Trial Outcomes & Findings for 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 (NCT NCT01578850)

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).

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.

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

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

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

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

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

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

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

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.

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.

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

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.

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.

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.

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.

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.

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.

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.

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.

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.

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'.

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'.

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'.

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'.

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'.

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'.

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.

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.

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.

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.