks): (date of failure minus date of randomization) divided by 7. Date of failure was ordinary visit date or extra visit date in case of failure (extra visit was within 2 weeks from the date a participant experienced significant disease progression between visits and wanted to withdraw from Period 2), or date of withdrawal due to disease progression. Participants who did not have a treatment failure were censored at their last evaluation visit. Participants who withdrew from the study prematurely and did not have a treatment failure were censored on the date of their withdrawal.

Participants who had DAS28 less than or equal to (<=) 3.2 were considered in remission or LDA state.

Participants who had DAS28 <=3.2 were considered in remission or LDA state. Percentage of visits during which a participant was in remission or LDA state was calculated as number of visits in which participant was in remission or LDA divided by total number of visits multiplied by 100.

DAS28 calculated from the number of swollen joints (SJC) and painful joints (PJC) using the 28 joints count, the erythrocyte sedimentation rate (ESR) (millimeters per hour [mm/hour]) and patient's global assessment (PtGA) of disease activity (participant rated arthritis activity assessment with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity). DAS28 <=3.2 implied low disease activity, DAS28 >3.2 to 5.1 = moderate to high disease activity and less than (<) 2.6=remission.

DAS28 calculated from SJC and PJC using the 28 joints count, the ESR (mm/hour) and PtGA of disease activity (participant rated arthritis activity assessment with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity). DAS28 <=3.2 = low disease activity, DAS28 >3.2 to 5.1 = moderate to high disease activity and <2.6=remission.

Number of tender joints was determined by examining 28 joints and identified the joints that were painful under pressure or to passive motion. The number of tender joints was recorded on the joint assessment form at each visit, no tenderness = 0, tenderness = 1. A negative value in change from randomization indicates an improvement.

Number of swollen joints was determined by examination of 28 joints and identifying when swelling was present. The number of swollen joints was recorded on the joint assessment form at each visit, no swelling = 0, swelling =1. A negative value in change from randomization indicates an improvement.

PGA of disease activity was measured on a 0 to 100 millimeter (mm) Visual Analog Scale (VAS), with 0 mm = no disease activity and 100 mm = extreme disease activity.

Participants assessed the overall activity of their rheumatoid arthritis (RA) on a 0 to 100 mm VAS, where 0 mm = no disease activity and 100 mm = extreme disease activity.

Participants answered "in general how would you rate your health over the last 2-3 weeks?" Participants responded by using a 0 to 100 mm VAS, where 0 mm = very well and 100 mm = extremely bad.

Participants answered "in general how would you rate your health over the last 2-3 weeks?" Participants responded by using a 0 to 100 mm VAS, where 0 mm = very well and 100 mm = extremely bad.

Participants indicated the amount of pain experience during the last 2-3 days by marking a vertical line on 100 mm VAS. Intensity of pain range: 0 = no pain to 100 = pain as bad as it could be.

Participants indicated the amount of pain experience during the last 2-3 days by marking a vertical line on 100 mm VAS. Intensity of pain range: 0 = no pain to 100 = pain as bad as it could be.

Duration of morning stiffness: Time elapsed when participant woke up in morning and was able to resume normal activities without stiffness in minutes. The duration of morning stiffness was determined by asking the following questions: 1) Over the last 2 days, when did you wake in the morning? 2) Over the last 2 days, when were you able to resume your normal activities without stiffness? Increase in stiffness duration from randomization represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represented improvement.

ESR is a laboratory test that provides a non-specific measure of inflammation. The test assesses the rate at which red blood cells fall in a test tube. Normal range is 0-30 millimeter per hour (mm/hour). A higher rate is consistent with inflammation.

The test for CRP is a laboratory measurement for evaluation of an acute phase reactant of inflammation through the use of an ultrasensitive assay. Normal range of CRP is <10 milligram per liter (mg/L). A decrease in the level of CRP indicates reduction in inflammation and therefore improvement.

mTSS = sum of erosion and Joint Space Narrowing (JSN) scores for 44 joints (16 per hand and 6 per foot). mTSS scores ranged from 0 (normal) to 448 (worst possible total score). Change: scores at observation minus score at randomization. An increase in mTSS from randomization represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represented improvement.

MRI of hand/wrist of dominant hand scored for signs of synovitis (S-score), bone edema(O-score), bone erosions (E-score) as per outcome measures in RA clinical trials (OMERACT). S-score:0(normal)-3(severe) for distal radioulnar,radiocarpal,intercarpal-carpometacarpal,second-fifth metacarpophalangeal joints, total score(TS)0-21, higher score(HS)=severe synovitis. O-score:0(no volume increment)-3(100% volume increment) in 23 hand/wrist joints, TS 0-69, HS=more edema. E-score:0(no volume occupied by erosion)-10(100% volume occupied by erosion) in 23 hand/wrist joints, TS 0-230, HS=more erosion.

MRI of hand/wrist of dominant hand was scored for signs of synovitis (S-score), bone edema (O-score), and bone erosions (E-score) as per OMERACT. S-score: 0 (normal) to 3 (severe) for each of distal radioulnar, radiocarpal, intercarpal-carpometacarpal, second to fifth metacarpophalangeal joints; total score 0 to 21, higher score=severe synovitis.

MRI of hand/wrist of dominant hand was scored for signs of synovitis (S-score), bone edema (O-score), and bone erosions (E-score) as per OMERACT. O-score: 0 (no volume increment) to 3 (100% volume increment) in 23 hand/wrist joints; total score 0 to 69, higher scores=more edema. E-score: 0 (no volume occupied by erosion) to 10 (100% volume occupied by erosion) in 23 hand/wrist joints; total score 0 to 230, higher scores=more erosion.

Percentage of participants who were treatment failure over 48 weeks as per potentially predictor variables (at randomization) are reported: number of swollen joints/tender joints, DAS28, PGA, PtGA, participant general health VAS, participant pain VAS, clinical disease activity index (CDAI), simplified disease activity index (SDAI), ESR (mm/hour), plasma CRP (mg/L), sensitive serum CRP (mg/L), anti- cyclic citrullinated peptide (anti CCP, units/mL), cartilage oligomeric matrix protein (COMP, units/liter), S-score, O-score, E-score, Joint space narrowing score, erosion score, and mTSS.