Study of Apremilast to Evaluate the Safety and Effectiveness for Patients With Rheumatoid Arthritis

Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) at Week 24

The Health Assessment Questionnaire - Disability Index (HAQ-DI) is a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability.

Time frame: Baseline and Week 24

Change From Baseline in the Medical Outcome Study Short Form 36-item (SF-36) Physical Functioning Domain at Week 16

The Medical Outcome Study Short Form 36-Item Health Survey, Version 2 (SF-36) is a self-administered instrument that measures the impact of disease on overall quality of life and consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). The concepts measured by the SF-36 are not specific to any age, disease, or treatment group, allowing comparison of relative burden of different diseases and the relative benefit of different treatments. Norm-based scores were used in analyses, calibrated so that 50 is the average score and the standard deviation equals 10. Higher scores indicate a higher level of functioning. The physical functioning domain assesses limitations in physical activities because of health problems. A positive change from baseline score indicates an improvement.

Time frame: Baseline and Week 16

Change From Baseline in the Clinical Disease Activity Index (CDAI) at Week 16

The Clinical Disease Activity Index (CDAI) is a composite index that is calculated as the sum of the: * 28 tender joint count (TJC), * 28 swollen joint count (SJC), * Subject's Global Assessment of Disease Activity measured on a 100 mm visual analog scale (VAS), where 0 mm = lowest disease activity and 100 mm = highest; * Physician's Global Assessment of Disease Activity -measured on a 100 mm VAS, where 0 mm = lowest disease activity and 100 mm = highest. The CDAI score ranges from 0-76 where lower scores indicate less disease activity. The following thresholds of disease activity have been defined for the CDAI: Remission: ≤ 2.8; Low Disease Activity: \> 2.8 and ≤ 10; Moderate Disease Activity: \> 10 and ≤ 22; High Disease Activity: \> 22

Time frame: Baseline and Week 16

Percentage of Participants Who Achieve Low Disease Activity or Remission Based on the Clinical Disease Activity Index (CDAI) ≤ 10 at Week 16

The Clinical Disease Activity Index (CDAI) is a composite index that is calculated as the sum of the: * 28 tender joint count (TJC), * 28 swollen joint count (SJC), * Subject's Global Assessment of Disease Activity measured on a 100 mm visual analog scale (VAS), where 0 mm = lowest disease activity and 100 mm = highest; * Physician's Global Assessment of Disease Activity -measured on a 100 mm VAS, where 0 mm = lowest disease activity and 100 mm = highest. The CDAI score ranges from 0-76 where lower scores indicate less disease activity. The following thresholds of disease activity have been defined for the CDAI: Remission: ≤ 2.8; Low Disease Activity: \> 2.8 and ≤ 10; Moderate Disease Activity: \> 10 and ≤ 22; High Disease Activity: \> 22

Time frame: Baseline and Week 16

Change From Baseline in Disease Activity Score 28 (DAS28) (Using C-Reactive Protein) (CRP) at Week 16

The DAS28 measures the severity of disease at a specific time and is derived from the following variables: * 28 tender joint count (TJC28) * 28 swollen joint count (SJC28), which do not include the distal interphalangeal (DIP) joints, the hip joint, or the joints below the knee; * C-reactive protein (CRP) * Subject's global assessment of disease activity (SGA ) DAS28 values range from 2.0 to 10.0 while higher values mean a higher disease activity. A DAS28 score higher than 5.1 indicates high disease activity, a DAS28 score less than 3.2 indicates low disease activity, and a DAS28 score less than 2.6 indicates clinical remission.

Time frame: Baseline and Week 16

Percentage Change From Baseline in the Tender Joint Count at Week 16

Joint tenderness is the presence of pain in a joint when pressure is applied by the examiner to elicit tenderness. The 68 tender joint count evaluates the following joints: upper-temporomandibular, sternoclavicular, acromioclavicular, shoulder, elbow, wrist, meta-carpophalangeal, proximal interphalangeal and distal interphalangeal; lower: hip, knee, ankle, midtarsal, metatarsophalangeal and proximal interphalangeal.

Time frame: Baseline and Week 16

Percentage Change From Baseline in the Swollen Joint Count at Week 16

Joint swelling is soft tissue swelling that is detectable along the joint margins and is assessed by inspection and direct palpation of the joint, by the examiner. The ACR 66 swollen joint count evaluates the following joints: upper-temporomandibular, sternoclavicular, acromioclavicular, shoulder, elbow, wrist, metacarpophalangeal, proximal interphalangeal and distal interphalangeal; lower: knee, ankle, midtarsal, metatarsophalangeal and proximal interphalangeal.

Time frame: Baseline and Week 16

Percentage Change From Baseline in the Subject Assessment of Pain at Week 16

The Subject Assessment of Pain was measured asking the participant to place a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents "no pain," and the right-hand boundary (score = 100 mm) represents "pain as severe as can be imagined." The distance from the mark to the left-hand boundary was recorded in millimeters.

Time frame: Baseline and Week 16

Percentage Change From Baseline in the Subject Global Assessment of Disease Activity at Week 16

The Subject Global Assessment of Disease Activity was measured asking the participant to place a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents " lowest disease activity," and the right-hand boundary (score = 100 mm) represents " highest disease activity." The distance from the mark to the left-hand boundary was recorded in millimeters.

Time frame: Baseline and Week 16

Percentage Change From Baseline in the Physician Global Assessment of Disease Activity at Week 16

The Physician Global Assessment of Disease Activity was measured asking the physician to assess the subject's current arthritis disease activity by placing a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents " lowest disease activity," and the right-hand boundary (score = 100 mm) represents " highest disease activity." The distance from the mark to the left-hand boundary was recorded in millimeters.

Time frame: Baseline and Week 16

Percentage Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 16

The Health Assessment Questionnaire - Disability Index (HAQ-DI) was a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability.

Time frame: Baseline and Week 16

Percentage Change From Baseline in the High Sensitivity C-Reactive Protein (CRP) at Week 16

C-Reactive Protein (CRP) is a substance produced by the liver that increases in the presence of inflammation in the body. An elevated CRP level is identified with blood tests and is considered a non-specific "marker" for disease.

Time frame: Baseline and Week 16

Percentage Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at Week 16

The erythrocyte sedimentation rate (ESR) is a blood test that can reveal inflammatory activity. The subject's blood is placed in a tall, thin tube, red erythrocytes gradually settle to the bottom. Inflammation can cause the cells to clump together. Because these clumps of cells are denser than individual cells, they settle to the bottom more quickly. The ESR test measures the distance red blood cells fall in a test tube in one hour. The farther the red blood cells have descended, the greater the inflammatory response.

Time frame: Baseline and Week 16

Change From Baseline in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Score at Week 16

The FACIT-Fatigue scale was a 13-item self-administered questionnaire that assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means "not at all," and 4 means "very much." The FACIT-Fatigue scale score ranges from 0 to 52, with higher scores denoting lower levels of fatigue. A positive change from baseline score indicates an improvement.

Time frame: Baseline and Week 16

Percentage of Participants Who Achieve an Improvement of ≥ 0.22 Units From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 16

The Health Assessment Questionnaire - Disability Index (HAQ-DI) was a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability.

Time frame: Baseline and Week 16

Percentage of Participants Who Achieve an Improvement of at Least 4 Units From Baseline in the Functional Assessment of Chronic Illness Therapy -Fatigue (FACIT-Fatigue) at Week 16

The FACIT-Fatigue scale was a 13-item self-administered questionnaire that assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means "not at all," and 4 means "very much." The FACIT-Fatigue scale score ranges from 0 to 52, with higher scores denoting lower levels of fatigue. A positive change from baseline score indicates an improvement.

Time frame: Baseline and Week 16

Percentage of Participants Who Achieve the European League Against Rheumatism (EULAR) Response Criteria Using CRP at Week 16

EULAR response criteria classify each participant as a good, moderate or non-responder to treatment based on the degree of improvement from baseline and the level of disease activity at the endpoint. EULAR response is derived using the individual subject's DAS28 as the measure of severity of disease. Good or moderate response is defined as follows: Good response: DAS28 at the time point ≤ 3.2 and improvement from baseline \> 1.2 Moderate response: DAS28 at the time point \> 3.2 and improvement from baseline \> 1.2, or DAS28 at the time point ≤ 5.1 and improvement from baseline \> 0.6 and ≤ 1.2

Time frame: Baseline and Week 16

Percentage of Participants With an American College of Rheumatology 50% Improvement (ACR 50) Response at Week 16

Percentage of participants with an American College of Rheumatology 50% Improvement (ACR50) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: * ≥ 50% improvement in 68 tender joint count; * ≥ 50% improvement in 66 swollen joint count; and * ≥ 50% improvement in at least 3 of the 5 following parameters: Subject's assessment of pain (measured on a 100 mm visual analog scale \[VAS\]); Subject's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index \[(HAQ-DI)\]); C-Reactive Protein.

Time frame: Baseline and Week 16

Percentage of Participants With an American College of Rheumatology 70% Improvement (ACR 70) Response at Week 16

Percentage of participants with an American College of Rheumatology 70% Improvement (ACR70) response. A participant was a responder if the following 3 criteria for improvement from baseline were met: * ≥ 70% improvement in 68 tender joint count; * ≥ 70% improvement in 66 swollen joint count; and * ≥ 70% improvement in at least 3 of the 5 following parameters: Subject's assessment of pain (measured on a 100 mm visual analog scale \[VAS\]); Subject's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (\[HAQ-DI\]); C-Reactive Protein

Time frame: Baseline and Week 16

Percentage of Participants With an American College of Rheumatology 50% Improvement (ACR 50) Response at Week 24

Percentage of participants with an American College of Rheumatology 50% Improvement (ACR 50) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: * ≥ 50% improvement in 68 tender joint count; * ≥ 50% improvement in 66 swollen joint count; and * ≥ 50% improvement in at least 3 of the 5 following parameters: Subject's assessment of pain (measured on a 100 mm visual analog scale \[VAS\]); Subject's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index \[(HAQ-DI)\]); C-Reactive Protein.

Time frame: Baseline and Week 24

Percentage of Participants With an American College of Rheumatology 70% Improvement (ACR 70) Response at Week 24

Percentage of participants with an American College of Rheumatology 70% Improvement (ACR 70) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: * ≥ 70% improvement in 68 tender joint count; * ≥ 70% improvement in 66 swollen joint count; and * ≥ 70% improvement in at least 3 of the 5 following parameters: Subject's assessment of pain (measured on a 100 mm visual analog scale \[VAS\]); Subject's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index \[(HAQ-DI)\]); C-Reactive Protein.

Time frame: Baseline and Week 24

Change From Baseline in the Medical Outcome Study Short Form 36-item (SF-36) Physical Functioning Domain at Week 24

The Medical Outcome Study Short Form 36-Item Health Survey, Version 2 (SF-36) is a self-administered instrument that measures the impact of disease on overall quality of life and consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). Norm-based scores were used in analyses, calibrated so that 50 is the average score and the standard deviation equals 10. Higher scores indicate a higher level of functioning. The physical functioning domain assesses limitations in physical activities because of health problems. A positive change from Baseline score indicates an improvement.

Time frame: Baseline and Week 24

Change From Baseline in the Clinical Disease Activity Index (CDAI) at Week 24

The Clinical Disease Activity Index (CDAI) is a composite index that is calculated as the sum of the: * 28 tender joint count (TJC), * 28 swollen joint count (SJC), * Subject's Global Assessment of Disease Activity measured on a 100 mm visual analog scale (VAS), where 0 mm = lowest disease activity and 100 mm = highest; * Physician's Global Assessment of Disease Activity -measured on a 100 mm VAS, where 0 mm = lowest disease activity and 100 mm = highest. The CDAI score ranges from 0-76 where lower scores indicate less disease activity.The following thresholds of disease activity have been defined for the CDAI: Remission: ≤ 2.8; Low Disease Activity: \> 2.8 and ≤ 10; Moderate Disease Activity: \> 10 and ≤ 22; High Disease Activity: \> 22

Time frame: Baseline and Week 24

Percentage of Participants Who Achieve Low Disease Activity or Remission Based on the Clinical Disease Activity Index (CDAI) ≤ 10 at Week 24

The Clinical Disease Activity Index (CDAI) is a composite index that is calculated as the sum of the: * 28 tender joint count (TJC), * 28 swollen joint count (SJC), * Subject's Global Assessment of Disease Activity measured on a 100 mm visual analog scale (VAS), where 0 mm = lowest disease activity and 100 mm = highest; * Physician's Global Assessment of Disease Activity -measured on a 100 mm VAS, where 0 mm = lowest disease activity and 100 mm = highest. The CDAI score ranges from 0-76 where lower scores indicate less disease activity.The following thresholds of disease activity have been defined for the CDAI: Remission: ≤ 2.8; Low Disease Activity: \> 2.8 and ≤ 10; Moderate Disease Activity: \> 10 and ≤ 22; High Disease Activity: \> 22

Time frame: Baseline and Week 24

Change From Baseline in Disease Activity Score 28 (DAS28) Using CRP at Week 24

The DAS28 measures the severity of disease at a specific time and is derived from the following variables: * 28 tender joint count * 28 swollen joint count, which do not include the DIP joints, the hip joint, or the joints below the knee; * C-reactive protein (CRP) * Subject's Global Assessment of Disease Activity. DAS28 values range from 2.0 to 10.0 while higher values mean a higher disease activity. A DAS28 score higher than 5.1 indicates high disease activity, a DAS28 score less than 3.2 indicates low disease activity, and a DAS28 score less than 2.6 indicates clinical remission.

Time frame: Baseline and Week 24

Percentage Change From Baseline in the Tender Joint Count at Week 24

Joint tenderness is the presence of pain in a joint when pressure is applied by the examiner to elicit tenderness. The 68 tender joint count evaluates the following joints: upper-temporomandibular, sternoclavicular, acromioclavicular, shoulder, elbow, wrist, meta-carpophalangeal, proximal interphalangeal and distal interphalangeal; lower: hip, knee, ankle, midtarsal, metatarsophalangeal and proximal interphalangeal.

Time frame: Baseline and Week 24

Percentage Change From Baseline in the Swollen Joint Count at Week 24

Joint swelling is soft tissue swelling that is detectable along the joint margins and is assessed by inspection and direct palpation of the joint, by the examiner. The ACR 66 swollen joint count evaluates the following joints: upper-temporomandibular, sternoclavicular, acromioclavicular, shoulder, elbow, wrist, metacarpophalangeal, proximal interphalangeal and distal interphalangeal; lower: knee, ankle, midtarsal, metatarsophalangeal and proximal interphalangeal.

Time frame: Baseline and Week 24

Percentage Change From Baseline in the Subject Assessment of Pain at Week 24

The Subject Assessment of Pain was measured asking the participant to place a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents "no pain," and the right-hand boundary (score = 100 mm) represents "pain as severe as can be imagined." The distance from the mark to the left-hand boundary was recorded in millimeters.

Time frame: Baseline and Week 24

Percentage Change From Baseline in the Subject Global Assessment of Disease Activity at Week 24

The Subject Global Assessment of Disease Activity was measured asking the participant to place a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents " lowest disease activity," and the right-hand boundary (score = 100 mm) represents " highest disease activity." The distance from the mark to the left-hand boundary was recorded in millimeters.

Time frame: Baseline and Week 24

Percentage Change From Baseline in the Physician Global Assessment of Disease Activity at Week 24

The Physician Global Assessment of Disease Activity was measured asking the physician to assess the subject's current arthritis disease activity by placing a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents " lowest disease activity," and the right-hand boundary (score = 100 mm) represents " highest disease activity." The distance from the mark to the left-hand boundary was recorded in millimeters.

Time frame: Baseline and Week 24

Percentage Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 24

The Health Assessment Questionnaire - Disability Index (HAQ-DI) was a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability.

Time frame: Baseline and Week 24

Percentage Change From Baseline in the High Sensitivity C-Reactive Protein (CRP) at Week 24

C-Reactive Protein (CRP) is a substance produced by the liver that increases in the presence of inflammation in the body. An elevated CRP level is identified with blood tests and is considered a non-specific "marker" for disease.

Time frame: Baseline and Week 24

Percentage Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at Week 24

The erythrocyte sedimentation rate (ESR) is a blood test that can reveal inflammatory activity. The subject's blood is placed in a tall, thin tube, red erythrocytes gradually settle to the bottom. Inflammation can cause the cells to clump together. Because these clumps of cells are denser than individual cells, they settle to the bottom more quickly. The ESR test measures the distance red blood cells fall in a test tube in one hour. The farther the red blood cells have descended, the greater the inflammatory response.

Time frame: Baseline and Week 24

Change From Baseline in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Score at Week 24

The FACIT-Fatigue scale was a 13-item self-administered questionnaire that assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means "not at all," and 4 means "very much." The FACIT-Fatigue scale score ranges from 0 to 52, with higher scores denoting lower levels of fatigue. A positive change from baseline score indicates an improvement.

Time frame: Baseline and Week 24

Percentage of Participants Who Achieve an Improvement of ≥ 0.22 Units From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 24

The Health Assessment Questionnaire - Disability Index (HAQ-DI) is a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability.

Time frame: Baseline and Week 24

Percentage of Participants Who Achieve an Improvement of at Least 4 Units From Baseline in the Functional Assessment of Chronic Illness Therapy -Fatigue (FACIT-Fatigue) at Week 24

The FACIT-Fatigue scale is a 13-item self-administered questionnaire that assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means "not at all," and 4 means "very much." The FACIT-Fatigue scale score ranges from 0 to 52, with higher scores denoting lower levels of fatigue. A positive change from baseline score indicates an improvement.

Time frame: Baseline and Week 24

Percentage of Participants Who Achieve the European League Against Rheumatism (EULAR) Response Criteria Using CRP at Week 24

EULAR response criteria classify each participant as a good, moderate or non-responder to treatment based on the degree of improvement from baseline and the level of disease activity at the endpoint. EULAR response is derived using the individual subject's DAS28 as the measure of severity of disease. Good or moderate response is defined as follows: Good response: DAS28 at the time point ≤ 3.2 and improvement from baseline \> 1.2 Moderate response: DAS28 at the time point \> 3.2 and improvement from baseline \> 1.2, or DAS28 at the time point ≤ 5.1 and improvement from baseline \> 0.6 and ≤ 1.2

Time frame: Baseline and Week 24

Percentage of Participants With an American College of Rheumatology 20% Improvement (ACR 20) Response at Week 52

Percentage of participants with an American College of Rheumatology 20% Improvement (ACR 20) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: * ≥ 20% improvement in 68 tender joint count; * ≥ 20% improvement in 66 swollen joint count; and * ≥ 20% improvement in at least 3 of the 5 following parameters: Subject's assessment of pain (measured on a 100 mm visual analog scale \[VAS\]); Subject's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (\[HAQ-DI\]); C-Reactive Protein.

Time frame: Baseline and Week 52

Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) at Week 52

The Health Assessment Questionnaire - Disability Index (HAQ-DI) was a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability.

Time frame: Baseline and Week 52

Change From Baseline in the Medical Outcome Study Short Form 36-item (SF-36) Physical Functioning Domain at Week 52

The Medical Outcome Study Short Form 36-Item Health Survey, Version 2 (SF-36) is a self-administered instrument that measures the impact of disease on overall quality of life and consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). Norm-based scores were used in analyses, calibrated so that 50 is the average score and the standard deviation equals 10. Higher scores indicate a higher level of functioning. The physical functioning domain assesses limitations in physical activities because of health problems. A positive change from Baseline score indicates an improvement.

Time frame: Baseline and Week 52

Change From Baseline in the Clinical Disease Activity Index (CDAI) at Week 52

The Clinical Disease Activity Index (CDAI) is a composite index that is calculated as the sum of the: * 28 tender joint count (TJC), * 28 swollen joint count (SJC), * Subject's Global Assessment of Disease Activity measured on a 100 mm visual analog scale (VAS), where 0 mm = lowest disease activity and 100 mm = highest; * Physician's Global Assessment of Disease Activity -measured on a 100 mm VAS, where 0 mm = lowest disease activity and 100 mm = highest. The CDAI score ranges from 0-76 where lower scores indicate less disease activity. The following thresholds of disease activity have been defined for the CDAI: Remission: ≤ 2.8; Low Disease Activity: \> 2.8 and ≤ 10; Moderate Disease Activity: \> 10 and ≤ 22; High Disease Activity: \> 22

Time frame: Baseline and Week 52

Percentage of Participants Who Achieve Low Disease Activity or Remission Based on the Clinical Disease Activity Index (CDAI) ≤ 10 at Week 52

The Clinical Disease Activity Index (CDAI) is a composite index that is calculated as the sum of the: * 28 tender joint count (TJC), * 28 swollen joint count (SJC), * Subject's Global Assessment of Disease Activity measured on a 100 mm visual analog scale (VAS),, where 0 mm = lowest disease activity and 100 mm = highest; * Physician's Global Assessment of Disease Activity -measured on a 100 mm VAS, where 0 mm = lowest disease activity and 100 mm = highest. The CDAI score ranges from 0-76 where lower scores indicate less disease activity. The following thresholds of disease activity have been defined for the CDAI: Remission: ≤ 2.8; Low Disease Activity: \> 2.8 and ≤ 10; Moderate Disease Activity: \> 10 and ≤ 22; High Disease Activity: \> 22

Time frame: Baseline and Week 52

Change From Baseline in the Disease Activity Score 28 (DAS 28) Using CRP at Week 52

The DAS28 measures the severity of disease at a specific time and is derived from the following variables: * 28 tender joint count (TJC28) * 28 swollen joint count (SJC28), which do not include the distal interphalangeal (DIP) joints, the hip joint, or the joints below the knee; * C-reactive protein (CRP) * Subject's global assessment of disease activity (SGA). DAS28 values range from 2.0 to 10.0 while higher values mean a higher disease activity. A DAS28 score higher than 5.1 indicates high disease activity, a DAS28 score less than 3.2 indicates low disease activity, and a DAS28 score less than 2.6 indicates clinical remission.

Time frame: Baseline and Week 52

Percentage Change From Baseline in the Tender Joint Count at Week 52

Joint tenderness is the presence of pain in a joint when pressure is applied by the examiner to elicit tenderness. The 68 tender joint count evaluates the following joints: upper-temporomandibular, sternoclavicular, acromioclavicular, shoulder, elbow, wrist, meta-carpophalangeal, proximal interphalangeal and distal interphalangeal; lower: hip, knee, ankle, midtarsal, metatarsophalangeal and proximal interphalangeal.

Time frame: Baseline and Week 52

Percentage Change From Baseline in the Swollen Joint Count at Week 52

Joint swelling is soft tissue swelling that is detectable along the joint margins and is assessed by inspection and direct palpation of the joint, by the examiner. The ACR 66 swollen joint count evaluates the following joints: upper-temporomandibular, sternoclavicular, acromioclavicular, shoulder, elbow, wrist, metacarpophalangeal, proximal interphalangeal and distal interphalangeal; lower: knee, ankle, midtarsal, metatarsophalangeal and proximal interphalangeal.

Time frame: Baseline and Week 52

Percentage Change From Baseline in the Subject Assessment of Pain at Week 52

The Subject Assessment of Pain was measured asking the participant to place a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents "no pain," and the right-hand boundary (score = 100 mm) represents "pain as severe as can be imagined." The distance from the mark to the left-hand boundary was recorded in millimeters.

Time frame: Baseline and Week 52

Percentage Change From Baseline in the Subject Global Assessment of Disease Activity at Week 52

The Subject Global Assessment of Disease Activity was measured asking the participant to place a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents " lowest disease activity," and the right-hand boundary (score = 100 mm) represents " highest disease activity." The distance from the mark to the left-hand boundary was recorded in millimeters.

Time frame: Baseline and Week 52

Percentage Change From Baseline in the Physician Global Assessment of Disease Activity at Week 52

The Physician Global Assessment of Disease Activity was measured asking the physician to assess the subject's current arthritis disease activity by placing a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents " lowest disease activity," and the right-hand boundary (score = 100 mm) represents " highest disease activity." The distance from the mark to the left-hand boundary was recorded in millimeters.

Time frame: Baseline and Week 52

Percentage Change From Baseline in the Health Assessment Questionnaire - Disability Index (HAQ-DI) Score at Week 52

The Health Assessment Questionnaire - Disability Index (HAQ-DI) was a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability.

Time frame: Baseline and Week 52

Percentage Change From Baseline in the High Sensitivity C-Reactive Protein (CRP) at Week 52

C-Reactive Protein (CRP) is a substance produced by the liver that increases in the presence of inflammation in the body. An elevated CRP level is identified with blood tests and is considered a non-specific "marker" for disease.

Time frame: Baseline and Week 52

Percentage Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at Week 52

The erythrocyte sedimentation rate (ESR) is a blood test that can reveal inflammatory activity. The subject's blood is placed in a tall, thin tube, red erythrocytes gradually settle to the bottom. Inflammation can cause the cells to clump together. Because these clumps of cells are denser than individual cells, they settle to the bottom more quickly. The ESR test measures the distance red blood cells fall in a test tube in one hour. The farther the red blood cells have descended, the greater the inflammatory response.

Time frame: Baseline and Week 52

Change From Baseline in the FACIT-Fatigue Scale Score at Week 52

The FACIT-Fatigue scale was a 13-item self-administered questionnaire that assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means "not at all," and 4 means "very much." The FACIT-Fatigue scale score ranges from 0 to 52, with higher scores denoting lower levels of fatigue. A positive change from baseline score indicates an improvement.

Time frame: Baseline and Week 52

Percentage of Participants Who Achieve an Improvement of ≥ 0.22 Units From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 52

The Health Assessment Questionnaire - Disability Index (HAQ-DI) was a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability.

Time frame: Baseline and Week 52

Percentage of Participants With an American College of Rheumatology 50% Improvement (ACR 50) Response at Week 52

Percentage of participants with an American College of Rheumatology 50% Improvement (ACR 50) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: * ≥ 50% improvement in 68 tender joint count; * ≥ 50% improvement in 66 swollen joint count; and * ≥ 50% improvement in at least 3 of the 5 following parameters: Subject's assessment of pain (measured on a 100 mm visual analog scale \[VAS\]); Subject's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index \[(HAQ-DI)\]); C-Reactive Protein.

Time frame: Baseline and Week 52

Percentage of Participants With an American College of Rheumatology 70% Improvement (ACR 70) Response at Week 52

Percentage of participants with an American College of Rheumatology 70% Improvement (ACR 70) response. A participant was a responder if the following 3 criteria for improvement from baseline were met: * ≥ 70% improvement in 68 tender joint count; * ≥ 70% improvement in 66 swollen joint count; and * ≥ 70% improvement in at least 3 of the 5 following parameters: Subject's assessment of pain (measured on a 100 mm visual analog scale \[VAS\]); Subject's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (\[HAQ-DI\]); C-Reactive Protein

Time frame: Baseline and Week 52

Percentage of Participants Who Achieve an Improvement of at Least 4 Units From Baseline in the Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) at Week 52

The FACIT-Fatigue scale is a 13-item self-administered questionnaire that assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means "not at all," and 4 means "very much." The FACIT-Fatigue scale score ranges from 0 to 52, with higher scores denoting lower levels of fatigue. A positive change from baseline score indicates an improvement.

Time frame: Baseline and Week 52

Percentage of Participants Who Achieve the European League Against Rheumatism (EULAR) Response Criteria Using CRP at Week 52

The EULAR response criteria classify each subject as a good, moderate or non-responder to treatment based on the degree of improvement from baseline and the level of disease activity at the endpoint. EULAR response is derived using the individual subject's DAS28 as the measure of severity of disease. Good or moderate response is defined as follows: Good response: DAS28 at the time point ≤ 3.2 and improvement from baseline \> 1.2 Moderate response: DAS28 at the time point \> 3.2 and improvement from baseline \> 1.2, or DAS28 at the time point ≤ 5.1 and improvement from baseline \> 0.6 and ≤ 1.2

Time frame: Baseline and Week 52

Percentage of Participants With an American College of Rheumatology 20% Improvement (ACR 20) Response at Year 2

Percentage of participants with an American College of Rheumatology 20% Improvement (ACR 20) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: * ≥ 20% improvement in 68 tender joint count; * ≥ 20% improvement in 66 swollen joint count; and * ≥ 20% improvement in at least 3 of the 5 following parameters: Subject's assessment of pain (measured on a 100 mm visual analog scale \[VAS\]); Subject's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (\[HAQ-DI\]); C-Reactive Protein. The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.

Time frame: Baseline and Year 2

Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) at Year 2

The Health Assessment Questionnaire - Disability Index (HAQ-DI) is a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability. The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.

Time frame: Baseline and Year 2

Change From Baseline in the Medical Outcome Study Short Form 36-item (SF-36) Physical Functioning Domain at Year 2

The Medical Outcome Study Short Form 36-Item Health Survey, Version 2 (SF-36) was a self-administered instrument that measures the impact of disease on overall quality of life and consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). The concepts measured by the SF-36 are not specific to any age, disease, or treatment group, allowing comparison of relative burden of different diseases and the relative benefit of different treatments. Norm-based scores were used in analyses, calibrated so that 50 is the average score and the standard deviation equals 10. Higher scores indicate a higher level of functioning. The physical functioning domain assesses limitations in physical activities because of health problems. A positive change from baseline score indicates an improvement. The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.

Time frame: Baseline and Year 2

Change From Baseline in the Clinical Disease Activity Index (CDAI) at Year 2

The Clinical Disease Activity Index (CDAI) is a composite index that is calculated as the sum of the: * 28 tender joint count (TJC), * 28 swollen joint count (SJC), * Subject's Global Assessment of Disease Activity measured on a 10 mm visual analog scale (VAS), where 0 mm = lowest disease activity and 10 mm = highest; * Physician's Global Assessment of Disease Activity -measured on a 10 mm VAS, where 0 mm = lowest disease activity and 10 mm = highest. The CDAI score ranges from 0-76 where lower scores indicate less disease activity. The following thresholds of disease activity have been defined for the CDAI: Remission: ≤ 2.8 Low Disease Activity: \> 2.8 and ≤ 10 Moderate Disease Activity: \> 10 and ≤ 22 High Disease Activity: \> 22 The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.

Time frame: Baseline and Year 2

Percentage of Participants Who Achieve Low Disease Activity or Remission Based on the Clinical Disease Activity Index (CDAI) ≤ 10 at Year 2

The Clinical Disease Activity Index (CDAI) is a composite index that is calculated as the sum of the: * 28 tender joint count (TJC), * 28 swollen joint count (SJC), * Subject's Global Assessment of Disease Activity measured on a 10 mm visual analog scale (VAS), where 0 mm = lowest disease activity and 10 mm = highest; * Physician's Global Assessment of Disease Activity -measured on a 10 mm VAS, where 0 mm = lowest disease activity and 10 mm = highest. The CDAI score ranges from 0-76 where lower scores indicate less disease activity. The following thresholds of disease activity have been defined for the CDAI: Remission: ≤ 2.8 Low Disease Activity: \> 2.8 and ≤ 10 Moderate Disease Activity: \> 10 and ≤ 22 High Disease Activity: \> 22 The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.

Time frame: Baseline and Year 2

Change From Baseline in Disease Activity Score 28 (DAS28) (Using C-Reactive Protein) (CRP) at Year 2

The DAS 28 measures the severity of disease at a specific time and is derived from the following variables: * 28 tender joint count (TJC28) * 28 swollen joint count (SJC28), which do not include the distal interphalangeal (DIP) joints, the hip joint, or the joints below the knee; * C-reactive protein (CRP) * Subject's global assessment of disease activity (SGA ). A DAS28 score higher than 5.1 indicates high disease activity, a DAS28 score less than 3.2 indicates low disease activity, and a DAS28 score less than 2.6 indicates clinical remission. DAS28 values range from 2.0 to 10.0 while higher values mean a higher disease activity. The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.

Time frame: Baseline and Year 2

Percentage Change From Baseline in the Individual American College of Rheumatology Components at Year 2

The Individual ACR Components were defined as follows: 1. Tender Joint Count (out of 68 joints) 2. Swollen Joint Count (out of 66 joints) 3. Subject Assessment of Pain (0 to 100 mm VAS) 4. Subject Global Assessment of Disease Activity (0 to 100 mm VAS) 5. Physician Global Assessment of Disease Activity (0 to 100 mm VAS) 6. HAQ-DI Score 7. Acute Phase Reactant High Sensitivity C-Reactive Protein (hsCRP, mg/dL) Erythrocyte Sedimentation Rate (ESR) The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.

Time frame: Baseline and Year 2

Change From Baseline in the Functional Assessment of Chronic Illness Therapy -Fatigue (FACIT-Fatigue) at Year 2

The FACIT-Fatigue scale is a 13-item self-administered questionnaire that assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means "not at all," and 4 means "very much." The FACIT-Fatigue scale score ranges from 0 to 52, with higher scores denoting lower levels of fatigue. A positive change from baseline score indicates an improvement. The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.

Time frame: Baseline and Year 2

Percentage of Participants Who Achieve an Improvement of ≥ 0.22 Units From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) at Year 2

The Health Assessment Questionnaire - Disability Index (HAQ-DI) was a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability. The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.

Time frame: Baseline and Year 2

Percentage of Participants With an American College of Rheumatology 50% Improvement (ACR 50) Response at Year 2

Percentage of participants with an American College of Rheumatology 50% Improvement (ACR 50) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: * ≥ 50% improvement in 68 tender joint count; * ≥ 50% improvement in 66 swollen joint count; and * ≥ 50% improvement in at least 3 of the 5 following parameters: Subject's assessment of pain (measured on a 100 mm visual analog scale \[VAS\]); Subject's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index \[(HAQ-DI)\]); C-Reactive Protein. The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.

Time frame: Baseline and Year 2

Percentage of Participants With an American College of Rheumatology 70% Improvement (ACR 70) Response at Year 2

Percentage of participants with an American College of Rheumatology 70% Improvement (ACR 70) response. A participant was a responder if the following 3 criteria for improvement from baseline were met: * ≥ 70% improvement in 68 tender joint count; * ≥ 70% improvement in 66 swollen joint count; and * ≥ 70% improvement in at least 3 of the 5 following parameters: Subject's assessment of pain (measured on a 100 mm visual analog scale \[VAS\]); Subject's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (\[HAQ-DI\]); C-Reactive Protein The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.

Time frame: Baseline and Year 2

Percentage of Participants Who Achieve an Improvement of at Least 4 Units From Baseline in the Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) at Year 2

The FACIT-Fatigue scale was a 13-item self-administered questionnaire that assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means "not at all," and 4 means "very much." The FACIT-Fatigue scale score ranges from 0 to 52, with higher scores denoting lower levels of fatigue. The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.

Time frame: Baseline and Year 2

Percentage of Participants Who Achieve the European League Against Rheumatism (EULAR) Response Criteria Using CRP at Year 2

EULAR response criteria classify each participant as a good, moderate or non-responder to treatment based on the degree of improvement from baseline and the level of disease activity at the endpoint. EULAR response is derived using the individual subject's DAS28 as the measure of severity of disease. Good or moderate response is defined as follows: Good response: DAS28 at the time point ≤ 3.2 and improvement from baseline \> 1.2 Moderate response: DAS28 at the time point \> 3.2 and improvement from baseline \> 1.2, or DAS28 at the time point ≤ 5.1 and improvement from baseline \> 0.6 and ≤ 1.2 The study was terminated before the 2-year time point was reached due to lack of clinical efficacy.

Time frame: Baseline and Year 2